Rat forebrain neurogenesis and striatal neuron replacement after focal stroke
Article first published online: 11 OCT 2002
Copyright © 2002 Wiley-Liss, Inc.
Annals of Neurology
Volume 52, Issue 6, pages 802–813, December 2002
How to Cite
Parent, J. M., Vexler, Z. S., Gong, C., Derugin, N. and Ferriero, D. M. (2002), Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol., 52: 802–813. doi: 10.1002/ana.10393
- Issue published online: 22 NOV 2002
- Article first published online: 11 OCT 2002
- Manuscript Accepted: 23 AUG 2002
- Manuscript Received: 16 APR 2002
- Manuscript Revised: 16 APR 2002
- National Institutes of Health. Grant Numbers: NS42143, NS359502
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.