Abstracts

It is well known that vitamin D is neuroprotective in stroke and 6-OHDA toxicity by GDNF induction and inhibits induction of iNOS by activation of microglia in experimental encephalomyelitis. Our hypothesis is that vitamin D may be neuroprotective by inhibiting activation of microglia. To evaluate the effect of vitamin D on the neuronal injury, we used lithium-pilocarpine induced status epilepticus model.
Vitamin D (1a,25-Dihydroxyvitamin D[sub]3[/sub];1 [mu] g/kg IP) or vehicle (ethanol, 2.4 [mu] l/ml/kg IP) was administered every 24 h for 7 days before pilocarpine injection. Lithium (3 mEq/kg) was pretreated 24 h before pilocarpine injection (40 mg/kg). After injection, the behavior of animals was observed and the survived animals were sacrificed 72 h after status epilepticus for histological examination and immunohistochemistry.
All animals including vitamin D (N=12) and vehicle (N=12) treated groups showed status epilepticus. Vitamin D treated group had a higher survival rate (vitamin D 83% vs vehicle 50% at 72 h after status epilepticus, P[lt]0.01). Cresyl violet staining demonstrated hippocampal neuronal damage in CA1, CA3, hilus, and dentate gyrus in animals pretreated with vehicle (N=6), but significantly decreased neuronal damage in animals pretreated with vitamin D (N=10) (Mann-Whitney U-test, P[lt]0.05). Immunohistochemistry by isolectin B4 revealed increased microglia in CA1, CA3, hilus, and dentate gyrus in vehicle treated group, but significantly decreased microglia in vitamin D treated group (Mann-Whitney U-test, P[lt]0.05).
These results indicate that vitamin D inhibits microglia activation and that vitamin D protects hippocampal neurons from damages induced by lithium-pilocarpine seizures. This neuroprotective effect of vitamin D may be mediated by inhibiting activation of microglia. Better mechanistic understanding of vitamin D[rsquo]s effect in neuroprotection could provide novel approaches for more effective therapy in epilepsy to protect from seizure induced neuronal injury.