Gestational treatment of folic acid attenuates blood-brain barrier leakage in pregnant- and prepubertal rats after pentylenetetrazole-induced seizure.

OBJECTIVES: Folic acid (FA) is physiologically important in mammals and is a common vitamin supplement used during pregnancy and lactation. Numerous studies have reported that FA significantly improves endothelial function. The blood-brain barrier (BBB) plays an important role in maintaining the microenvironment required for neuronal function, but its unique structure is damaged by epileptic seizures. The aim of this study was to evaluate the potential protective role of FA on BBB leakage, as well as on the reactive astrogliosis in pregnant rats and their prepubertal offspring during pentylenetetrazole (PTZ)-induced epileptic seizure. METHODS: Pregnant rats were treated with FA (5 mg/kg) and PTZ on gestational days 0-19 and 19, respectively. The pups were treated with PTZ at puberty. Evans blue was used to evaluate BBB integrity. Reactive astrogliosis was defined using immunohistochemical analysis for glial fibrillary acidic protein (GFAP). Mean arterial blood pressure (MABP) was measured at the femoral artery. RESULTS: A moderate decrease in BBB leakage was observed in FA-treated pregnant and prepubertal animals (P < 0.05). MABP was decreased significantly in pregnant rats (P < 0.05). The epilepsy-induced increase in MABP was less prominent in pregnant animals (P < 0.05). GFAP intensity decreased in PTZ-treated pregnant animals (P < 0.01) and FA-treated prepubertal rats. DISCUSSION: Our findings suggest that FA, which is used as a maternal vitamin to promote normal fetus development, may be beneficial against seizure-induced neuronal damage by decreasing BBB leakage and reactive astrogliosis in pregnant and prepubertal rats.

Type 1 diabetes exacerbates blood-brain barrier alterations during experimental epileptic seizures in an animal model.

The aim of this study was to perform the effects of diabetes on the permeability of the blood-brain barrier (BBB) during pentylenetetrazole (PTZ)-induced epileptic attacks. For this propose, the animals were divided into four groups. These groups contained were intact, PTZ-treated, diabetic and PTZ-treated diabetic individuals, respectively. To evaluate the functioning of the BBB, Evans blue was used as a BBB permeability indicator, and the expressions of zonula occludens-1 and glial fibrillary acidic protein involving the functioning of the BBB were determined immunohistochemically. Also, the changes in the release of serum tumour necrosis factor-alpha and interleukin-10 and interleukin-12 were studied by using enzyme-linked immunosorbent assay method. BBB permeability in the seizures under diabetic conditions showed a considerable increase (p < 0·01) in all of the brain we studied. The immunoreactive staining intensity of zonula occludens-1 and glial fibrillary acidic protein was found reduced in the brain regions of diabetic rats (p < 0·01). However, the serum level of tumour necrosis factor-alpha increased in diabetes and diabetes + PTZ groups, and the serum level of interleukin-12 increased significantly in all experimental groups (p < 0·05). In conclusion, diabetes dramatically increases BBB damage during epileptic seizures, and it may be derived from an elevation of paracellular passage.

The effects of zinc treatment on the blood-brain barrier permeability and brain element levels during convulsions.

We evaluated the effect of zinc treatment on the blood-brain barrier (BBB) permeability and the levels of zinc (Zn), natrium (Na), magnesium (Mg), and copper (Cu) in the brain tissue during epileptic seizures. The Wistar albino rats were divided into four groups, each as follows: (1) control group, (2) pentylenetetrazole (PTZ) group: rats treated with PTZ to induce seizures, (3) Zn group: rats treated with ZnCl(2) added to drinking water for 2 months, and (4) Zn + PTZ group. The brains were divided into left, right hemispheres, and cerebellum + brain stem regions. Evans blue was used as BBB tracer. Element concentrations were analyzed by inductively coupled plasma optical emission spectroscopy. The BBB permeability has been found to be increased in all experimental groups (p < 0.05). Zn concentrations in all brain regions in Zn-supplemented groups (p < 0.05) showed an increase. BBB permeability and Zn level in cerebellum + brain stem region were significantly high compared to cerebral hemispheres (p < 0.05). In all experimental groups, Cu concentration decreased, whereas Na concentrations showed an increase (p < 0.05). Mg content in all the brain regions decreased in the Zn group and Zn + PTZ groups compared to other groups (p < 0.001). We also found that all elements' levels showed hemispheric differences in all groups. During convulsions, Zn treatment did not show any protective effect on BBB permeability. Chronic Zn treatment decreased Mg and Cu concentration and increased Na levels in the brain tissue. Our results indicated that Zn treatment showed proconvulsant activity and increased BBB permeability, possibly changing prooxidant/antioxidant balance and neuronal excitability during seizures.

The effects of hypoglycemic and alcoholic coma on the blood-brain barrier permeability.

In this investigation, the effects of hypoglycemic coma and alcoholic coma on the blood-brain barrier (BBB) permeability have been compared. Female adult Wistar albino rats weighing 180-230 g were divided into three groups: Control group (n=8), Alcoholic Coma Group (n=18), and Hypoglycemic Coma group (n=12). The animals went into coma approximately 3-4 hours after insulin administration and 3-5 minutes after alcohol administration. Evans blue (4mL/kg) was injected intravenously as BBB tracer. It was observed that the alcoholic coma did not significantly increase the BBB permeability in any of the brain regions when compared to control group. Changes in BBB permeability were significantly increased by the hypoglycemic coma in comparison to the control group values (p<0.01). Our findings suggest that hypoglycemic and alcoholic coma have different effects on the BBB permeability depending on the energy metabolism.

Lifelong consumption of sodium selenite: gender differences on blood-brain barrier permeability in convulsive, hypoglycemic rats.

The aim of this study was to compare the effects of hypoglycemia and induced convulsions on the blood-brain barrier permeability in rats with or without lifelong administration of sodium selenite. There is a significant decrease of the blood-brain barrier permeability in three brain regions of convulsive, hypoglycemic male rats treated with sodium selenite when compared to sex-matched untreated rats (p<0.05), but the decrease was not significant in female rats (p>0.05). The blood-brain barrier permeability of the left and right hemispheres of untreated, moderately hypoglycemic convulsive rats of both genders was better than their untreated counterparts (p<0.05). Our results suggest that moderate hypoglycemia and lifelong treatment with sodium selenite have a protective effect against blood-brain barrier permeability during convulsions and that the effects of sodium selenite are gender-dependent.

Gender difference in the influence of antioxidants on the blood-brain barrier permeability during pentylenetetrazol-induced seizures in hyperthermic rat pups.

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.

Influence of 50 Hz frequency sinusoidal magnetic field on the blood-brain barrier permeability of diabetic rats.

The combined effects of diabetes and a 50 Hz, 5 mT RMS flux density sinusoidal magnetic field for 8 h a day, for 21 consecutive days on the permeation of Evans-blue dye through the blood-brain barrier were studied in male Wistar albino rats. Our results suggest that magnetic field has no effect on the blood-brain barrier permeability in normoglycemic animals, but that diabetic rats are vulnerable to magnetic fields.

Influence of surgical pain stress on the blood-brain barrier permeability in rats.

Effect of surgical pain stress on the blood-brain barrier permeability was investigated in rats. The animals were divided into four groups: Group 1: control, Group 2: immobilization stress, Group 3: acute hypertension, Group 4: immobilization stress + surgical pain stress. Bilateral hid paw surgical wounds for cannulations were applied in animals' inguinal regions under diethyl-ether anesthesia, then the animals were awaken from anesthesia to produce surgical pain stress. Evans-blue was used as a blood-brain barrier tracer. There is no significantly blood-brain barrier breakdown after short-time immobilization stress, but after adrenalin hypertension blood-brain barrier permeability was increased especially on frontal and occipital cortices in 50% of the animals. Surgical pain stress increased blood-brain barrier permeabiliy in comparison to acute adrenalin-induced hypertension (p < 0.01). In surgical pain stress-induced animals distinct Evans-blue leakage was observed in the occipital, frontal and parieto-temporal cortices.

Influence of hypoosmolality on the blood-brain barrier permeability during epileptic seizures.

Changes in the blood-brain barrier permeability to macromolecules were investigated during pentylenetetrazol-induced seizures, using Evans-blue as an indicator, in water-intoxicated and nonintoxicated Wistar albino (210-250 g) adult rats of both sexes. Evans-blue albumin extravasation was judged visually and estimated quantitatively with a spectrophotometer using homogenized brain to release the dye. Hypoosmolar treatment (water intoxication) was performed by the intraperitoneal administration of distilled water to a volume of 10% of the body weight; Six groups of rats were studied. Group I: female control (n=10), Group II: male control (n=10), Group III: nonwater-intoxicated female+seizure (n=15), Group IV: nonwater-intoxicated male+seizure (n=15), Group V: water-intoxicated female+seizure (n=15), Group VI: water-intoxicated male+seizure (n=15). Approximately 2 h after the injection of water, the plasma osmolarity had decreased by 25-30 mosm. Our results revealed that in female rats, the extravasation of Evans-blue albumin was greater in the brains of water-intoxicated rats compared to nonwater-intoxicated rats after pentylenetetrazol-induced seizures. In addition, hypoosmotic female rats were shown to have a larger increase in blood-brain barrier permeability than hypoosmotic male rats after pentylenetetrazol-induced seizures. This difference between male and female rats was found to be significant (P=.005).

Comparison of the activities of Na(+),K(+)-ATPase in brains of rats at different ages.

BACKGROUND: Na(+),K(+)-ATPase is known to be responsible for the ionic homeostasis in excitable tissues. The energy cost of Na(+),K(+)-ATPase activity is increased in the active brain, so it would be important to ascertain whether defects in brain metabolism in aging are associated with changes in the properties of Na(+),K(+)-ATPase. OBJECTIVE: The aim of this study was to investigate the influence of age on the Na(+),K(+)-ATPase activity in developing rat brains from the age of 1 day to 24-28 months. METHODS: Crude microsomal preparations were obtained from the brains of newborn (n = 8), 18-day-old (n = 8), 4- to 5-month-old (n = 12), and 24- to 28-month-old (n = 14) rats. Then the ATPase activity was measured and expressed as micromoles of inorganic phosphorus released per milligram of protein per hour. RESULTS: The increased tendency in brain Na(+),K(+)-ATPase activity from newborn to 18 days of age suggested that the Na pump is mature soon after birth. No significant differences could be detected in the enzyme activity between newborn and adult rats. In contrast, the Na(+),K(+)-ATPase activity in aged rat brains was found to be significantly lower than in the other age groups of rats tested (p < 0.001). CONCLUSION: Our results suggest that aging-induced inhibitions in the brain Na(+),K(+)-ATPase activity may be implicated in the depression of neuronal excitability and in the age-related impairments of cognitive functions.