Vagus nerve stimulation inhibits seizure activity and protects blood-brain barrier integrity in kindled rats with cortical dysplasia.

Abstract

AIMS:

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).

MAIN 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.

KEY FINDINGS:

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.

SIGNIFICANCE:

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: Mehmet Kaya, Nurcan Orhan, Emrah Karabacak, Metin Berkant Bahceci, Nadir Arican, Bulent Ahishali, Gonul Kemikler, Atilla Uslu, Aydin Cevik, Canan Ugur Yilmaz, Mutlu Kucuk, Candan Gürses
• Journal: Life sciences (Life Sci) Vol. 92 Issue 4-5 Pg. 289-97 (Mar 12 2013) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 23333826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Occludin
• Ocln protein, rat

Topics

• Abnormalities, Radiation-Induced (etiology, metabolism, pathology)
• Animals
• Blood-Brain Barrier (metabolism, ultrastructure)
• Capillaries (metabolism, pathology)
• Disease Models, Animal
• Electroencephalography
• Endothelium, Vascular (metabolism, pathology)
• Female
• Gamma Rays
• Kindling, Neurologic
• Male
• Malformations of Cortical Development (complications, metabolism, pathology)
• Occludin (metabolism)
• Pregnancy
• Prenatal Exposure Delayed Effects (etiology, metabolism, pathology)
• Rats
• Rats, Wistar
• Seizures (etiology, metabolism, pathology, prevention & control)
• Vagus Nerve Stimulation