Adaptive neurogenesis in the cerebral cortex and contralateral subventricular zone induced by unilateral cortical devascularization: Possible modulation by dopamine neurotransmission.

Abstract

Understanding endogenous neurogenesis and neuronal replacement to mature circuits is a topic of discussion as a therapeutic alternative under acute and chronic neurodegenerative disorders. Adaptive neurogenic response may result as a result of ischemia which could support long-term recovery of behavioral functions. Endogenous sources of neural progenitors may be stimulated by changes in blood flow or neuromodulation. Using a mouse model of unilateral cortical devascularization, we have observed reactive neurogenesis in the perilesional cortex and subventricular zone neurogenic niche. C57BL/6L 4weeks old male mice were craneotomized at 1mm caudal from frontal suture and 1mm lateral from midline to generate a window of 3mm side. Brain injury was produced by removal of the meninges and superficial vasculature of dorsal parietal cortex. BrdU agent (50mg/kg, ip) was injected to lesioned and sham animals, during days 0 and 1 after surgery. Sagittal sections were analyzed at 1, 4, 7, and 10days post-injury. A time-dependent increase in BrdU+ cells in the perilesional parietal cortex was accompanied by augmented BrdU+ cells in the sub ventricular and rostral migratory stream of ipsilateral and contralateral hemispheres. Neural progenitors and neuroblasts proliferated in the lesioned and non-lesioned subventricular zone and rostral migratory stream on day 4 after injury. Augmented contralateral neurogenesis was associated with an increase in vesicular monoamine transporter 2 protein in the striosomal sub ventricular neurogenic niche of non-lesioned hemisphere.