Abstracts

Rationale: The blood brain barrier (BBB) is an intricate and highly selective permeable barrier formed by endothelial cells of brain capillaries, and serves to protect the neuronal microenvironment and regulate brain homeostasis under physiological conditions. It is controversial whether febrile seizures (FS) alter the permeability of the BBB. Clear alterations in BBB permeability has been reported in juvenile rats in several experimental models FS (EFS). However, this has not been shown in ten days old (P10) rats, which is the peak age of susceptibility to EFS in rodents. The mechanism by which EFS may alter BBB permeability is unknown. The transient receptor potential vanilloid type 1 (TRPV1) channel has been reported to alter BBB permeability in juvenile rats. This has important implications given they are activated at approximately 42 °C which is the threshold temperature of EFS. We hypothesized that EFS would increase BBB permeability in P10 rats through activation of TRPV1 channels. Methods: BBB integrity was determined by quantifying the extravasation of albumin in brain tissue of P10 rat pups. Pups were either treated with the TRPV1 agonist piperine (PIP, n=6) or the antagonist capsazepine (CPZ, n=4) at a dose of 300 mg/kg administered intraperitoneally 30 minutes prior to the induction of EFS. Half the pups for each group were then placed in a Plexiglas box and exposed to a stream of warm dry air (45-50^oC) until a generalized convulsion occurred. Results were compared with controls with (n=3) or without (n=3) EFS. All rats were then transcardially perfused and the brains harvested and cut into 50 µm sections. Immunohistochemical techniques were used to stain for albumin, and comparable brain sections analyzed. Parenchymal albumin extravasates were counted in 4 brain sections per rat and compared between treatment groups. Results: There was no differences in the number of extravasates counted between rat pups exposed to EFS (0.194/mm² +/- 0.088) and naïve (0.189/mm² +/- 0.057) animals. PIP treatment did not significantly alter the number of albumin extravasates (0.0988/mm² +/- 0.038) as compared to the EFS and naïve groups. CPZ treatment significantly increased the number of albumin extravasates (0.6026/mm² +/- 0.1316) as compared to PIP + EFS (0.0956/mm² +/- 0.057), PIP, EFS and naïve contral animals (p<0.001). There were no significant differences in the number extravasates between the EFS + CPZ (0.7140/mm