[Show abstract][Hide abstract] ABSTRACT: 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.
Biological trace element research 11/2012; · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Bosnian journal of basic medical sciences / Udruzenje basicnih mediciniskih znanosti = Association of Basic Medical Sciences 05/2011; 11(2):108-12. · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effect of vitamin E on blood-brain barrier (BBB) permeability was studied under conditions of pentylenetetrazole (PTZ)-induced
convulsions in aged (23- to 24-month-old) male albino rats; Evans Blue was used as a tracer. The BBB permeability was found
to increase considerably in rats with PTZ-evoked seizures; the Evans Blue contents in the left and right hemispheres and cerebellum
+ brainstem region were significantly higher than those in the control. Vitamin E at a dose of 70 mg/kg exerted practically
no beneficial effect on the increased BBB permeability in rats with seizures, while a greater dose of vitamin E (700 mg/kg)
exerted a significant protective effect, especially with respect to the cerebellum + brainstem regions (P < 0.01). The seizure-related rise in the arterial blood pressure was also smaller in the latter experimental group. Thus,
our observations confirm the importance of the vitamin E dose as a protective factor for BBB permeability and demonstrate
that the dose dependence of this antioxidant in aged animals differs from that in younger organisms.
Keywordsepilepsy–seizures–blood-brain barrier–permeability–pentylenetetrazole–vitamin E–geriatric
[Show abstract][Hide abstract] ABSTRACT: 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.
Biological Trace Element Research 07/2008; 124(1):12-9. · 1.31 Impact Factor
[Show abstract][Hide abstract] 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.
Biological Trace Element Research 07/2007; 118(1):77-83. · 1.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
Life Sciences 03/2004; 74(16):1973-9. · 2.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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).
Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2003; 27(4):701-4. · 3.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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).
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.
[Show abstract][Hide abstract] ABSTRACT: Pentylenetetrazol-induced seizures in rats lead to the breakdown of the blood-brain barrier. We compared the disruption of the blood-brain barrier during epileptic seizure in untreated rats and in rats treated with vitamin E or selenium. The rats were supplemented with nontoxic doses of sodium selenite (4 pp) in drinking water for 3 months, or vitamin E (70 mg/kg) was given intraperitoneally for 30 min before the pentylenetetrazole injection. Evans-blue was used as a blood-brain barrier tracer and was given intravenously at a dose of 4 ml/kg of a 2% solution. The rats were divided into four experimental groups. Group I: control (n = 24); Group II: pentylenetetrazole-induced seizure (n = 12); Group III: vitamin E injected + seizure (n = 12); Group IV: Selenium supplemented + seizure (n = 12). The rats subjected to epileptic seizures showed Evans-blue albumin extravasations especially in the thalamic nuclei, brainstem, occipital, and frontal cortex. Mean values for Evans-blue dye were found to be 0.28 +/- 0.04 mg % brain tissue in control rats and 1.6 +/- 0.2 mg % brain tissue after epileptic seizures (P < 0.01). The magnitude of distribution of the blood-brain barrier during epileptic seizures was significantly less in rats treated with vitamin E or selenium. The mean value for Evans-blue dye was found to be 1.2 +/- 0.1 mg % brain tissue in selenium supplemented rats and 1.2 +/- 0.1 mg % brain tissue in vitamin E injected rats after epileptic seizures. This difference between treated and untreated animals was found to be significant (P < 0.05). The findings of the present study suggest that free radicals contribute to disruption of the blood-brain barrier during pentylenetetrazol-induced seizures.
Journal of Neuroscience Research 12/2001; 66(4):674-8. · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The interrelationship between the breakdown of the blood-brain barrier according to the Evans-blue passage and an abrupt increase in blood pressure (DeltaP) was studied in rats subjected to adrenaline-induced acute hypertension and also pentylenetetrazol-induced seizures. Arterial blood pressure was increased by adrenaline, then immediately i.v. nifedipine was injected and subsequently decreased to the control value in the acute hypertensive group. Arterial blood pressure was increased by pentylenetetrazol, then immediately GABA (gamma-aminobutiric acid) was injected and the blood pressure was decreased to the control value in the seizure group. The animals were divided into five groups. Group I: control; Group II: acute hypertension; Group III: acute hypertension + nifedipine; Group IV: seizure; Group V: seizure + GABA. The Evans-blue dye content was found to be 0.25 +/- 0.01 mg% in the whole brain in the control animals, and 0.803 +/- 0.1 mg% in the acute hypertensive group. This difference between these groups was found to be significant: P< 0.01. In the nifedipine group (Group III) the Evans-blue content was 0.30 +/- 0.1 mg% in the whole brain; and there was no significant difference between control values and nifedipine-treated animals (P> 0.5). The Evans-blue content was 1.6 +/- 0.2 mg% in the whole brain during seizure, and decreased to 0.36 +/- 0.1 mg% after GABA injection was administered. There was also no significant difference between the control value and the GABA-treated animals (P> 0.5). These results have shown that an abrupt increase in blood pressure (DeltaP) did not change the blood-brain barrier permeability in both acute hypertension and seizures.
Pharmacological Research 09/2001; 44(3):209-12. · 4.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osmotic and ionic balance in the central nervous system is especially regulated by solutes and water transport across the blood-brain barrier. The aim of this study was to investigate the effect of systemic hyperosmolarity on the blood-brain barrier permeability in both sexes after experimentally induced seizures. Eight groups of rats were studied: Group I: female control; Group II: male control; Group III: hyperosmotic female; Group IV: hyperosmotic male; Group V: non-hyperosmotic female + seizure; Group VI: non-hyperosmotic male + seizure; Group VII: hyperosmotic female + seizure; Group VIII: hyperosmotic male + seizure. In female rats with pentylenetetrazol-induced seizures, the extravasation of Evans-blue was greater in the brains of hyperosmotic animals than that in normal rats (P < 0.02). However, in male rats, the extravasation of Evans-blue was similar in the brains of hyperosmotic male rats and normal rats after seizure. Our results concluded that hyperosmotic female rats were shown to have a large increase in blood-brain barrier permeability in comparison to hyperosmotic male rats after pentylenetetrazol-induced seizures.
Pharmacological Research 05/2001; 43(5):469-72. · 4.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To understand the increased susceptibility of the development of serious complications to hypoosmotic hyponatremia in young females, we examined the resistance of blood brain barrier (BBB) permeability to water along with the synaptosomal Na(+),K(+)ATPase activity in both sexes of rats during acute water intoxication. Four groups of rats were used: Group I and II were normal female and male rats injected with only Evans-blue. Group III and IV were water intoxicated female and male rats respectively. BBB permeability in female rats was found to be increased following acute water intoxication. In contrast, synaptosomal Na(+),K(+)ATPase activities in both water intoxicated male and female rats were found significantly lower than those in control rats. But inhibition in enzyme activity in synaptosomes from water intoxicated female rats was more pronounced than those of corresponding male rats. Our results concluded that female sex steroids may be responsible for the highly significant decrease in synaptosomal Na(+),K(+)ATPase activity and increased BBB permeability in female rats following water intoxication.
Journal of Neuroscience Research 01/2001; 62(5):750-3. · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have examined the effect of antioxidants (vitamin E, and selenium) on the blood-brain barrier permeability during adreneline-induced acute hypertension in the female rats. The rats supplemented with nontoxic doses of sodium selenite in drinking water for three months or vitamin E was given intraperitoneally before adrenaline-induced acute hypertension. Evans-blue was used as a blood-brain barrier tracer. Mean values for Evans-blue dye were found to be 0.28 +/- 0.04 microg/g tissue in control animals and 1.0 +/- 0.2 microg tissue after adrenaline-induced acute hypertension (p < .01). Rats pretreated with selenium or vitamin E also showed macroscopic leakage of Evans-blue albumin after adrenaline injection i.e., there was no significant difference in protein extravasation between untreated and treated animals (p > .5). The mean value for Evans-blue dye was found to be 1.0 +/- 0.2 microg/g tissue in acute hypertension group, 0.9 +/- 0.2 microg/g tissue in selenium pretreated animals and 1.0 +/- 0.2 micrg/g tissue vitamin E injected animals after acute hypertension. The results show that antioxidants did not influence the blood-brain barrier breakdown during adrenaline-induced acute hypertension.
International Journal of Neuroscience 12/2000; 105(1-4):27-35. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The influence of the calcium channel blocker nifedipine plus bicuculline-induced seizures on the permeability of the blood-brain barrier to protein was studied in rats. Evans-blue was used as a blood-brain barrier tracer. Four groups of rats were studied. Group I: control, Group II: Nifedipine, Group III: bicuculline-induced seizure, Group IV: Nifedipine + seizure. The mean value for Evans-blue dye in the brain was found to be 0.23+/-0.03 mg/g in control animals and 0.32+/-0.06 mg/g in the group of all rats during nifedipine-induced hypotension. This difference between control and hypotensive animals was not statistically significant (p < 0.5). Mean value for Evans-blue dye in the brain was found to be 1.4+/-0.3 mg/g in bicuculline-induced seizure, and 0.73+/-40.2 mg/g in the group of nifedipine plus bicuculline-induced seizures. This difference between Group III and Group IV was found statistically significant (p < .01). The calcium channel blocker nifedipine significantly prevents the blood brain barrier disruption during bicuculline-induced seizure.
International Journal of Neuroscience 09/1999; 99(1-4):105-12. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The changes in the permeability of the blood-brain barrier (BBB) during bicuculline-induced seizures were investigated in ovariectomized female and orchidectomized male rats. The rats were anesthetized with diethyl ether. Evans blue, which was used as a BBB tracer, was injected into femoral vein 5 min before administering bicuculline to induce grandmal seizures. Ten groups of rats were studied: Group I: control female; Group II: control male; Group IIl: intact female + bicuculline; Group IV: intact male + bicuculline; Group V: ovariectomized female; Group VI: orchidectomized male; Group VII: ovariectomized female + bicuculline; Group VIII: orchidectomized male + bicuculline (1.2 mg/kg, i.v.); Group IX: ovariectomized female + estrogen + bicuculline; Group X: orchidectomized male + estrogen + bicuculline. Adult male and female rats were orchidectomized and ovariectomized 3 weeks before the experiments, or sham operated under general anesthesia. During bicucculline-induced seizures, the mean arterial blood pressure increased significantly in both intact and ovariectomized and orchidectomized rats. BBB lesions were present in 80 percent of intact female rats and 50 percent of ovariectomized rats after bicuculline-induced seizures. This difference between intact and ovariectomized rats was found to be significant (p < 0.01). There was no statistically significant change in the BBB permeability between intact and orchidectomized rats after convulsion. Generating seizures in both ovariectomized and orchidectomised rats, after administrating of estrogen, did not lead to any significant alteration in BBB permeability. Our results suggest that the extravasation of Evans blue albumin was most pronounced in the brain of intact female rats when compared to ovariectomized rats after bicuculline-induced seizures. After administrating estrogen, the decreased BBB permeability values of ovariectomised rats could not reach the values in intact rats.
Hormone and Metabolic Research 09/1998; 30(8):500-3. · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The asymmetrical breakdown of the blood-brain barrier to Evans-blue was studied in male and female rats during epileptiform seizures and in acute hypertension. The animals were divided into six groups. Group I: control female; Group II: control male; Group III: female + acute hypertension; Group IV: male + acute hypertension; Group V: female + seizure; Group VI: male + seizure. Asymmetric breakdown of the blood-brain barrier had been seen in female rats treated with pentylenetetrazol. Pentylenetetrazol-induced seizure produces less disruption of the blood-brain barrier in right cerebral hemisphere than in left cerebral hemisphere in female rats. There were no asymmetrical changes of blood-brain barrier permeability between the left and right hemispheres in acute hypertension in both sexes, and male rats treated with pentylenetetrazol.
Psychiatry Research 06/1998; 82(2):129-33. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An animal model for reversible blood-brain barrier disruption has been developed. Retrograde infusion of hyperthermic saline solution 43 degrees C into the left external carotid artery of normothermic, Wistar rats, reversibly increases cerebrovascular permeability to Evans-blue albumin in the left cerebral hemisphere. Isotonic saline solutions at 37 degrees C for group I and 43 degrees C for group II were infused for 30-s at a constant rate of 0.12 ml/s into the left external carotid artery. Evans-blue, the barrier tracer was administered intravenously either prior to or at intervals of 5, 30, 180, 360 min after the hyperthermic saline infusion under pentobarbital anesthesia. All animals receiving hyperthermic saline perfusion had disturbed blood-brain barrier permeability. Based on visual inspection, disruption grade in the left hemispheres of six of 11 animals was grade 3+. Mean values for Evans-blue dye were found to be 0.28 +/- 0.06 mg/g of tissue in left hemisphere after normothermic saline infusion (group I), and 2.41 +/- 0.5 mg/g of tissue in the same hemisphere after hyperthermic saline infusion (group II). The difference was found to be significant between group I and group II (p < 0.01). The increase in cerebrovascular permeability was temporary, even though Evans-blue albumin extravasation remained slightly elevated 3 h after infusion and was normal 6 h after infusion.
International Journal of Hyperthermia 01/1998; 14(4):395-401. · 2.59 Impact Factor