Effects of focal cerebral ischemia on the proliferation, differentiation and migration of intrinsic neural stem cells and progenitor cells

Qionglan YUAN; Chaoxian YANG; Lin GONG; Xiaoqing GAO; Li DENG

ABSTRACT

BACKGROUND:

In the central nervous system(CNS) of normal adults there are neural stem cells or neural progenitor cells, which are capable of self-renewing and multiple differentiating. In normal physiological conditions, intrinsic neural stem cells are in a resting state. What state will they be in during cerebral ischemia?

OBJECTIVE:

To observe the distribution, proliferation and differentiation of intrinsic neural stem cells in focal transient ischemia in rats.

DESIGN:

A randomized controlled exploratory trial based on the rats.

SETTING:

Neurobiological department, histological and embryological department of a medical college.MATERIALS The experiment was conducted in the Neurobiological Department of Luzhou Medical College from July 2001 to July 2002. Altogether 41 healthy adult SD rats of either gender, weighting 250 g - 300 g, were selected.

INTERVENTIONS:

The focal ischemia model was made by blocking middle cerebral artery(MCA) and reperfusing for 0.5 hour, 3 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 5 days and 10 days. Sham-operation group was treated by the same method, but the filament was not long enough to block MCA, and normal rats served as control group. The rats were sacrificed at given time points, and their brains were made into cerebral slices. The single-and double-labeled immunohistochemical staining was employed to detect the proliferation, distribution and differentiation of intrinsic neural stem cells.MAIN OUTCOME

MEASURES:

The distribution, proliferation and differentiation of intrinsic neural stem cells.

RESULTS:

Immunoreactivity of proliferating cell nuclear antigen(PCNA)was present in most ependymal cells in ventricular zone(VZ), and PCNA-positive cells were sparsely distributed in the parenchyma in normal and sham-operation groups. At 3 hours of reperfusion, PCNA-labeled cells were first detected in rostral subventricular zone. At 12 hours of reperfusion and onward, PCNA-positive cells appeared in some choroid plexus cells in bilateral lateral VZ. At day 3 to day 10 of reperfusion, PCNA-labeled cells significantly increased in infarct boundary in preoptic area, striatum and deep layer of frontoparietal cortex. PCNA-labeled cells were first detected in subgranular zone of dentate gyrus 3 days after reperfusion, and increased with time. A very small number of double-positive cells expressed with PCNA and glial fibrillary acidic protein(GFAP) were first detected in infract boundary in preoptic area on day 3 and onward. No double-PCNA and NF-positive cells were detected within 10 days of reperfusion.

CONCLUSION:

Focal cerebral ischemia activates intrinsic neural stem cells, which proliferate and differentiate, and migrate toward ischemic striatum and frontoparietal cortex. This may help clarify the mechanism of functional recovery after ischemia.