FLUNARIZINE ENHANCES RAT RETINAL GANGLION-CELL SURVIVAL AFTER AXOTOMY

Abstract

After axotomy most central nervous neurons including retinal ganglion cells (RGCs) die in a few weeks, although their somata are not injured. This neuronal death could be due to lack of retrogradely transported target derived neurotrophic factors or due to a calcium overload after excessive release of excitatory amino acids from dying cells. Flunarizine, as a potent blocker of voltage dependent Ca2+ channels and in higher concentration being an inhibitor of the Ca2+/Calmodulin-dependent protein kinase II, is able to mimick the neurotrophic effect of NGF on dorsal root ganglion (DRG) neurons. To examine its neuroprotective value in the central nervous system (CNS), flunarizine (5 mg/kg body weight) was given daily to rats after unilateral axotomy of the optic nerve. The density of retrogradely labelled retinal ganglion cells (RGCs) was determined 14 days after axotomy. It could be demonstrated that flunarizine significantly enhanced RGC survival after axotomy in adult rats (P < 0.001; 1065 +/- 142 vs. 922 +/- 237 RGCs/mm2).