title: Long-term survival and regeneration of neuronal and vasculature cells inside the core region after ischemic stroke in adult mice.
abstract: Focal cerebral ischemia results in an ischemic core surrounded by the peri-infarct region (penumbra). Most research attention has been focused on penumbra while the pattern of cell fates inside the ischemic core is poorly defined. In the present investigation, we tested the hypothesis that, inside the ischemic core, some neuronal and vascular cells could survive the initial ischemic insult while regenerative niches might exist many days after stroke in the adult brain. Adult mice were subjected to focal cerebral ischemia induced by permanent occlusion of distal branches of the middle cerebral artery (MCA) plus transient ligations of bilateral common carotid artery (CCA). The ischemic insult uniformly reduced the local cerebral blood flow (LCBF) by 90%. Massive cell death occurred due to multiple mechanisms and a significant infarction was cultivated in the ischemic cortex 24 h later. Nevertheless, normal or even higher levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) persistently remained in the core tissue, some NeuN-positive and Glut-1/College IV-positive cells with intact ultrastructural features resided in the core 7-14 days post stroke. BrdU-positive but TUNEL-negative neuronal and endothelial cells were detected in the core where extensive extracellular matrix infrastructure developed. Meanwhile, GFAP-positive astrocytes accumulated in the penumbra and Iba-1-positive microglial/macrophages invaded the core several days after stroke. The long term survival of neuronal and vascular cells inside the ischemic core was also seen after a severe ischemic stroke induced by permanent embolic occlusion of the MCA. We demonstrate that a therapeutic intervention of pharmacological hypothermia could save neurons/endothelial cells inside the core. These data suggest that the ischemic core is an actively regulated brain region with residual and newly formed viable neuronal and vascular cells acutely and chronically after at least some types of ischemic strokes.
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA.
authors: Michael Qize
authors: MQ
authors: Jiang
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA.|Department of Neurology, Friendship Hospital, Capital Medical University, Beijing, China.
authors: Ying-Ying
authors: YY
authors: Zhao
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA.
authors: Wenyuan
authors: W
authors: Cao
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA.|Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affair Medical Center, Decatur, GA.
authors: Zheng Zachory
authors: ZZ
authors: Wei
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA.|Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affair Medical Center, Decatur, GA.
authors: Xiaohuan
authors: X
authors: Gu
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA.|Department of Neurology, Friendship Hospital, Capital Medical University, Beijing, China.
authors: Ling
authors: L
authors: Wei
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA.|Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affair Medical Center, Decatur, GA.
authors: Shan Ping
authors: SP
authors: Yu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D020520:Brain Infarction / Q000000981:diagnostic imaging / Q000209:etiology; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000473:pathology* / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D012038:Regeneration / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism
chemical_list: C575024:ABS-201; D000894:Anti-Inflammatory Agents, Non-Steroidal; D051272:Glucose Transporter Type 1; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D009842:Oligopeptides; C495678:Slc2a1 protein, mouse; D014404:Tubulin; C462941:beta3 tubulin, mouse; C519752:penumbra protein, mouse; D010751:Phosphopyruvate Hydratase
keywords: cell survival; ischemic core; neurotrophic factors; neurovasculature; regeneration