Intracerebral infusion of a second-generation ciliary neurotrophic factor reduces neuronal loss in rat striatum following experimental intracerebral hemorrhage

Abstract

Neuronal and glial cell death in the striatum of a rat model of collagenase-induced intracerebral hemorrhage begins at 1 day and continues for at least 3 weeks. We hypothesized that administration of a neurotrophic agent would reduce neuronal loss in this experimental model. Because it has been shown to protect striatal neurons against excitotoxic injury, a second-generation ciliary neurotrophic factor (CNTF) (AXOKINE) was administered by continuous intracerebral infusion (2 microg/day) beginning 28 h after hemorrhage and continuing for 2 weeks. Magnetic resonance imaging showed that the hematoma size was comparable in control and treated rats prior to treatment. Counts of medium-sized striatal neurons within 320 microm of the hematoma 8 weeks after the hemorrhage revealed a slight but statistically significant benefit with a 42.5% loss in treated rats compared to 51.7% loss in controls. The results suggest that AXOKINE might be protective of striatal neurons in the vicinity of a hemorrhagic lesion.