title: Vagus nerve stimulation inhibits seizure activity and protects blood-brain barrier integrity in kindled rats with cortical dysplasia.
abstract: OBJECTIVE
  This study investigates the effects of vagus nerve stimulation (VNS) on seizure severity and blood-brain barrier (BBB) integrity in kindled rats with cortical dysplasia (CD).
  
  
  METHODS
  Pregnant rats were exposed to 145 cGy of gamma-irradiation on day 17 of pregnancy. In offsprings, kindling was induced by giving subconvulsive doses of pentylenetetrazole. Left VNS was performed for 48 h at output currents of 0.5 or 1 mA. Horseradish peroxidase (HRP) was used to study the BBB permeability. Immunohistochemistry for occludin and P-glycoprotein (P-gp) was also performed.
  
  
  RESULTS
  Kindled rats with CD exhibited seizures with mean Racine's scores of 3.57 ± 1.2 during video EEG recording. Kindled animals with CD receiving VNS at 0.5 and 1.0 mA did not exhibit either clinical or electrophysiological signs of seizure. Immunostaining for occludin, a tight junction protein, in hippocampus remained relatively intact in all groups. VNS-treated and -untreated kindled animals with CD revealed intense immunostaining for P-gp in hippocampal formation (P<0.01). Electron microscopic observations revealed frequent transport vesicles containing electron-dense HRP reaction products in the cytoplasm of brain capillary endothelial cells in both cerebral cortex and hippocampus of kindled animals with CD. Those which were exposed to 1 mA VNS were observed to have brain capillary endothelial cells largely devoid of HRP reaction products in both cerebral cortex and hippocampus.
  
  
  CONCLUSIONS
  The results of this study suggest that VNS therapy at 1 mA inhibits seizure activity and protects BBB integrity by limiting the enhancement of transcellular pathway in kindled animals with CD.
authors: Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors: Mehmet
authors: M
authors: Kaya
authors: Nurcan
authors: N
authors: Orhan
authors: Emrah
authors: E
authors: Karabacak
authors: Metin Berkant
authors: MB
authors: Bahceci
authors: Nadir
authors: N
authors: Arican
authors: Bulent
authors: B
authors: Ahishali
authors: Gonul
authors: G
authors: Kemikler
authors: Atilla
authors: A
authors: Uslu
authors: Aydin
authors: A
authors: Cevik
authors: Canan Ugur
authors: CU
authors: Yilmaz
authors: Mutlu
authors: M
authors: Kucuk
authors: Candan
authors: C
authors: Gürses
mesh_terms: D000016:Abnormalities, Radiation-Induced / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000648:ultrastructure; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D005720:Gamma Rays; D007696:Kindling, Neurologic; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D062793:Occludin / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D055536:Vagus Nerve Stimulation
chemical_list: D062793:Occludin; C568987:Ocln protein, rat