Abstracts

Rationale: Leptin (LEP) has been shown to be neuroprotective in vitro against N-methyl-D-aspartate (NMDA)-induced excitotoxicity (Dicou E, Attoub S, Gressens P. Neuroprotective effects of leptin in vivo and in vitro. Neuroreport. 2001 Dec 21;12:3947-51). The NMDA receptor has been implicated in kainic acid (KA)-induced excitotoxicity (Mikati MA. Abi-Habib RJ. El Sabban ME. Dbaibo GS. Kurdi RM. Kobeissi M. Farhat F. Asaad W. Hippocampal programmed cell death after status epilepticus: evidence for NMDA-receptor and ceramide-mediated mechanisms. Epilepsia. 44:282-91,2003). We investigated the effects of LEP against acute cellular damage associated with KA-induced status epilepticus (SE) in adult rats.Methods: Adult Sprague Dawley rats were divided into 3 groups. Group 1 (KA-LEP, n=5) received 12 mg/kg KA intraperitoneally (i.p.), followed by 2 LEP injections i.p., 1 mg/kg each, 1 and 13 hours after KA. Group 2 (KA, n=4) received 12mg/kg KA i.p., then saline instead of LEP. Group 3 (controls, n=3) were sham injected with saline. Rats were sacrificed 24 hours after KA injections, and histological sections at the level of the hippocampus were stained with Toluidine blue for pyramidal neurons surface area measurements and silver stain for optical densities (OD) measurements. Images were analyzed using Metamorph.Results: All rats in the KA and KA-LEP groups underwent behavioral seizures of comparable severity over 16-18 hours. Shrunken degenerating pyramidal neurons were detected on Toluidine blue stain in the CA1 and CA3 hippocampal subfields of the KA group. KA-LEP group and controls had comparable pyramidal cell surface areas in CA1 (70.6 ±3.0 microns for KA-LEP, 72.4 ±1.5 microns for controls, p=0.68), and in CA3 (80.1 ±4.3 microns for KA-LEP, 89.2 ±5.1 microns for controls, p=0.23), and both had significantly larger pyramidal cells than the KA group (54.5 ±3.7 microns for CA1, 53.6 ±4.1 microns for CA3, p<0.05). Compared to the KA group, the KA-LEP group had fewer blackly stained degenerating neurons on silver stain, with 16% lower OD in CA1, and 32% lower OD in CA3.Conclusions: Leptin attenuates acute cellular injury associated with KA-induced SE. Future studies will assess its effectiveness to attenuate the long-term spontaneous recurrent seizures and behavioral changes in this model of temporal lobe epilepsy.