Gender Difference in the Influence of Antioxidants on the Blood–Brain Barrier Permeability During Pentylenetetrazol-Induced Seizures in Hyperthermic Rat Pups

Abstract

Our purpose in this study was to investigate the protective effects of selenium and vitamin E on the blood-brain barrier (BBB) permeability in rats with convulsion under hyperthermic conditions. To eliminate the effect of sex on BBB, we performed our study on 4- to 5-week-old prepubertal rat pups. Evans-blue was used as a BBB tracer. Convulsions were induced by administration of i.p. pentylenetetrazol. In the selenium group, 4 ppm selenium was added to the drinking water for 4-5 weeks. Vitamin E was administered at 700 mg/kg ip. It was shown that the convulsions, both under normothermic and hyperthermic conditions, caused widespread increase in the BBB permeability (p < 0.05). In addition, a significant difference was observed among female and male rats (f [1, 102] = 6.387, p < 0.05). In convulsions under normothermic conditions, there was a further increase in the BBB permeability (F[3, 102] = 43.534, p < 0.001) and a greater increase of permeability in males compared to females (F[1, 102] = 6.387, p < 0.05). Selenium and vitamin E significantly decreased the BBB destruction caused by convulsions under hyperthermic conditions in males (p < 0.05). Treatment with selenium or vitamin E has beneficial effects on the BBB breakdown during convulsions. But gender differences are very important in BBB permeability under pathological conditions and antioxidant treatments.

Effect of Vitamin E on Blood-Brain Barrier Permeability in Aged Rats with PTZ-Induced Convulsions

“…Vitamin E administered in 300 or 500 mg/kg doses was shown to moderate the intensity of penicillin-sourced epileptiform activity in rats [26]. As was mentioned above, we found that this vitamin demonstrated a protective effect against seizure-related disorders of the BBB permeability in young and adult rats, and the 70 mg/kg dose was effective [12]. At the same time, it is well-known that there are noticeable age-dependent modifications of the epileptic and epileptiform activity [27].…”

“…As was suggested, increased production of ROSs represents one of the crucial factors providing greater BBB permeability values during an after such attacks [12,14]. A protective effect of vitamin E, which is wellknown as an important antioxidant agent, in particular with respect to endothelial cells, was demonstrated in a few studies [12,15].…”

“…Lipid peroxidation in the cerebral endothelial cell membranes is, probably, one of the main reasons for an increment in the BBB permeability [6,7]. The antioxidants, such as vitamins A, C, and (especially) E were shown to exert a protective effect on the BBB during epileptic attacks [12,15,17]. Vitamin E inactivates lipid peroxyl, superoxides, and other reactive species [10,18].…”

“…In our studies, we found that vitamin E exerts a protective effect on the BBB in the course of epileptiform attacks created by introduction of pentylenetetrazole (PTZ) in young and adult rats [12]. However, the effect of vitamin E on the BBB permeability under conditions of convulsions constituted in aged organisms is not clear.…”

Insulin Levels are Decreased in the Cerebrospinal Fluid of Women with Prodomal Alzheimer's Disease

“…BBB dysfunction is indeed a feature of AD [41], and gender differences are important in BBB permeability under pathological conditions [42] but not under normal conditions [43]. In line with this hypothesis, BBB integrity has been shown to be primarily affected in male AD patients [44].…”