Long-term survival and regeneration of neuronal and vasculature cells inside the core region after ischemic stroke in adult mice

• Type of Material: Article
• Authors: Michael Qize Jiang, Emory University; Ying-Ying Zhao, Emory University; Wenyuan Cao, Emory University; Zheng Zachory Wei, Emory University; Xiaohuan Gu, Emory University; Ling Wei, Emory University; Shan Ping Yu, Emory University
• Language: English
• Date: 2017-07-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 International Society of Neuropathology
• Final Published Version (URL): http://dx.doi.org/10.1111/bpa.12425
• Title of Journal or Parent Work: Brain Pathology
• ISSN: 1015-6305
• Volume: 27
• Issue: 4
• Start Page: 480
• End Page: 498
• Grant/Funding Information: This work was supported by NIH grants NS075338 (LW/SPY), NS062097 (LW), NS091585 (LW), NS073378 (SPY) and VA National Merit grant RX000666 (SPY).; This study was also supported by the O. Wayne Rollins Endowment to SPY.; We acknowledge the Emory Electron Microscope Core supported by NIH S10 grant (S10 RR025679 01).
• Keywords: Neurosciences; TEMPORAL PROFILE; Life Sciences & Biomedicine; Pathology; CORTICAL-NEURONS; regeneration; PHARMACOLOGICALLY INDUCED HYPOTHERMIA; NESTIN EXPRESSION; BLOOD-FLOW; Science & Technology; Neurosciences & Neurology; neurovasculature; FOCAL CEREBRAL-ISCHEMIA; SPONTANEOUS REPERFUSION; Clinical Neurology; TRAUMATIC BRAIN-INJURY; ARTERY OCCLUSION; neurotrophic factors; cell survival; ischemic core; WHISKER-BARREL CORTEX
• Research Categories: Biology, Neuroscience; Health Sciences, Medicine and Surgery

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.