Methylprednisolone improves the survival of new neurons following transient cerebral ischemia in rats.

Abstract

Cerebral ischemia induced the proliferation and differentiation of neural stem cells in discrete regions of brain. However, only a small fraction of the neural stem/progenitor cells survives. In this report, the effects of methylprednisolone (MP) on proliferation, differentiation and survival of neural progenitor cells were explored through early MP administration after occlusion of the middle cerebral artery (MCAo). Transient cerebral ischemia was induced by middle cerebral artery occlusion in Sprague Dawley male rats. One hour, 1 day, 3 days, 14 days, and 28 days after MCAo, neurological examination was performed to evaluate the neurological deficit. MCAo rats were randomly divided into two groups, MP-group was injected MP (30 mg/kg, i.p.) at 3 h, 12 h, and 24 h after MCAo, and vehicle group was injected equal saline (i.p.). Animals were sacrificed at 3 days, 14 days, and 28 days after MCAo. MP was found to decrease apoptosis and TNF-alpha and IL-6 expression at 3 days after MCAo in the ipsilateral striatum. Moreover, MP significantly increased the migrated new neurons (BrdU+/ DCX+) and immature neurons (BrdU+/Tuj1+) at day 14 after MCAo in the ipsilateral striatum. Likewise, MP increased the number of mature neurons (BrdU+/MAP2+) at 28 days after MCAo. However, MP did not affect the progenitor cell proliferation (BrdU+ and Nestin+) at day 3 after MCAo in the subventricular zone (SVZ), but improved the neurological deficit at day 1 and day 3 after MCAo. These results indicate that early MP administration can improve the neurological deficit and enhance the survival of new neurons in the ipsilateral striatum by inhibiting apoptosis and downregulation of inflammatory response after transient cerebral ischemia in rats.