NEUROCHEMISTRYNeuroprotective effects of leptin in vivo and in vitroDicou, EleniCA; Attoub, Samir1; Gressens, PierreAuthor Information INSERM E9935, Hôpital Robert-Debré, 48 Bvd Sérurier, F-75019 Paris; 1INSERM U482, Hôpital Saint-Antoine, Paris, France CACorresponding Author Received 12 September 2001; accepted 15 October 2001 Neuroreport: December 21st, 2001 - Volume 12 - Issue 18 - p 3947-3951 Buy SDC Abstract The present study explored the efficacy of leptin in protecting against in vivo induction of excitotoxic lesions by the glutamatergic analogue ibotenate injected into the developing mouse brain and against in vitro NMDA-induced cell death in primary neuronal cultures. Ibotenate injected intracerebrally (i.c.) to mice on postnatal day 5 produced transcortical necrosis and white matter cysts. Co-treatment with leptin administered i.c. or i.p. reduced ibotenate-induced cortical lesions and white matter cysts by 50%. in vitro, leptin afforded significant neuroprotection of mouse cortical neurons against NMDA cytotoxicity. The neuroprotective effect of leptin was antagonized both in vivo and in vitro by the Jak2 inhibitor AG490, indicating that it was mediated via the leptin receptor and Jak2 activation. These findings are the first evidence for a role of leptin in neuroprotection. © 2001 Lippincott Williams & Wilkins, Inc.