Neural stem cells (NSCs) in the adult rat subventricular zone (SVZ) generate new striatal neurons during several months after ischemic stroke. Whether the microglial response associated with ischemic injury extends into SVZ and influences neuroblast production is unknown. Here, we demonstrate increased numbers of activated microglia in ipsilateral SVZ concomitant with neuroblast migration into the striatum at 2, 6, and 16 weeks, with maximum at 6 weeks, following 2 h middle cerebral artery occlusion in rats. In the peri-infarct striatum, numbers of activated microglia peaked already at 2 weeks and declined thereafter. Microglia in SVZ were resident or originated from bone marrow, with maximum proliferation during the first 2 weeks postinsult. In SVZ, microglia exhibited ramified or intermediate morphology, signifying a downregulated inflammatory profile, whereas amoeboid or round phagocytic microglia were frequent in the peri-infarct striatum. Numbers of microglia expressing markers of antigen-presenting cells (MHC-II, CD86) increased in SVZ but very few lymphocytes were detected. Using quantitative PCR, strong short- and long-term increase (at 1 and 6 weeks postinfarct) of insulin-like growth factor-1 (IGF-1) gene expression was detected in SVZ tissue. Elevated numbers of IGF-1-expressing microglia were found in SVZ at 2, 6, and 16 weeks after stroke. At 16 weeks, 5% of microglia but no other cells in SVZ expressed the IGF-1 protein, which mitigates apoptosis and promotes proliferation and differentiation of NSCs. The long-term accumulation of microglia with proneurogenic phenotype in the SVZ implies a supportive role of these cells for the continuous neurogenesis after stroke.

Background and Purpose-Stroke induced by middle cerebral artery occlusion (MCAO) triggers increased neurogenesis in the damaged striatum and nondamaged hippocampus of young adult rodents. We explored whether stroke influences neurogenesis similarly in the aged brain. Methods-Young adult (3 months) and old (15 months) rats were subjected to 1 hour of MCAO, and new cells were labeled by intraperitoneal injection of 5-bromo-2Ј-deoxyuridine 5Ј-monophosphate (BrdU), a marker for dividing cells, for 2 weeks thereafter. Animals were euthanized at 7 weeks after the insult, and neurogenesis was assessed immunocytochemically with antibodies against BrdU and neuronal markers with epifluorescence or confocal microscopy. Results-Young and old rats exhibited the same increased numbers of new striatal neurons after stroke, despite basal cell proliferation in the subventricular zone being reduced in the aged brain. In contrast, both the number of stroke-generated granule cells and basal neurogenesis in the dentate subgranular zone were lower in old compared with young animals. Also, the ability of newly formed cells to differentiate into neurons was impaired in the aged dentate gyrus. Conclusions-Basal neurogenesis is impaired in the subgranular and subventricular zones of aged animals, but both regions react to stroke with increased formation of new neurons. The magnitude of striatal neurogenesis after stroke is similar in young and old animals, indicating that this potential mechanism for self-repair also operates in the aged brain. Key Words: cerebral arteries Ⅲ hippocampus Ⅲ ischemia Ⅲ neuronal plasticity Ⅲ stem cells Ⅲ stroke, ischemic T he production of neurons in the mammalian brain continues throughout life. Neurons generated in the subventricular zone (SVZ) migrate to the olfactory bulb, and they differentiate into interneurons. Neurogenesis in the dentate subgranular zone (SGZ) gives rise to neurons in the granule cell layer (GCL). Basal hippocampal and olfactory bulb neurogenesis declines in aged animals, 1-4 but different treatments also increase the production of new neurons in old brains. 1,5,6 Stroke induced by middle cerebral artery occlusion (MCAO) in young adult rodents triggers increased neurogenesis in the SGZ/GCL and SVZ. [7][8][9][10][11] This insult causes neuronal loss in the striatum and cerebral cortex, whereas hippocampal formation is spared. The SVZ neuroblasts migrate into the damaged striatal area and adopt the phenotype of projection neurons. 8 -10 Stroke leads to deficits in hippocampus-associated spatial memory, 12 and the increase in SGZ neurogenesis might aim to counteract cognitive impairments. Striatal neurogenesis, therefore, may contribute to recovery of stroke-impaired motor function.Ischemic stroke occurs more often in aged humans. It is therefore of major clinical interest to explore whether the aged brain retains the capacity for stroke-induced neurogenesis. Here we show that both basal and stroke-induced hippocampal neurogenesis is attenuated in old animals. In contrast, despite redu...

No abstract

No abstract