Morphological and functional changes of blood-brain barrier in kindled rats with cortical dysplasia.
Cortical dysplasia (CD) is one of the major causes contributing to epileptogenesis associated with blood-brain-barrier (BBB) disturbances. The current study investigated the functional and ultrastructural changes of BBB in pentylenetetrazole (PTZ)-kindled rats with CD. Pregnant rats on E17 were exposed to 145 cGy of gamma-irradiation and offspring were used for experiments. The rats were given PTZ three times per week to induce kindling. The permeability of BBB was determined by using sodium fluorescein (NaFlu). Immunohistochemistry for occludin, GFAP and c-fos, western-blot analysis for occludin and electron microscopy for the ultrastructural alterations in BBB were performed. The brain level of NaFlu did not increase in rats with CD and/or kindling. Following administration of a convulsive dose of PTZ, a significant increase in BBB permeability was observed in kindled rats with CD. Occludin immunoreactivity and expression remained essentially unchanged in all groups. Slightly enhanced immunoreactivity for GFAP was observed in all groups except control. c-fos immunoreactivity in brain sections of kindled rats with CD displayed a striking increase by convulsive PTZ challenge. Tight junctions were ultrastructurally intact, whereas markedly increased number of pinocytotic vesicles was noted in brain endothelium of kindled rats with CD by convulsive dose of PTZ. The present study showed that epileptic seizures induced by convulsive PTZ challenge during kindling-mediated epileptogenesis in the presence of CD changed both functional and ultrastructural properties of the BBB and considerably enhanced transendothelial vesicular transport, while paracellular pathway was apparently not involved in this setting.
Kaya
Mehmet
M
Department of Physiology, Istanbul Faculty of Medicine, Turkey. mehkaya@istanbul.edu.tr
Gurses
Candan
C
Kalayci
Rivaze
R
Ekizoglu
Oguzhan
O
Ahishali
Bulent
B
Orhan
Nurcan
N
Oku
Basar
B
Arican
Nadir
N
Ustek
Duran
D
Bilgic
Bilge
B
Elmas
Imdat
I
Kucuk
Mutlu
M
Kemikler
Gonul
G
D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects*; D054220:Malformations of Cortical Development / Q000473:pathology* / Q000503:physiopathology*; D046529:Microscopy, Electron, Transmission; D010433:Pentylenetetrazole / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced; D018709:Statistics, Nonparametric
D005904:Glial Fibrillary Acidic Protein; D016760:Proto-Oncogene Proteins c-fos; D010433:Pentylenetetrazole