Endothelial progenitor cells and revascularization following stroke

Feifei Ma, Anna Morancho, Joan Montaner, Anna Rosell

Abstract
Brain injury after ischemia induces the mobilization of endothelial progenitor cells (EPCs), a population of bone marrow-derived cells with angio-vasculogenic capabilities. These cells have been also tested in pre-clinical models and proposed for neurorepair therapy aiming to treat patients in the delayed phases of stroke disease. Promising results in the pre-clinical field encourage the translation into a clinical therapeutic approach. In this review, we will describe EPCs actions for enhanced revascularization and neurorepair, which on one hand are by their direct incorporation into new vascular networks/structures or by direct cell–cell interactions with other brain cells, but also to indirect cell–cell communication thorough EPCs secreted growth factors. All these actions contribute to potentiate neurovascular remodeling and neurorepair. The data presented in this review encourages for a deep understanding of the mechanisms of the cross-talks between EPCs and other brain and progenitor cells, which deserves additional investigations and efforts that may lead to new EPCs-based therapies for stroke patients.

Source: CLICK HERE

Keywords:
Stroke, Endothelial progenitor cell, Growth factor, Angiogenesis, Vasculogenesis, Neurorepair

Mechanisms of cell–cell interaction in oligodendrogenesis and remyelination after stroke

Kanako Itoh, Takakuni Maki, Josephine Lok, Ken Arai

Abstract

White matter damage is a clinically important aspect of several central nervous system diseases, including stroke. Cerebral white matter primarily consists of axonal bundles ensheathed with myelin secreted by mature oligodendrocytes, which play an important role in neurotransmission between different areas of gray matter. During the acute phase of stroke, damage to oligodendrocytes leads to white matter dysfunction through the loss of myelin. On the contrary, during the chronic phase, white matter components promote an environment, which is favorable for neural repair, vascular remodeling, and remyelination. For effective remyelination to take place, oligodendrocyte precursor cells (OPCs) play critical roles by proliferating and differentiating into mature oligodendrocytes, which help to decrease the burden of axonal injury. Notably, other types of cells contribute to these OPC responses under the ischemic conditions. This mini-review summarizes the non-cell autonomous mechanisms in oligodendrogenesis and remyelination after white matter damage, focusing on how OPCs receive support from their neighboring cells.

Source: CLICK HERE

Keywords:

White matter, Stroke, Oligodendrocyte precursor cell, Cell–cell interaction

The axon–glia unit in white matter stroke: Mechanisms of damage and recovery

Shira Rosenzweig, S. Thomas Carmichael

Abstract

Approximately one quarter of all strokes in humans occur in white matter, and the progressive nature of white matter lesions often results in severe physical and mental disability. Unlike cortical grey matter stroke, the pathology of white matter stroke revolves around disrupted connectivity and injured axons and glial cells, rather than neuronal cell bodies. Consequently, the mechanisms behind ischemic damage to white matter elements, the regenerative responses of glial cells and their signaling pathways, all differ significantly from those in grey matter. Development of effective therapies for white matter stroke would require an enhanced understanding of the complex cellular and molecular interactions within the white matter, leading to the identification of new therapeutic targets. This review will address the unique properties of the axon–glia unit during white matter stroke, describe the challenging process of promoting effective white matter repair, and discuss recently-identified signaling pathways which may hold potential targets for repair in this disease.

Source: CLICK HERE

Keywords:

White matter, Stroke, Ischemia, Repair, Oligodendrocytes, Myelin

The evolving roles of pericyte in early brain injury after subarachnoid hemorrhage

Yujie Chen, Qiang Li, Jiping Tang, Hua Feng, John H Zhang

Abstract

Despite accumulated understanding on the mechanisms of early brain injury and improved management of subarachnoid hemorrhage (SAH), it is still one of the serious and refractory health problems around the world. Traditionally, pericyte, served as capillary contraction handler, is recently considered as the main participant of microcirculation regulation in SAH pathophysiology. However, accumulate evidences indicate that pericyte is much more than we already know. Therefore, we briefly review the characteristics, regulation pathways and functions of pericyte, aim to summarize the evolving new pathophysiological roles of pericyte that are implicated in early brain injury after SAH and to improve our understanding in order to explore potential novel therapeutic options for patients with SAH.

Source: CLICK HERE

Keywords:

Pericyte, Subarachnoid hemorrhage, Early brain injury, Vascular neural network

Intercellular cross-talk in intracerebral hemorrhage

Yusuke Egashira, Ya Hua, Richard F. Keep, Guohua Xi

Abstract

Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high mortality and morbidity. Currently, there are few treatment strategies for ICH-induced brain injury. A recent increase in interest in the pathophysiology of ICH has led to elucidation of the pathways underlying ICH-induced brain injury, pathways where intercellular and hematoma to cell signaling play important roles. In this review, we summarize recent advances in ICH research focusing on intercellular and hematoma:cell cross-talk related to brain injury and recovery after ICH.

Source: CLICK HERE

Keywords:

Brain injury, Experimental model, Intracerebral hemorrhage, Injury mechanism, Intercellular signaling

Cellular connections, microenvironment and brain angiogenesis in diabetes: Lost communication signals in the post-stroke period

Adviye Ergul, John Paul Valenzuela, Abdelrahman Y. Fouda, Susan C. Fagan

Abstract

Diabetes not only increases the risk but also worsens the motor and cognitive recovery after stroke, which is the leading cause of disability worldwide. Repair after stroke requires coordinated communication among various cell types in the central nervous system as well as circulating cells. Vascular restoration is critical for the enhancement of neurogenesis and neuroplasticity. Given that vascular disease is a major component of all complications associated with diabetes including stroke, this review will focus on cellular communications that are important for vascular restoration in the context of diabetes.

Source: CLICK HERE

Keywords:

Diabetes, Angiogenesis, Vascular restoration, Stroke

SIRP/CD47 signaling in neurological disorders

Haiyue Zhanga, Fengwu Li, Yuanyuan Yang, Jun Chena, Xiaoming Hu

Abstract

Microglia play important roles in the process of neuronal injury and recovery. Numeous surface receptors have been described to regulate microglial activation. These receptors tightly mediate normal microglial functions including cell mobility, phagocytosis, and production of inflammatory mediators or trophic factors. In recent years, significant progresses have been achieved for understanding the signaling mechanisms underlying these receptors. Their specific roles in neurological diseases have been documented. This review will focus on the signal regulatory protein (SIRP) and its ligand CD47, two surface receptors expressed on microglia and other cells in the central nervous system (CNS) such as neurons. We will discuss the involvement of SIRP/CD47 signaling in microglial activation and in the interplay between microglia and other CNS cells. Current studies reveal the importance of CD47 and SIRPα in the process of neuroinflammation in the CNS disorders. The dual and contradictory role of CD47 suggests that targeting the SIRPα/CD47 signaling may achieve different effects depending on disease stage.

Source: CLICK HERE

Keywords:

Signal regulatory protein (SIRP), CD47, Microglia, Neuroinflammation

Interaction of astrocytes and T cells in physiological and pathological conditions

Luokun Xie, Shao-Hua Yang

Abstract

The central nervous system (CNS) has long been recognized as a site of ‘immune privilege’ because of the existence of the blood brain barrier (BBB) which presumably isolates CNS from the peripheral immunosurveillance. Different from the peripheral organs, CNS is unique in response to all forms of CNS injury and disease which is mainly mediated by resident microglia and astrocyte. There is increasing evidence that immune cells are not only involved in neuroinflammation process but also the maintenance of CNS homeostasis. T cells, an important immune cell population, are involved in the pathogenesis of some neurological diseases by inducing either innate or adaptive immune responses. Astrocytes, which are the most abundant cell type in the CNS, maintain the integrity of BBB and actively participate in the initiation and progression of neurological diseases. Surprisingly, how astrocytes and T cells interact and the consequences of their interaction are not clear. In this review we briefly summarized T cells diversity and astrocyte function. Then, we examined the evidence for the astrocytes and T cells interaction under physiological and pathological conditions including ischemic stroke, multiple sclerosis, viral infection, and Alzheimer’s disease.

Source: CLICK HERE

Keywords:

T cells, Astrocyte, Central nervous system, Stroke, Alzheimer’s disease, Multiple sclerosis

Complexity of the cell–cell interactions in the innate immune response after cerebral ischemia

Maria I. Cuartero, Ivan Ballesteros, Ignacio Lizasoain, Maria A. Moro

Abstract

In response to brain ischemia a cascade of signals leads to the activation of the brain innate immune system and to the recruitment of blood borne derived cells to the ischemic tissue. These processes have been increasingly shown to play a role on stroke pathogenesis. Here, we discuss the key features of resident microglia and different leukocyte subsets implicated in cerebral ischemia with special emphasis of neutrophils, monocytes and microglia. We focus on how leukocytes are recruited to injured brain through a complex interplay between endothelial cells, platelets and leukocytes and describe different strategies used to inhibit their recruitment. Finally, we discuss the possible existence of different leukocyte subsets in the ischemic tissue and the repercussion of different myeloid phenotypes on stroke outcome. The knowledge of the nature of these heterogeneous cell–cell interactions may open new lines of investigation on new therapies to promote protective immune responses and tissue repair after cerebral ischemia or to block harmful responses.

Source: CLICK HERE

Keywords:

Neuroinflammation, Stroke, Cerebral ischemia, Leukocyte, Microglia, Neuroimmune, Interactions

Matrix metalloproteinases as therapeutic targets for stroke

Yi Yang, Gary A. Rosenberg

Abstract

Matrix metalloproteinases (MMPs) are important in injury and recovery in ischemic injury. They are proteolytic enzymes that degrade all components of the extracellular matrix (ECM). They are secreted in a latent form, protecting the cell from damage, but once activated induce injury prior to rapid inactivation by four tissue inhibitors to metalloproteinases (TIMPs). Normally the constitutive enzymes, MMP-2 and membrane type MMP (MMP-14), are activated in a spatially specific manner and act close to the site of activation, while the inducible enzymes, MMP-3 and MMP-9, become active through the action of free radicals and other enzymes during neuroinflammation. Because of the complex nature of the interactions with tissues during development, injury and repair, the MMPs have multiple roles, participating in the injury process in the early stages and contributing to recovery during the later stages. This dual role complicates the planning of treatment strategies.

Source: CLICK HERE

Keywords:

Matrix metalloproteinases, Blood–brain barrier, Hypoxia/ischemia, Recovery, Angiogenesis

Collaterals: Implications in cerebral ischemic diseases and therapeutic interventions

Yasuo Nishijima, Yosuke Akamatsu, Phillip R. Weinstein, Jialing Liu

Abstract

Despite the tremendous progress made in the treatment of cerebrovascular occlusive diseases, many patients suffering from ischemic brain injury still experience dismal outcomes. Although rehabilitation contributes to post-stroke functional recovery, there is no doubt that interventions that promote the restoration of blood supply are proven to minimize ischemic injury and improve recovery. In response to the acutely decreased blood perfusion during arterial occlusion, arteriogenesis, the compensation of blood flow through the collateral circulation during arterial obstructive diseases can act not only in a timely fashion but also much more efficiently compared to angiogenesis, the sprouting of new capillaries, and a mechanism occurring in a delayed fashion while increases the total resistance of the vascular bed of the affected territory. Interestingly, despite the vast differences between the two vascular remodeling mechanisms, some crucial growth factors and cytokines involved in angiogenesis are also required for arteriogenesis. Understanding the mechanisms underlying vascular remodeling after ischemic brain injury is a critical step towards the development of effective therapies for ischemic stroke. The present article will discuss our current views in vascular remodeling acutely after brain ischemia, namely arteriogenesis, and some relevant clinical therapies available on the horizon in augmenting collateral flow that hold promise in treating ischemic brain injury.

Source: CLICK HERE

Keywords:

Arteriogenesis, Angiogenesis, Stroke, Carotid disease, Anastomosis, Vascular remodeling

Cerebral microvascular pericytes and neurogliovascular signaling in health and disease

Turgay Dalkara, Luis Alarcon-Martinez

Abstract

Increases in neuronal activity cause an enhanced blood flow to the active brain area. This neurovascular coupling is regulated by multiple mechanisms: Adenosine and lactate produced as metabolic end-products couple activity with flow by inducing vasodilation. As a specific mechanism to the brain, synaptic activity-induced Ca2+ increases in astrocytes, interneurons and neurons translate neuronal activity to vasoactive signals such as arachidonic acid metabolites and NO. K+ released onto smooth muscle cells through Ca2+-activated K+ channels on end-feet can also induce vasodilation during neuronal activity. An intense communication between the endothelia, pericytes and astrocytes is required for development and functioning of the neurovascular unit as well as the BBB. The ratio of pericytes to endothelial cells is higher in the cerebral microcirculation than other tissues. Pericytes play a role in distribution of microvascular blood flow in response to the local demand as a final regulatory step after arterioles, which feed a larger cohort of cells. Pericyte–endothelial communication is essential for vasculogenesis. Pericyte also take part in leukocyte infiltration and immune responses. The microvascular injury induced by ischemia/reperfusion plays a critical role in tissue survival after recanalization by inducing sustained pericyte contraction and microcirculatory clogging (no-reflow) and by disrupting BBB integrity. Suppression of oxidative/nitrative stress or sustained adenosine delivery during re-opening of an occluded artery improves the outcome of recanalization by promoting microcirculatory reflow. Pericyte dysfunction in retinal microvessels is the main cause of diabetic retinopathy. Recent findings suggest that the age-related microvascular dysfunction may initiate the neurodegenerative changes seen Alzheimer׳s dementia.

Source: CLICK HERE

Keywords:

Neurovascular unit, Neurovascular coupling, Pericyte, Angiogenesis, Inflammation Recanalization, Retinopathy, Dementia

Effect of acute stretch injury on action potential and network activity of rat neocortical neurons in culture

George C. Magou, Bryan J. Pfister, Joshua R. Berlin

Abstract

The basis for acute seizures following traumatic brain injury (TBI) remains unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical neurons that could underlie seizure activity, but studying initiating events causing hyperexcitability is difficult in these models. In vitro models of stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile investigation of cellular changes after injury but they have only demonstrated post-injury hypoexcitability. The goal of this study was to determine if neuronal hyperexcitability could be triggered by in vitro stretch injury. Controlled uniaxial stretch injury was delivered to a spatially delimited region of a spontaneously active network of cultured rat cortical neurons, yielding a region of stretch-injured neurons and adjacent regions of non-stretched neurons that did not directly experience stretch injury. Spontaneous electrical activity was measured in non-stretched and stretch-injured neurons, and in control neuronal networks not subjected to stretch injury. Non-stretched neurons in stretch-injured cultures displayed a three-fold increase in action potential firing rate and bursting activity 30–60 min post-injury. Stretch-injured neurons, however, displayed dramatically lower rates of action potential firing and bursting. These results demonstrate that acute hyperexcitability can be observed in non-stretched neurons located in regions adjacent to the site of stretch injury, consistent with reports that seizure activity can arise from regions surrounding the site of localized brain injury. Thus, this in vitro procedure for localized neuronal stretch injury may provide a model to study the earliest cellular changes in neuronal function associated with acute post-traumatic seizures.

Source: CLICK HERE

Keywords:

Traumatic brain injury, Hyperexcitability, Hypoexcitability, Action potential, Bursting activity, Current clamp technique

Changes in VGLUT2 expression and function in pain-related supraspinal regions correlate with the pathogenesis of neuropathic pain in a mouse spared nerve injury model

Zhi-Tong Wang, Gang Yu, Hong-Sheng Wang, Shou-Pu Yi, Rui-Bin Su, Ze-Hui Gong

Abstract

Vesicular glutamate transporters (VGLUTs) control the storage and release of glutamate, which plays a critical role in pain processing. The VGLUT2 isoform has been found to be densely distributed in the nociceptive pathways in supraspinal regions, and VGLUT2-deficient mice exhibit an attenuation of neuropathic pain; these results suggest a possible involvement of VGLUT2 in neuropathic pain. To further examine this, we investigated the temporal changes in VGLUT2 expression in different brain regions as well as changes in glutamate release from thalamic synaptosomes in spared nerve injury (SNI) mice. We also investigated the effects of a VGLUT inhibitor, Chicago Sky Blue 6B (CSB6B), on pain behavior, c-Fos expression, and depolarization-evoked glutamate release in SNI mice. Our results showed a significant elevation of VGLUT2 expression up to postoperative day 1 in the thalamus, periaqueductal gray, and amygdala, followed by a return to control levels. Consistent with the changes in VGLUT2 expression, SNI enhanced depolarization-induced glutamate release from thalamic synaptosomes, while CSB6B treatment produced a concentration-dependent inhibition of glutamate release. Moreover, intracerebroventricular administration of CSB6B, at a dose that did not affect motor function, attenuated mechanical allodynia and c-Fos up-regulation in pain-related brain areas during the early stages of neuropathic pain development. These results demonstrate that changes in the expression of supraspinal VGLUT2 may be a new mechanism relevant to the induction of neuropathic pain after nerve injury that acts through an aggravation of glutamate imbalance.

Source: CLICK HERE

Keywords:

Neuropathic pain, VGLUT2, Supraspinal brain regions, Thalamus, Glutamate release, Chicago Sky Blue 6B

Temporal profile of the vascular anatomy evaluated by 9.4-tesla magnetic resonance angiography and histological analysis in mice with the R4859K mutation of RNF213, the susceptibility gene for moyamoya disease

Atsushi Kanoke, Miki Fujimura, Kuniyasu Niizuma, Akira Ito, Hiroyuki Sakata, Mika Sato-Maeda, Yuiko Morita-Fujimura, Shigeo Kure, Teiji Tominaga

Abstract

Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an unknown etiology. Recent genome-wide and locus-specific association studies identified the RNF213 gene (RNF213) as an important susceptibility gene of MMD among East Asian populations; however, the mechanism by which an abnormality in RNF213 leads to MMD has not yet been elucidated. Therefore, we herein generated Rnf213-knock-in mice (RNF213-KI) expressing a missense mutation in mouse Rnf213, p. R4828K, on Exon 61, corresponding to human RNF213, p. R4859K, on Exon 60, in MMD patients, and investigated whether they developed MMD. We assessed the temporal profile of intracranial arteries by 9.4-T magnetic resonance angiography (MRA) continuously in the same mouse up to 64 weeks of age. The ratios of the outer diameter of the internal carotid artery (ICA)/basilar artery (BA) and middle cerebral artery (MCA)/BA were evaluated histopathologically. The common carotid arteries (CCA) were sectioned and arterial wall thickness/thinness was evaluated by Elastica-Masson staining before and after CCA ligation, which selectively induced vascular hyperplasia. The results obtained showed that RNF213-KI grew normally, with no significant difference being observed in MRA findings or the anatomy of the circle of Willis between homozygous RNF213-KI and wild-type (Wt) littermates. Furthermore, no significant difference was noted in the diameter of the intracranial vasculature (ICA/BA; p=0.82, MCA/BA; p=0.27) or in vascular remodeling after CCA ligation. Therefore, RNF213-KI did not spontaneously develop MMD. Multiple secondary insults such as environmental factors may contribute to the onset of MMD in addition to genetic factors.

Source: CLICK HERE

Keywords:

Moyamoya disease, RNF213, Knock-in mice, Magnetic resonance angiography (MRA)

Intranasal administration of human umbilical cord mesenchymal stem cells-conditioned medium enhances vascular remodeling after stroke

Qiuchen Zhao, Jinxia Hu, Jie Xiang, Yuming Gu, Peisheng Jin, Fang Hu, Zunsheng Zhang, Yonghai Liu, Kun Zan, Zuohui Zhang, Jie Zu, Xinxin Yang, Hongjuan Shi, Jienan Zhu, Yun Xu, Guiyun Cui, Xinchun Ye

Abstract

Stem cell-based treatments have been reported to be a potential strategy for stroke. However, tumorigenic potential and low survival rates of transplanted cells could attenuate the efficacy of the stem cell-based treatments. The application of stem cell-condition medium (CM) may be a practicable approach to conquer these limitations. In this study, we investigated whether intranasal administration of human umbilical cord mesenchymal stem cells (hUCMSCs)-CM has the therapeutic effects in rats after stroke. Adult male rats were subjected to middle cerebral artery occlusion (MCAo) and were treated by intranasal routine with or without hUCMSCs-CM (1 ml/kg/d), starting 24 h after MCAo and daily for 14 days. Neurological functional tests, blood brain barrier (BBB) leakage, were measured. Angiogenesis and angiogenic factor expression were measured by immunohistochemistry, and Western blot, respectively. hUCMSCs-CM treatment of stroke by intranasal routine starting 24 h after MCAo in rats significantly enhances BBB functional integrity and promotes functional outcome but does not decrease lesion volume compared to rats in DMEM/F12 medium control group and saline control group. Treatment of ischemic rats with hUCMSCs-CM by intranasal routine also significantly decreases the levels of Ang2 and increases the levels of both Ang1 and Tie2 in the ischemic brain. To take together, increased expression of Ang1 and Tie2 and decreased expression of Ang2, induced by hUCMSCs-CM treatment, contribute to vascular remodeling in the ischemic brain which plays an important role in functional outcome after stroke.

Source: CLICK HERE

Keywords:

Intranasal administration, Human umbilical cord mesenchymal stem cells, Conditioned medium, Angiopoietin, Vascular remodeling

The mature/pro nerve growth factor ratio is decreased in the brain of diabetic rats: Analysis by ELISA methods

Marzia Soligo, Virginia Protto, Fulvio Florenzano, Luisa Bracci-Laudiero, Fabrizio De Benedetti, Antonio Chiaretti, Luigi Manni

Abstract

Nerve growth factor (NGF) is essential for the survival and functional maintenance of forebrain cholinergic neurons projecting mainly to the cortex and hippocampus. NGF is produced in these brain areas but while mature NGF (mNGF) has a survival/differentiative effect its precursor proNGF elicits apoptosis in cholinergic neurons. Impaired neurotransmission, loss of cholinergic phenotype and abnormal NGF content characterize the cholinergic circuitries in animal models of diabetic encephalopathy (DE). It is not known whether defective production or maturation of NGF could play a key role in cholinergic neurodegeneration in DE. Quantification of the mNGF/proNGF ratio is therefore needed to characterize the development and progression of NGF-related neuronal diseases. In our work, we aimed at developing ELISA methods to measure either mNGF or proNGF tissue concentration; and to define the mNGF/proNGF ratio in the rat cortex and hippocampus during the early stage of streptozotocin-induced type 1 diabetes. Using commercially available NGF ELISA kits and antibodies, we set up ELISAs for human and rat mNGF and proNGF. We then analyzed the mNGF/proNGF ratio in the cortex and hippocampus of DE rats and found that it decreased in both tissues starting from the fourth week after diabetes induction. In diabetic brain the increase in proNGF involves accumulation of the isoforms with molecular weights of 50 and 34 kDa. Our study for the first time specifically quantifies the absolute content of mature and proNGF and the mNGF/proNGF ratio in brain tissues, suggesting that early progression of experimental DE is characterized by defective maturation of NGF.

Source: CLICK HERE

Keywords:

Nerve growth factor, proNGF, Diabetic encephalopathy, ELISA, Cholinergic system, Rat

Atypical cortical gyrification in adolescents with histories of heavy prenatal alcohol exposure

M. Alejandra Infante, Eileen M. Moore, Amanda Bischoff-Grethe, Robyn Migliorini, Sarah N. Mattson, Edward P. Riley

Abstract

Prenatal alcohol exposure can adversely affect brain development, although little is known about the effects of prenatal alcohol exposure on gyrification. Gyrification reflects cortical folding complexity and is a process by which the surface of the brain creates sulci and gyri. Prior studies have shown that prenatal alcohol exposure is associated with reduced gyrification in childhood, but no studies have examined adolescents. Subjects (12–16 years) comprised two age-equivalent groups: 30 adolescents with histories of heavy prenatal alcohol exposure (AE) and 19 non-exposed controls (CON). A T1-weighted image was obtained for all participants. Local gyrification index (LGI) was estimated using FreeSurfer. General linear models were used to determine between group differences in LGI controlling for age and sex. Age-by-group interactions were also investigated while controlling for sex. The AE group displayed reduced LGI relative to CON in the bilateral superior parietal region, right postcentral region, and left precentral and lateral occipital regions (ps<.001). Significant age-by-group interactions were observed in the right precentral and lateral occipital regions, and in the left pars opercularis and inferior parietal regions (ps<.01). The AE group showed age-related reductions in gyrification in all regions whereas the CON group showed increased gyrification with age in the lateral occipital region only. While cross-sectional, the age-related reduction in gyrification observed in the AE group suggests alterations in cortical development throughout adolescence and provides further insight into the pathophysiology and brain maturation of adolescents prenatally exposed to alcohol.

Source: CLICK HERE

Keywords:

Fetal alcohol spectrum disorders (FASD), Fetal alcohol syndrome (FAS), Prenatal alcohol exposure, Gyrification, Local gyrification index (LGI), Structural MRI

CysLT2 receptor mediates lipopolysaccharide-induced microglial inflammation and consequent neurotoxicity in vitro

Lu Chen, Yi Yang, Chen-Tan Li, Si-Ran Zhang, Wei Zheng, Er-Qing Wei, Li-Hui Zhang

Abstract

Neuroinflammation induced by microglial activation plays a critical role in many neurodegenerative diseases, including Parkinson׳s disease (PD). Recent studies have indicated that cysteinyl leukotriene receptor 2 (CysLT2R) is involved in inflammation and brain injury after cerebral ischemia. However, the role of CysLT2R in microglial responses associated with PD remains unclear. In the present study, we determined the regulatory roles of CysLT2R in microglial inflammation and subsequent neurotoxicity in an in vitro brain inflammation model induced by the microglial activator lipopolysaccharide (LPS). We found that LPS induced phagocytosis of a murine microglial cell line (BV-2 cells) and increased production of the proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β). The expression of CysLT2R protein was up-regulated and the nuclear translocation of CysLT2R was induced in LPS-activated BV-2 cells. CysLT2R selective antagonist HAMI 3379 significantly inhibited LPS-induced phagocytosis and overproduction of the cytokines in BV-2 cells. Similarly, the CysLT2R silencing by specific short hairpin RNA (shRNA) had the same effects as those of HAMI 3379, suggesting that the effect might be CysLT2R-dependent. Furthermore, the conditioned medium (CM) derived from LPS-treated BV-2 cells induced the cell death of a rat adrenal pheochromocytoma cell line (PC12). HAMI 3379 and CysLT2R shRNA attenuated neuronal death by suppressing the production of neurotoxic cytokines released from LPS-activated microglia. Collectively, these results suggest that CysLT2R mediates LPS-induced microglial inflammation and consequent neurotoxicity. CysLT2R may be a promising molecular target that modulates microglia-related neuroinflammation in neurodegenerative disorders, such as PD.

Source: CLICK HERE

Keywords:

Microglia, Inflammation, Neurotoxicity, Cysteinyl leukotriene receptor 2, Antagonist, RNA interference

S-nitrosoglutathione reduces tau hyper-phosphorylation and provides neuroprotection in rat model of chronic cerebral hypoperfusion

Je-Seong Won, Balasubramaniam Annamalai, Seungho Choi, Inderjit Singh, Avtar K. Singh

Abstract

We have previously reported that treatment of rats subjected to permanent bilateral common carotid artery occlusion (pBCCAO), a model of chronic cerebral hypoperfusion (CCH), with S-nitrosoglutathione (GSNO), an endogenous nitric oxide carrier, improved cognitive functions and decreased amyloid-β accumulation in the brains. Since CCH has been implicated in tau hyperphosphorylation induced neurodegeneration, we investigated the role of GSNO in regulation of tau hyperphosphorylation in rat pBCCAO model. The rats subjected to pBCCAO had a significant increase in tau hyperphosphorylation with increased neuronal loss in hippocampal/cortical areas. GSNO treatment attenuated not only the tau hyperphosphorylation, but also the neurodegeneration in pBCCAO rat brains. The pBCCAO rat brains also showed increased activities of GSK-3β and Cdk5 (major tau kinases) and GSNO treatment significantly attenuated their activities. GSNO attenuated the increased calpain activities and calpain-mediated cleavage of p35 leading to production of p25 and aberrant Cdk5 activation. In in vitro studies using purified calpain protein, GSNO treatment inhibited calpain activities while 3-morpholinosydnonimine (a donor of peroxynitrite) treatment increased its activities, suggesting the opposing role of GSNO vs. peroxynitrite in regulation of calpain activities. In pBCCAO rat brains, GSNO treatment attenuated the expression of inducible nitric oxide synthase (iNOS) expression and also reduced the brain levels of nitro-tyrosine formation, thereby indicating the protective role of GSNO in iNOS/nitrosative-stress mediated calpain/tau pathologies under CCH conditions. Taken together with our previous report, these data support the therapeutic potential of GSNO, a biological NO carrier, as a neuro- and cognitive-protective agent under conditions of CCH.

Source: CLICK HERE

Keywords:

Calpain, Cdk5, Chronic cerebral hypoperfusion, S-nitrosoglutathione, p25, tau

Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication

Takafumi Nakano, Keiichi Irie, Kazuhide Hayakawa, Kazunori Sano, Yoshihiko Nakamur, Masayoshi Tanaka, Yuta Yamashita, Tomomitsu Satho, Masayuki Fujioka, Carl Muroi, Koichi Matsuo, Hiroyasu Ishikura, Kojiro Futagami, Kenichi Mishima

Abstract

Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1 mg/kg) or tPA (10 mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24 h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke.

Source: CLICK HERE

Keywords:

ADAMTS13, Tissue plasminogen activator, Cerebral ischemic stroke, Therapeutic time window, Hemorrhagic complication

Suppressed expression of cystathionine β-synthase and smaller cerebellum in Wistar Kyoto rats

Mao Nagasawa, Hiromi Ikeda, Takahiro Kawase, Ayaka Iwamoto, Shinobu Yasuo, Mitsuiro Furuse

 Abstract

We previously reported that Wistar Kyoto rats, an animal model of depression, have a characteristically abnormal serine metabolism in the brain, i.e., lower serine and cystathionine, which is a metabolite of serine, concentrations in the brain. To explore the mechanism underlying this abnormality, the expression of cystathionine β-synthase and serine racemase, which are the enzymes involved in the serine metabolism, was investigated in the cerebellum and hippocampus of Wistar and Wistar Kyoto rats. Wistar Kyoto rats exhibited a significantly lower mRNA expression of cystathionine β-synthase in the cerebellum in comparison with Wistar rats, while expression levels in the hippocampus did not differ between strains. Previous study indicated that the reduction of cystathionine β-synthase in the brain induced cerebellar aplasia in mice. Therefore, the cerebellar size was compared between Wistar rats and Wistar Kyoto rats. Wistar Kyoto rats displayed a lower ratio of cerebellum weight to whole-brain weight compared with Wistar rats of the same generation or similar body weight, suggesting that Wistar Kyoto rats exhibit smaller cerebellum. These results suggest that the lower mRNA expression of cystathionine β-synthase in the cerebellum and the smaller size of cerebellum may be related to the depression-like behavior in Wistar Kyoto rats.

Source: CLICK HERE

Keywords:

Cystathionine β-synthase, Serine racemase, Wistar Kyoto rats, Cerebellum

Rosiglitazone attenuates early brain injury after experimental subarachnoid hemorrhage in rats

Chi Gu, Yifei Wang, Jianru Li, Jingyin Chen, Feng Yan, Cheng Wu, Gao Chen

Abstract

Early brain injury (EBI) plays a crucial role in the pathological progress of subarachnoid hemorrhage (SAH). This study was designed to determine whether rosiglitazone protects the brain against EBI in rats, and discuss the role of the anti-apoptotic mechanism mediated by Bcl-2 family proteins in this neuroprotection. 86 male Sprague-Dawley rats were divided into the sham group, the SAH+ vehicle group and the SAH+ rosiglitazone group. SAH was induced via an endovascular perforation technique and rosiglitazone (3 mg/kg) or vehicle was administered. Mortality, neurological scores, brain water content, Evans blue dye assay, TUNEL stain assay, Gelatin zymography, and western blot analysis were performed. Rosiglitazone significantly improved mortality, neurological scores, brain water content, blood brain barrier (BBB) and apoptosis compared with the vehicle group within 24 h after SAH. The TUNEL staining assay demonstrated that apoptosis was ameliorated. Cleaved Caspase-3 and MMP-9 expression was reduced, whereas Bcl-2 and p-Bad was markedly preserved by rosiglitazone. A significant elevation of p-Akt was detected after rosiglitazone treatment. Our study demonstrated that rosiglitazone plays a neuroprotective role in EBI after SAH via attenuation of BBB disruption, brain edema and apoptosis.

Source: CLICK HERE

Keywords:

Subarachnoid hemorrhage, Early brain injury, PPARγ, Apoptosis, Bcl-2, Akt pathway

Neuroprotective effects of 3-O-demethylswertipunicoside against MPTP-induced Parkinson׳s disease in vivo and its antioxidant properties in vitro

Jun-Jun Zhou, Shen-Yu Zhai, Hui-Nan Zhang, Yue-Hua Wang, Xiao-Ping Pu

Abstract

3-O-demethylswertipunicoside (3-ODS) has been reported to protect dopaminergic neurons against neurotoxicity induced by 1-methyl-4-phenylpyridinium (MPP+) in PC12 cells. Here, we investigate the neuroprotective effects in vivo and antioxidant activities in vitro of 3-ODS. In the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated mouse model of Parkinson׳s disease (PD), 3-ODS dose-dependently improved motor coordination (as shown by rotarod test), increased the contents of dopamine (DA) and its metabolites in the striatum, and increased the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN). In addition, 3-ODS also increased the spine density in hippocampal CA1 neurons. In antioxidant assays, 3-ODS showed a strong capacity in scavenging hydroxyl radical, superoxide anion and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical in a concentration-dependent manner. Taken together, we conclude that 3-ODS attenuates the PD-related motor deficits mainly through its neuroprotective effects, growth-promoting effects on spine density, and its antioxidant activities.

Source: CLICK HERE

Keywords:

3-O-demethylswertipunicoside, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, Parkinson׳s disease, Neuroprotection, Growth-promoting effect, Antioxidant activity

Effect of sparteine on status epilepticus induced in rats by pentylenetetrazole, pilocarpine and kainic acid

Fridha Villalpando-Vargas, Laura Medina-Ceja

Abstract

The long-term effects of status epilepticus (SE) include severe clinical conditions that result in disorders of various organs and systems as well as neurological damage that could lead to death. Sparteine is a quinolizidine alkaloid synthesized from most Lupine species, and its anticonvulsive effect was evaluated in the pentylenetetrazole model of SE. However, efforts to clearly determine the anticonvulsive effect of sparteine have not been made previously. For this reason, we consider it important to study the anticonvulsant effects of sparteine at the level of behavior and EEG activity in three different SE models. The animals of the control groups, which received intraperitoneal pentylenetetrazole (90 mg/kg), kainic acid (9 mg/kg) or pilocarpine (370 mg/kg), exhibited convulsive behavior and epileptiform activity. After sparteine pretreatment (13 mg/kg, administered 30 min before the convulsive drug), the animals administered pentylenetetrazole and pilocarpine exhibited reduced mortality rates compared with the corresponding control groups, while the animals administered kainic acid exhibited a delayed onset of convulsive behavior and decreased seizure duration compared with the corresponding control group. In the three models of SE, a significant reduction in the amplitude and frequency of discharge trains was observed. These results support the anticonvulsant effect of low doses of sparteine and allow us to direct our efforts to other new anticonvulsant strategies for seizure treatment. However, it is necessary to perform more experiments to determine the precise mechanism through which sparteine produces an anticonvulsant effect at this concentration.

Source: CLICK HERE

Keywords:

Kainic acid, Pentylenetetrazole, Pilocarpine, Seizures, Sparteine, Status epilepticus

Preserved dichotomy but highly irregular and burst discharge in the basal ganglia in alert dystonic rats at rest

Deepak Kumbharea, Kunal D. Chaniary, Mark S. Baron

Abstract

Despite its prevalence, the underlying pathophysiology of dystonia remains poorly understood. Using our novel tri-component classification algorithm, extracellular neuronal activity in the globus pallidus (GP), STN, and the entopeduncular nucleus (EP) was characterized in 34 normal and 25 jaundiced dystonic Gunn rats with their heads restrained while at rest. In normal rats, neurons in each nucleus were similarly characterized by two physiologically distinct types: regular tonic with moderate discharge frequencies (mean rates in GP, STN and EP ranging from 35–41 spikes/s) or irregular at slower frequencies (17–20 spikes/s), with a paucity of burst activity. In dystonic rats, these nuclei were also characterized by two distinct principal neuronal patterns. However, in marked difference, in the dystonic rats, neurons were primarily slow and highly irregular (12–15 spikes/s) or burst predominant (14–17 spikes/s), with maintained modest differences between nuclei. In GP and EP, with increasing severity of dystonia, burstiness was moderately further increased, irregularity mildly further increased, and discharge rates mildly further reduced. In contrast, these features did not appreciably change in STN with worsening dystonia. Findings of a lack of bursting in GP, STN and EP in normal rats in an alert resting state and prominent bursting in dystonic Gunn rats suggest that cortical or other external drive is normally required for bursting in these nuclei and that spontaneous bursting, as seen in dystonia and Parkinson׳s disease, is reflective of an underlying pathophysiological state. Moreover, the extent of burstiness appears to most closely correlate with the severity of the dystonia.

Source: CLICK HERE

Keywords:

Basal ganglia, Neurophysiology, Dystonia, Dichotomy

Galectin-1 suppresses methamphetamine induced neuroinflammation in human brain microvascular endothelial cells: Neuroprotective role in maintaining blood brain barrier integrity

Neil U. Parikh, R. Aalinkeel, J.L. Reynolds, B.B. Nair, D.E. Sykes, M.J. Mammen, S.A. Schwartz, S.D. Mahajan

Abstract

Methamphetamine (Meth) abuse can lead to the breakdown of the blood–brain barrier (BBB) integrity leading to compromised CNS function. The role of Galectins in the angiogenesis process in tumor-associated endothelial cells (EC) is well established; however no data are available on the expression of Galectins in normal human brain microvascular endothelial cells and their potential role in maintaining BBB integrity. We evaluated the basal gene/protein expression levels of Galectin-1, -3 and -9 in normal primary human brain microvascular endothelial cells (BMVEC) that constitute the BBB and examined whether Meth altered Galectin expression in these cells, and if Galectin-1 treatment impacted the integrity of an in-vitro BBB. Our results showed that BMVEC expressed significantly higher levels of Galectin-1 as compared to Galectin-3 and -9. Meth treatment increased Galectin-1 expression in BMVEC. Meth induced decrease in TJ proteins ZO-1, Claudin-3 and adhesion molecule ICAM-1 was reversed by Galectin-1. Our data suggests that Galectin-1 is involved in BBB remodeling and can increase levels of TJ proteins ZO-1 and Claudin-3 and adhesion molecule ICAM-1 which helps maintain BBB tightness thus playing a neuroprotective role. Galectin-1 is thus an important regulator of immune balance from neurodegeneration to neuroprotection, which makes it an important therapeutic agent/target in the treatment of drug addiction and other neurological conditions.

Source: CLICK HERE

Keywords:

Methamphetamine, Galectin-1, Human brain microvascular endothelial cells, Blood brain barrier, Tight junctions, Oxidative stress, Proinflammatory cytokines, Transendothelial electrical resistance

Social factors modulate restraint stress induced hyperthermia in mice

Shigeru Watanabe

Abstract

Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress.

Source: CLICK HERE

Keywords:

Restraint stress, Social factors, Empathy, Social inequality, Hyperthermia

Astaxanthin reduces matrix metalloproteinase-9 expression and activity in the brain after experimental subarachnoid hemorrhage in rats

Xiang-Sheng Zhang, Xin Zhang, Qing-Rong Zhang, Qi Wu, Wei Li, Tian-Wei Jiang, Chun-Hua Hang

Abstract

We have previously shown that astaxanthin (ATX) reduces the blood–brain barrier (BBB) disruption and neurovascular dysfunction following subarachnoid hemorrhage (SAH) insults. However, the underlying mechanisms remain unclear. It is known that the matrix metalloproteinases (MMPs), especially matrix metalloproteinase-9 (MMP-9) plays a crucial role in the pathogenesis of secondary brain injury after SAH. And ATX has the ability to regulate MMP-9 in other models. Herein, we investigated whether ATX could ameliorate MMP-9 activation and expression in a rat model of SAH. A total of 144 rats were randomly divided into the following groups: control group (n=36), SAH group (n=36), SAH+vehicle group (n=36), and SAH+ATX group (n=36). The SAH model was induced by injection of 0.3 ml autologous blood into the prechiasmatic cistern. ATX (20 μl of 0.1 mmol) or vehicle was administered intracerebroventricularly 30 min after SAH induction. Mortality, neurological function, brain edema and blood–brain barrier (BBB) permeability were measured at 24 and 72 h after SAH. Biochemical and zymographic methods were used to analyze MMP-9 expression and activity in brain samples. Immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining were also evaluated at 24 h. Our data indicated that ATX could significantly reduce the expression and activity of MMP-9, leading to the amelioration of brain edema, BBB impairment, neurological deficits and TUNEL-positive cells at 24 h but not 72 h after SAH. The ATX-mediated down-regulation of MMP-9 was correlated with the decreased levels of IL-1β, TNF-α, oxidative stress, activated microglia and infiltrating neutrophils. These results suggest that the neurovascular protection of ATX in SAH is partly associated with the inhibition of MMP-9 expression and activity.

Source: CLICK HERE

Keywords:

Astaxanthin, Subarachnoid hemorrhage, Early brain injury, Matrix metalloproteinase-9

Depletion of macrophages in CD11b diphtheria toxin receptor mice induces brain inflammation and enhances inflammatory signaling during traumatic brain injury

Ryan A. Frielera, b, Sameera Nadimpallia, Lauren K. Bolanda, Angela Xiea, Laura J. Kooistra, Jianrui Song, Yutein Chung, Kae W. Cho, Carey N. Lumeng,  Michael M. Wang,  Richard M. Mortensena

Abstract

Immune cells have important roles during disease and are known to contribute to secondary, inflammation-induced injury after traumatic brain injury. To delineate the functional role of macrophages during traumatic brain injury, we depleted macrophages using transgenic CD11b-DTR mice and subjected them to controlled cortical impact. We found that macrophage depletion had no effect on lesion size assessed by T2-weighted MRI scans 28 days after injury. Macrophage depletion resulted in a robust increase in proinflammatory gene expression in both the ipsilateral and contralateral hemispheres after controlled cortical impact. Interestingly, this sizeable increase in inflammation did not affect lesion development. We also showed that macrophage depletion resulted in increased proinflammatory gene expression in the brain and kidney in the absence of injury. These data demonstrate that depletion of macrophages in CD11b-DTR mice can significantly modulate the inflammatory response during brain injury without affecting lesion formation. These data also reveal a potentially confounding inflammatory effect in CD11b-DTR mice that must be considered when interpreting the effects of macrophage depletion in disease models.

Source: CLICK HERE

Keywords:

Macrophage depletion, CD11b-DTR, Traumatic brain injury, Inflammation

miR-29c regulates NAV3 protein expression in a transgenic mouse model of Alzheimer׳s disease

Yuanyuan Zong, Pin Yu, Hongxia Cheng, Hailin Wang, Xiaoying Wang, Chunlian Liang, Hua Zhu, Yejun Qin, Chuan Qin

Abstract

The microRNA-29 family (miRNA-29s) has three mature members, miR-29a, miR-29b and miR-29c, which have been implicated in the regulation of the pathogenesis of Alzheimer׳s disease (AD). The miR-29 family members exhibit differential regulation in various diseases and different subcellular distribution. In the present study, we initially investigated differential expression of miR-29c in the hippocampus and the frontal cortex of the young APPswe/PSΔE9 mouse brain, accompanied by inverse expression of neurone navigator 3 (NAV3), a regulator of axon guidance. We observed that miR-29c directly mediated downregulation of NAV3 protein expression in vitro. The mouse NAV3 mRNA has a functional miR-29c binding site in the 3′ UTR, which localized in the position between 830–836 bp of 3′UTR region, slightly different from human NAV3 mRNA binding site. These observations suggest that miR-29c may be involved in neurodegenerative processes by regulating NAV3 expression in the young AD mouse.

Source: CLICK HERE

Keywords:

miR-29c, Alzheimer׳s disease, NAV3 protein, microRNAs, APPswe/PSΔE9 mice 

Evaluative conditioning of positive and negative valence affects P1 and N1 in verbal processing

Lars Kuchinke, Nathalie Fritsch, Christina J. Muller

Abstract

The present study examined the effect of contextual learning on the neural processing of previously meaningless pseudowords. During an evaluative conditioning session on 5 consecutive days, participants learned to associate 120 pseudowords with either positive, neutral or negative pictures. In a second session, participants were presented all conditioned pseudowords again together with 40 new pseudowords in a recognition memory task while their event-related potentials (ERPs) were recorded. The behavioral data confirm successful learning of pseudoword valence. At the neural level, early modulations of the ERPs are visible at the P1 and the N1 components discriminating between positively and negatively conditioned pseudowords. Differences to new pseudowords were visible at later processing stages as indicated by modulations of the LPC. These results support a contextual learning hypothesis that is able to explain very early emotional ERP modulations in visual word recognition. Source localization indicates a role of medial-frontal brain regions as a likely origin of these early valence discrimination signals which are discussed to promote top-down signals to sensory processing.

Source: CLICK HERE

Keywords:

Evaluative conditioning, ERP, Positive valence, Negative valence, Pseudowords

Hippocampal NMDA receptors are involved in rats spontaneous object recognition only under high memory load condition

Manami Sugita, Kazuo Yamada, Natsumi Iguchi, Yukio Ichitani

Abstract

The possible involvement of hippocampal N-methyl-d-aspartate (NMDA) receptors in spontaneous object recognition was investigated in rats under different memory load conditions. We first estimated rats׳ object memory span using 3–5 objects in “Different Objects Task (DOT)” in order to confirm the highest memory load condition in object recognition memory. Rats were allowed to explore a field in which 3 (3-DOT), 4 (4-DOT), or 5 (5-DOT) different objects were presented. After a delay period, they were placed again in the same field in which one of the sample objects was replaced by another object, and their object exploration behavior was analyzed. Rats could differentiate the novel object from the familiar ones in 3-DOT and 4-DOT but not in 5-DOT, suggesting that rats׳ object memory span was about 4. Then, we examined the effects of hippocampal AP5 infusion on performance in both 2-DOT (2 different objects were used) and 4-DOT. The drug treatment before the sample phase impaired performance only in 4-DOT. These results suggest that hippocampal NMDA receptors play a critical role in spontaneous object recognition only when the memory load is high.

Source: CLICK HERE

Keywords:

Hippocampus, NMDA receptors, Spontaneous object recognition, Memory load, Rats

Resisting false recognition: An ERP study of lure discrimination

Alexa M. Morcom

Abstract

There is keen interest in what enables rememberers to differentiate true from false memories and which strategies are likely to be the most effective. This study measured electrical brain activity while healthy young adults performed a mnemonic discrimination task, deciding whether color pictures had been studied, were similar to studied pictures (lures), or were new. Between 500 and 800 ms post-stimulus, event-related potentials (ERPs) for correctly recognized studied pictures and falsely recognized lures compared to those for correctly rejected novel items had a left centroparietal scalp distribution. This was typical of the parietal old/new effect associated with recollection, and in line with previous evidence that similar lures may elicit false or phantom recollection as opposed to just familiarity. There was no evidence of a parietal effect for correctly rejected lures as would be expected if recall-to-reject was used. The ERP old/new effects for lures also varied with individual differences in performance. Parietal effects for falsely recognized lures were larger in better performers, who successfully rejected a greater number of lures as “similar”. The better performers also showed more pronounced right frontocentral old/new effects between 800 and 1100 ms for correctly rejected and falsely recognized similar lures. The enhancement of false recollection in better performers implies false recognition of lures occurred only when more specific information was recovered about the study episodic. Together, the findings suggest reliance on recollection to decide that items were studied, supported by post-retrieval processing.

Source: CLICK HERE

Keywords:

Episodic memory, False memory, Recognition, Recollection, ERPs, Retrieval, Retrieval monitoring