Selective Vulnerability to Transcellular Pathway of Blood-Brain Barrier in Chronic Stage of the Kainate Model of Temporal Lobe Epilepsy in Rats

Abstract

Background: The blood-brain barrier (BBB) integrity is severely affected in many epilepsy syndromes including temporal lobe epilepsy (TLE). Aim: In the present study, we investigated the effects of acute and chronic seizures induced by kainic acid (KA) on the transport pathways of BBB in rats. Methods: Electroencephalography (EEG) was recorded to evaluate seizure activity. Immunohistochemistry for claudin-5, a tight junction protein, caveolin-1, and the glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, was performed. Electron microscopy was used to ultrastructurally assess the presence and route of extravasation of horseradish peroxidase (HRP), a permeability marker, in barrier type of brain capillary endothelial cells. Results: The immunoreactivity of claudin-5 and caveolin-1 in hippocampus increased by both acute and chronic seizures (p<0.01), while an increase in GFAP immunoreactivity was found in the hippocampus by only acute seizures (p<0.01). The endothelial cells of brain capillaries in hippocampus and amygdala regions of animals in acute and chronic sham groups showed occasional HRP reaction products. Acute and chronic seizures led to the observation of significantly greater extent of accumulation of HRP reaction products in both brain regions of rats compared to acute and chronic sham groups (p<0.01), while tight junctions were intact in all experimental groups. Conclusion: This study provides immunohistochemical and ultrastructural evidence of BBB disruption through a selective vulnerability of the transcellular transport via an increase in caveolar vesicles in the endothelial cells brain capillaries rather than activation of paracellular pathway in the KA-induced rat model of TLE. Citation: Yilmaz CU, Orhan N, Arican N, Ahishali B, Gürses C, et al. (2018) Selective Vulnerability to Transcellular Pathway of Blood-Brain Barrier in Chronic Stage of the Kainate Model of Temporal Lobe Epilepsy in Rats. Int J Cerebrovasc Dis Stroke : IJCDS-108. DOI: 10.29011/ IJCDS-106. 100008 2 Volume 2018; Issue 01