Morphological and functional changes of blood–brain barrier in kindled rats with cortical dysplasia

• Published in: Brain research Vol. 1208; pp. 181 - 191
• Main Authors: Kaya, Mehmet, Gurses, Candan, Kalayci, Rivaze, Ekizoglu, Oguzhan, Ahishali, Bulent, Orhan, Nurcan, Oku, Basar, Arican, Nadir, Ustek, Duran, Bilgic, Bilge, Elmas, Imdat, Kucuk, Mutlu, Kemikler, Gonul
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 07-05-2008; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Biological and medical sciences; Blood-Brain Barrier - pathology; Blood-Brain Barrier - physiopathology; Blood-Brain Barrier - ultrastructure; Blood–brain barrier; c-fos; Capillary Permeability - drug effects; Capillary Permeability - physiology; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cortical dysplasia; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; GFAP; Glial Fibrillary Acidic Protein - metabolism; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Kindling; Kindling, Neurologic - drug effects; Malformations of Cortical Development - pathology; Malformations of Cortical Development - physiopathology; Medical sciences; Microscopy, Electron, Transmission; Nervous system (semeiology, syndromes); Neurology; Occludin; Pentylenetetrazole - pharmacology; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; Seizures; Seizures - chemically induced; Sodium fluorescein; Statistics, Nonparametric; Vertebrates: nervous system and sense organs; Cortical dysplasia; Kindling; c-fos; Blood–brain barrier; Seizures; Sodium fluorescein; Occludin; GFAP; Nervous system diseases; Dysplasia; Rat; Epilepsy; Rodentia; Central nervous system; Blood brain barrier; Cerebral disorder; Encephalon; Vertebrata; Blood-brain barrier;Cortical dysplasia;Kindling;Seizures;Sodium fluorescein;Occludin;c-fos;GFAP; Mammalia; Animal; Central nervous system disease; Morphological change
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.02.101

Abstract 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.