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Rat forebrain neurogenesis and striatal neuron replacement after focal stroke
Author(s) -
Parent Jack M.,
Vexler Zinaida S.,
Gong Chao,
Derugin Nikita,
Ferriero Donna M.
Publication year - 2002
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10393
Subject(s) - neurogenesis , neuroblast , subventricular zone , biology , forebrain , neuroscience , doublecortin , rostral migratory stream , striatum , neun , microbiology and biotechnology , neural stem cell , hippocampus , stem cell , central nervous system , dentate gyrus , dopamine , immunohistochemistry , immunology
Abstract The persistence of neurogenesis in the forebrain subventricular zone (SVZ) of adult mammals suggests that the mature brain maintains the potential for neuronal replacement after injury. We examined whether focal ischemic injury in adult rat would increase SVZ neurogenesis and direct migration and neuronal differentiation of endogenous precursors in damaged regions. Focal stroke was induced in adult rats by 90‐minute right middle cerebral artery occlusion (tMCAO). Cell proliferation and neurogenesis were assessed with bromodeoxyuridine (BrdU) labeling and immunostaining for cell type‐specific markers. Brains examined 10–21 days after stroke showed markedly increased SVZ neurogenesis and chains of neuroblasts extending from the SVZ to the peri‐infarct striatum. Many BrdU‐labeled cells persisted in the striatum and cortex adjacent to infarcts, but at 35 days after tMCAO only BrdU‐labeled cells in the neostriatum expressed neuronal markers. Newly generated cells in the injured neostriatum expressed markers of medium spiny neurons, which characterize most neostriatal neurons lost after tMCAO. These findings indicate that focal ischemic injury increases SVZ neurogenesis and directs neuroblast migration to sites of damage. Moreover, neuroblasts in the injured neostriatum appear to differentiate into a region‐appropriate phenotype, which suggests that the mature brain is capable of replacing some neurons lost after ischemic injury.