Isolation and characterization of neural stem/progenitor cells from post‐stroke cerebral cortex in mice

Abstract

The CNS has the potential to marshal strong reparative mechanisms, including activation of endogenous neurogenesis, after a brain injury such as stroke. However, the response of neural stem/progenitor cells to stroke is poorly understood. Recently, neural stem/progenitor cells have been identified in the cerebral cortex, as well as previously recognized regions such as the subventricular or subgranular zones of the hippocampus, suggesting that a contribution of cortex-derived neural stem/progenitor cells may repair ischemic lesions of the cerebral cortex. In the present study, using a highly reproducible murine model of cortical infarction, we have found nestin-positive cells in the post-stroke cerebral cortex, but not in the non-ischemic cortex. Cells obtained from the ischemic core of the post-stroke cerebral cortex formed neurosphere-like cell clusters expressing nestin; such cells had the capacity for self-renewal and differentiated into electrophysiologically functional neurons, astrocytes and myelin-producing oligodendrocytes. Nestin-positive cells from the stroke-affected cortex migrated into the peri-infarct area and differentiated into glial cells in vivo. Although we could not detect differentiation of nestin-positive cells into neurons in vivo, our current observations indicate that endogenous neural stem/progenitors with the potential to become neurons can develop within post-stroke cerebral cortex.

ADAM-17/Tumor Necrosis Factor-α-Converting Enzyme Inhibits Neurogenesis and Promotes Gliogenesis from Neural Stem Cells

“…In the discrete lesions induced in the cerebral cortex of adult mice, we observed the appearance of a population of radially oriented nestin-expressing cells, part of which also expressed GFAP, in agreement with previous reports in transient [49] and permanent focal brain ischemia [20] or in stab wound injury [50]. These cells, which may derive from local reactive astrocytes [51] or NG2-expressing glial progenitors [50,52,53], are highly proliferative [49] and have NPC properties [20,51], although they do not generate new neurons in vivo, probably due to local antineurogenic signals.…”

“…These cells, which may derive from local reactive astrocytes [51] or NG2-expressing glial progenitors [50,52,53], are highly proliferative [49] and have NPC properties [20,51], although they do not generate new neurons in vivo, probably due to local antineurogenic signals.…”

Bone Marrow Mononuclear Cells Promote Proliferation of Endogenous Neural Stem Cells Through Vascular Niches After Cerebral Infarction

“…In brief, the left MCA was isolated, electrocauterized, and disconnected just distal to its crossing of the olfactory tract (distal M1 portion) under halothane inhalation. The infarct area in mice of this background has been shown to be highly reproducible and limited to the ipsilateral cerebral cortex [8,15,33,34].…”

“…Permanent focal cerebral ischemia was produced by ligation and disconnection of the distal portion of the left middle cerebral artery (MCA) [8,15,33,34]. In brief, the left MCA was isolated, electrocauterized, and disconnected just distal to its crossing of the olfactory tract (distal M1 portion) under halothane inhalation.…”

“…However, accumulating evidence indicates that NSPCs are present in many parts of the adult brain, including the cortex [8][9][10], subcortical white matter [11], and spinal cord [12][13][14]; that is, outside conventional neurogenic zones, including SVZ and SGZ. Recently, we also found that NSPCs developed in the poststroke area of the cortex in the adult murine brain (ischemia-induced NSPCs) [8], and that ECs promoted the proliferation of these NSPCs, thereby enhancing neurogenesis after ischemia [15]. These observations suggest that augmentation of ECs (e.g., proliferation of ECs [angiogenesis]) can promote neurogenesis by enhancing the proliferation of endogenous ischemia-induced NSPCs.…”