Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oligodendrocytes play a crucial role in creating the myelin sheath that is an important component in neural transmission. In an animal model of transient cerebral ischemia, application of oligodendrocyte progenitor cells (OPCs) has not yet been reported. In this study, the effects of F3.Olig2 transplantation on memory and cognitive dysfunction were investigated in the aged gerbil in which ischemic stroke was induced. To investigate the possible mechanisms underlying repair, changes in the expression of myelin basic protein (MBP), oligodendrocyte-specific protein (OSP), and brain-derived neurotrophic factor (BDNF) were examined. Experimental ischemic stroke was induced by occlusion of bilateral common carotid arteries in aged gerbils. Gerbils (n=31 per group) were randomly divided into three groups: (1) vehicle sham group, (2) vehicle ischemia group, and (3) F3.Olig2 ischemia group. After 1, 3, and 7 days of ischemiareperfusion (I-R), saline or F3.Olig2 cells (1106 cells in 100 l) were injected into the gerbils intravenously. The gerbils were sacrificed 10 days after I-R for identification of grafted F3.Olig2 cells, and 15 and 30 days after I-R for tissue analysis after conducting passive avoidance and novel object recognition test. Injected F3.Olig2 cells and MBP, OSP, and BDNF were detected by specific antibodies using immunohistochemistry and/or Western blots. Memory and cognition were significantly increased in the F3.Olig2 ischemia group compared with the vehicle ischemia group. In the F3.Olig2 ischemia group, the neurons were not protected from ischemic damage; however, MBP, OSP, and BDNF expressions were significantly increased. Our results show that injection of F3.Olig2 cells significantly improved impaired memory and cognition, which might be related to increased MBP expression via increasing OSP and BDNF expression in the aged gerbil hippocampus following transient cerebral ischemia.
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PMID:Intravenously Infused F3.Olig2 Improves Memory Deficits via Restoring Myelination in the Aged Hippocampus Following Experimental Ischemic Stroke. 2744 84

Because stroke therapies are still limited and patients are often concerned by long-term sequelae with significant impairment of daily living, elaborated neuroprotective strategies are needed. During the last decades, research substantially improved the knowledge on cellular pathologies responsible for stroke-related tissue damage. In this context, the neurovascular unit (NVU) concept has been established, summarizing the affections of neurons, associated astrocytes and the vasculature. Although oligodendrocytes were already identified to play a major role in other brain pathologies, their role during stroke evolution and long-lasting tissue damage is poorly understood. This study aims to explore oligodendrocyte structures, i.e., oligodendrocytes and their myelin-associated proteins, after experimental focal cerebral ischemia. For translational issues, different ages and genotypes including an Alzheimer-like background were considered to mimic potential co-morbidities. Three- and 12-month-old wild-type and triple-transgenic mice were subjected to unilateral middle cerebral artery occlusion. Immunofluorescence labeling was performed on forebrain tissues affected by 24 h of ischemia to visualize the oligodendrocyte-specific protein (OSP), the myelin basic protein (MBP), and the neuron-glia antigen 2 (NG2) with reference to the ischemic lesion. Subsequent analyses concomitantly detected the vasculature and the 2', 3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) to consider the NVU concept and to explore the functional relevance of histochemical data on applied oligodendrocyte markers. While the immunosignal of NG2 was found to be nearly absent 24 h after ischemia onset, enhanced immunoreactivities for OSP and especially MBP were observed in close regional association to the vasculature. Added quantitative analyses based on inter-hemispheric differences of MBP-immunoreactivity revealed a shell-like pattern with a significant increase directly in the ischemic core, followed by a gradual decline toward the striatum, the ischemic border zone and the lateral neocortex. This observation was consistent in subsequent analyses on the potential impact of age and genetic background. Furthermore, immunoreactivities for CNPase, MBP, and OSP were found to be simultaneously enhanced. In conclusion, this study provides evidence for a critical role of oligodendrocyte structures in the early phase after experimental stroke, strengthening their involvement in the ischemia-affected NVU. Consequently, oligodendrocytes and their myelin-associated proteins may qualify as potential targets for neuroprotective and regenerative approaches in stroke.
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PMID:Immunosignals of Oligodendrocyte Markers and Myelin-Associated Proteins Are Critically Affected after Experimental Stroke in Wild-Type and Alzheimer Modeling Mice of Different Ages. 2946 21

The contribution of the inwardly rectifying K+ channel subtype Kir4.1 has been focused mainly on astrocytes, where they play important roles in the maintenance of resting membrane potential, extracellular K+ uptake, and facilitation of glutamate uptake in the central nervous system. Here, we report the role of Kir4.1 channels in NG2-glia during brain development, potassium signaling, and in an ischemic stroke disease model. Kir4.1 channels are widely expressed in NG2-glia during brain development. In the adult mouse hippocampus, Kir4.1 channels in NG2-glia constitute more than 80% of K+ channels inward currents. This large portion of Kir4.1 channel currents exhibits a deficit in NG2-glia as an initial response in a transient ischemic mouse model. Further evidence indicates that Kir4.1 deficits in NG2-glia potentially cause axonal myelin loss in ischemia through the association with oligodendrocyte-specific protein (OSP/Claudin-11), which unravels a potential therapeutic target in the treatment of ischemic stroke.
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PMID:Kir4.1 channels in NG2-glia play a role in development, potassium signaling, and ischemia-related myelin loss. 3027 61