Recombinant Human Granulocyte-colony Stimulating Factor Prevents Cognition Impairment with Chronic Cerebral Ischemia by Promoting Astrocyte Proliferation and Anti-apoptosis in Rats

Recombinant human granulocyte-colony stimulating factor (rhG-CSF), a hemopoietic growth factor naturally generated within the body, has multiple neuroprotective activities. However, the effect of rhG-CSF on astrocyte proliferation and neural apoptosis in rats with chronic cerebral ischemia is unknown. We investigated the effect of rhG-CSF on cognitive function, astrocyte proliferation and neural apoptosis in rats with bilateral common carotid artery ligation (2-vessel occlusion, 2VO). Results from Morris water maze indicated that rhG-CSF treatment shortened the escape latency. For the probe trial, spatial memory was significantly lower for saline-treated 2VO rats than sham-operated and rhG-CSF--treated 2VO rats. Histology revealed the number of pyramidal cells in CA1 region lower in 2VO than sham-operated rats, administration of rhG-CSF prevented the neural loss induced by chronic cerebral ischemia. Immunohistochemistry revealed the expression of glial fibrillary acidic protein (marker of astrocytes) lower in 2VO than in sham-operated rats, rhG-CSF treatment promoted astrocyte proliferation in 2VO rats. Impaired 2VO-induced cognition could be reversed by rhG-CSF treatment, and the neuroprotective effect may be by promoting hippocampal astrocyte proliferation and preventing apoptosis in the CA1 region in rats.