Aydın Çevik

Effects of profound hypothermia on the blood-brain barrier permeability in acute and chronically ethanol treated rats.

This study examines the effects of profound hypothermia on the blood-brain barrier (BBB) permeability in ethanol administrated rats. Vascular permeability to intravenously injected Evans blue (EB) was quantitatively examined in the brain regions of rats. Rats were treated with ethanol acute and chronically. Rectal temperature of rats was dropped into 20+/-1 degrees C during profound hypothermia. Mean arterial blood pressure in both acute and chronic ethanol treatments plus hypothermia significantly dropped into low levels as well as in hypothermia alone (P<0.01). Hypothermia led to a significant increase in the content of EB dye in the brain regions of rats (P<0.05). Both acute and chronic ethanol treatments plus hypothermia did not lead to a significant increase in the BBB permeability against intravenously injected EB dye. We conclude that ethanol intake protects the BBB against the effects of hypothermia.

Effect of Blueberry Feeding on Lipids and Oxidative Stress in the Serum, Liver and Aorta of Guinea Pigs Fed on a High-Cholesterol Diet

We investigated the effect of blueberries (BB) on lipids and oxidative stress parameters in hypercholesterolemic guinea pigs. The animals were fed for 75 d on a high-cholesterol (HC) diet supplemented with fresh BB. BB reduced oxidative stress and cholesterol accumulation in the aorta and liver of the guinea pigs. This effect may be related to its antioxidative potential and lipid-reducing effect.

Topiramate reduces blood―brain barrier disruption and inhibits seizure activity in hyperthermia-induced seizures in rats with cortical dysplasia

We investigated the effects of topiramate (TPM), a novel broad spectrum anticonvulsant, on seizure severity, survival rate and blood-brain barrier (BBB) integrity during hyperthermic seizures in rats with cortical dysplasia (CD). Offsprings of irradiated mothers were used in this study. To show the functional and morphological alterations in BBB integrity, quantitative analysis of Evans blue (EB) extravasation, immunohistochemistry and electron microscopic assessment of horseradish peroxidase (HRP) permeability were performed. Rats with CD exposed to hyperthermia exhibited seizures with mean Racines scores of 3.92 ± 1.2. Among the rats with CD pretreated with TPM, 21 of 24 rats showed no sign of seizure activity upon exposure to hyperthermia (p<0.01). The immunoreactivity of occludin, a tight junction protein, remained essentially unaltered in capillaries of hippocampus in all groups. In animals with CD exposed to hyperthermia, the significantly increased p-glycoprotein immunoreactivity in hippocampus (p<0.01) was slightly decreased by TPM pretreatment. Hyperthermic seizures increased BBB permeability to EB in animals with CD, but TPM pretreatment decreased the penetration of the tracer into the brain in these animals (p<0.01). Ultrastructurally frequent vesicles containing HRP reaction products were observed in capillary endothelial cells in cerebral cortex and hippocampus of rats with CD subjected to hyperthermia-induced seizures, and TPM pretreatment prevented the development of HRP reaction products in these animals. The results of this study suggest that TPM inhibits seizure activity and maintains BBB integrity in the course of febrile seizures in the setting of CD.

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

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 Racines 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.

Effect of aluminum on the blood-brain barrier permeability in acute and chronically hyperglycemic rats.

This study examined the changes in blood-brain barrier (BBB) permeability following acute aluminum (Al) exposure during acute and chronic hyperglycemia in rats. Acute hyperglycemia was induced by intraperitoneal injection of glucose solution at 30 min after giving Al. Chronic hyperglycemia was made by an injection of alloxan monohydrate. BBB permeability was measured in the four regions of the brain at 1 h after administrating Al by spectrophotometric quantification of Evans blue (EB) dye. The extravasation of EB dye was significantly more extensive in the two regions of brain in the groups treated with Al, Al plus glucose, and alloxan plus Al than in the groups treated with saline, glucose, and alloxan alone (p<0.05). Under acute and chronic hyperglycemia plus Al treatment, the BBB permeability to EB was significantly higher than that observed solely in Al-treated rats (p<0.05). These data indicate that Al toxicity leads to an additional increase in BBB permeability, in which acute and chronic hyperglycemia potentiates the effects of Al to enhance BBB permeability to EB.