Neurogenesis After Stroke

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Although it was learned from studies performed on macaque monkeys in the mid-1960s that neurons can be formed within the adult brain (1,2), the dogma until recently has been that brain tissue could not be regenerated in the adult. It is now known that neural stem cells (NSCs) and neural progenitor cells (NPCs) are present in at least two regions in normal adult mammalian brain: the subventricular zone (SVZ) and the subgranular zone (SGZ) in hippocampal dentate gyrus. These cells might promote recovery of neural functions that were lost due to stroke. The proliferation and recruitment of endogenous NSCs and NPCs present after stroke give rise to many, if not all, types of cells found in the adult brain (3-6). The proliferation, migration, and maturation of these cells can be controlled by growth and trophic factors and other signaling molecules, and are affected by ischemia (7,8). Induction of these new neurons, if functional, may provide a novel therapeutic strategy for the treatment of stroke (9 ).

Stroke is characterized by extensive tissue injury in the territory of an affected vessel. The acute stage after onset of stroke is a metabolically, biochemically, and molecularly active time during which a variety of mutagens, trophic factors, adhesion molecules, and intracellular and extracellular matrix molecules, are uniquely elaborated in the stroke brain, particularly in the ischemic boundary zone (the penumbra of infarct) (10-15). This alteration of the ischemic boundary zones occurs at a time at which enhanced neurogenesis in the SVZ and the SGZ can be observed. These two remodeling events may act synergistically to promote repair of brain and recovery of neurologic function. The adult brain, with its endogenous pool of parenchymal cells, has the ability to repair itself; however, the supply of cells is limited, and the survival of the newly formed cells is tenuous within the hostile ischemic environment. Thus, neurogenesis is insufficient to fully restore neurologic function after stroke.

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