Inflammation in rat pups subjected to short hyperthermic seizures enhances brain long-term excitability.
Inflammatory processes in response to infection are involved in the pathophysiological mechanisms of febrile seizures (FS). Prolonged FS may promote the development of temporal lobe epilepsy. It has been shown in rats that prolonged hyperthermic seizures (HS) are followed by long-term modification of brain excitability. To examine whether short FS results in modification of brain excitability, we induced an inflammatory response in combination with short HS.


METHODS
HS were induced in rat pups at either P11 or P16 using a heating lamp with a continuous monitoring of the core temperature. Rat pups were maintained at the temperature seizure threshold during 5 min. In order to induce an inflammatory response, lipopolysaccharide (LPS, Eschericha coli 055:B5) was injected i.p. at 5 microg/kg or 50 microg/kg, 2h prior seizure induction. After 1 month, pentylenetetrazol threshold (PTZth) was used to assess the change of brain excitability. Histological studies were performed 24h after the FS (Fluorojade-B) and after the PTZth (cresyl violet).


RESULTS
The temperature thresholds to induce the seizures were not different among the groups. The PTZth was not significantly different between sham and FS only groups, and decreased dose-dependently when LPS was combined to FS. Histological studies suggested the absence of cell injury.


CONCLUSIONS
Lower PTZth obtained by using LPS in combination with HS in rat pups suggests a change in brain excitability. Our model with only 5 min of HS in combination with LPS suggests that an inflammatory response could, in part, explain long-term change in brain excitability following short FS.
Auvin
Stéphane
S
Pediatric Neurology Department, Robert Debré Children Hospital, APHP, Paris, France. auvin@invivo.edu
Porta
Natacha
N
Nehlig
Astrid
A
Lecointe
Cécile
C
Vallée
Louis
L
Bordet
Régis
R
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature; D002452:Cell Count; D005334:Fever / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D003294:Seizures, Febrile / Q000473:pathology*; D013194:Staining and Labeling
D008070:Lipopolysaccharides