Neuroprotective effects of leptin following kainic acid-induced status epilepticus.
We investigated the potential neuroprotective effects of leptin (LEP) against cellular damage, long-term recurrent spontaneous seizures, and behavioral changes associated with kainate (KA)-induced status epilepticus (SE). Adult Sprague-Dawley rats were sacrificed 24 hours after KA injections, and hippocampi were subjected to histological analysis. In the acute condition, one group received 12 mg/kg KA intraperitoneally (KAac group), and another group received 12 mg/kg KA intraperitoneally, followed by two intraperitoneal LEP injections of 4 mg/kg each, 1 and 13 hours after KA (KALEPac group). For long-term outcomes, one group received KA (KA group), and the other group received three intraperitoneal LEP injections (4 mg/kg at 1 hour, and 2mg/kg at 13 and 24 hours) after KA (KALEP group). Controls were sham manipulated. Behavioral tests started 6 weeks after SE. All rats that received KA underwent behavioral seizures of comparable severity. Compared with the KAac group, the KALEPac group had significantly larger pyramidal cell surface areas and fewer black-stained degenerating neurons with silver stain. The KALEP and KA groups were comparable with respect to recurrent spontaneous seizures, aggression, hyperactivity, and impaired memory. We show that leptin reduces cellular injury associated with KA-induced SE, but does not prevent long-term recurrent spontaneous seizures and behavioral deficits.
Obeid
Makram
M
Department of Pediatrics, Texas Tech University Health Sciences Center, Lubbock, TX, USA. mo2378@mail.cumc.columbia.edu
Frank
Jeffrey
J
Medina
Margarita
M
Finckbone
Velvetlee
V
Bliss
Richard
R
Bista
Binod
B
Majmudar
Shirine
S
Hurst
Daniel
D
Strahlendorf
Howard
H
Strahlendorf
Jean
J
D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D004347:Drug Interactions; D006624:Hippocampus / Q000473:pathology; D007608:Kainic Acid; D020738:Leptin / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced* / Q000473:pathology
D020738:Leptin; D018696:Neuroprotective Agents; D007608:Kainic Acid