Selenium and Topiramate Modulates Brain Microsomal Oxidative Stress Values, Ca2+-ATPase Activity, and EEG Records in Pentylentetrazol-Induced Seizures in Rats

It has been suggested that oxidative stress products play an important role in the etiology of epilepsy. We investigated the effects of selenium (Se) administration on topiramate (TPM)- and pentylentetrazol (PTZ)-induced brain toxicity in rats. Forty male Wistar rats were divided into five equal groups. The first and second groups were used as the control and PTZ groups, respectively. TPM, 50 mg, and Se, 0.3 mg, were administered to rats constituting the third and fourth groups, respectively, for 7 days. The combination of 50 mg TPM and Se was given to animals in the fifth group for 7 days. At the end of 7 days all groups except the first received a single dose of PTZ. Brain cortex samples were taken at 3 h of PTZ administration. PTZ resulted in a significant increase in brain cortex and microsomal lipid peroxidation (LP) levels, number of spikes, and epileptiform discharges on the EEG, although brain cortex vitamin E, brain cortex and microsomal reduced glutathione (GSH), and microsomal calcium (Ca) levels, Ca(2+)-ATPase activities, and latency to first spike on the EEG were decreased by PTZ. LP, GSH, vitamin E, and Ca levels and Ca(2+)-ATPase activities were increased by both Se and TPM, although vitamin A and C concentrations were increased by Se only. There were no effects of TPM and Se on brain cortex and microsomal glutathione peroxidase, brain cortex nitric oxide, or beta-carotene levels. In conclusion, TPM and selenium caused protective effects on PTZ-induced brain injury by inhibiting free radical production, regulating calcium-dependent processes, and supporting the antioxidant redox system.     

Venlafaxine Modulates Depression-Induced Oxidative Stress in Brain and Medulla of Rat

Venlafaxine is an approved antidepressant that is an inhibitor of both serotonin and norepinephrine transporters. Medical treatment with oral venlafaxine can be beneficial to depression due to reducing free radical production in the brain and medulla of depression- induced rats because oxidative stress may a play role in some depression. We investigated the effect of venlafaxine administration and experimental depression on lipid peroxidation and antioxidant levels in cortex brain, medulla and erythrocytes of rats. Thirty male wistar rats were used and were randomly divided into three groups. Venlafaxine (20 mg/kg) was orally supplemented to depression-induced rats constituting the first group for four week. Second group was depression-induced group although third group was used as control. Depressions in the first and second groups were induced on day zero of the study by chronic mild stress. Brain, medulla and erythrocytes samples were taken from all animals on day 28. Depression resulted in significant decrease in the glutathione peroxidase (GSH-Px) activity and vitamin C concentrations of cortex brain, glutathione (GSH) value of medulla although their levels were increased by venlafaxine administration to the animals of depression group. The lipid peroxidation levels in the three tissues and nitric oxide value in cortex brain elevated although their levels were decreased by venlafaxine administration. There were no significant changes in cortex brain vitamin A, erythrocytes vitamin C, GSH-Px and GSH, medulla vitamin A, GSH and GSH-Px values. In conclusion, cortex brain within the three tissues was most affected by oxidative stress although there was the beneficial effect of venlafaxine in the brain of depression-induced rats on investigated antioxidant defenses in the rat model. The treatment of depression by venlafaxine may also play a role in preventing oxidative stress. Abstract of the paper was submitted in 1st Ion Channels and Oxidative Stress Congress, 14–16 September 2006, Isparta, Turkey.     

Topiramate modulates hippocampus NMDA receptors via brain Ca2+ homeostasis in pentylentetrazol-induced epilepsy of rats

Background: Increase in neuronal Ca²⁺, activation of hippocampus N-methyl-D-aspartate receptor (NMDAR) and defects in enzymes such as brain cortex microsomal membrane Ca²⁺-ATPase (MMCA) are thought to play a role in epilepsy. Topiramate (TOP) is a novel drug with broad antiepileptic effect, and its effect on brain cortex MMCA is not known. We investigated effects of TOP on pentylentetrazol (PTZ)-induced MMCA activity and NMDAR subunits in rat brain.

Materials and methods: Thirty-two rats were randomly divided into four equal groups. The first group and second groups were used for the control and PTZ groups, respectively. 50 and 100?mg TOP were administered to rats constituting the third (TOP50) and fourth (TOP100) groups for 7 days, respectively. At the end of 7 days, all groups except the first received a single dose PTZ. Brain and hippocampus samples were taken at 3?hrs after PTZ administration.

Results: The microsomal MMCA activity was lower in the PTZ group than in control although the MMCA activities were higher in the treatment group than in PTZ group. Brain cortex total calcium levels, the hippocampus NMDAR 2A and 2B subunit concentrations were higher in the PTZ group than in control although their concentrations were decreased by TOP50 and TOP100 administration. Total brain cortex calcium and hippocampus NMDAR 2A and 2B subunit concentrations were higher in TOP100 group than in TOP50 group.

Conclusion: The two doses of TOP modulated MMCA activity, total brain cortex calcium and hippocampus NMDAR 2A and 2B subunit concentrations in the epileptic rats.     

Effect of Feeding Xenobiotics on Serum High Density Lipoprotein and Apolipoprotein A-I in Rats

The effects on serum cholesterol level were examined in rats fed on various xenobiotics. The hypercholesterolemia induced by polychlorinated biphenyls (PCB) was characterized in rats, from which lipoproteins were isolated by ultracentrifugation. A dietary addition of 0.03% PCB, 0.3% chloretone, 0.1% aminopyrine, or 0.2% 2,6-di-tert-butyl-p-cresol (BHT) resulted in a significant increase in serum cholesterol, although the chemical structure of each of these xenobiotics was different. The serum cholesterol level was markedly increased by one month of PCB feeding, the effect of PCB on the serum phospholipid level being similar. The serum triglyceride level transiently increased within 7 days of feeding with PCB diet. PCB feeding resulted in the elevation of all lipoproteins, including VLDL, LDL, HDL₁, and HDL₂, a marked increase being observed in HDI₁. Both HDL₁ and HDL₂ isolated from PCB-treated rats contained more apolipoprotein A-I (apo A-I) and less apo E than normal. VLDL isolated from PCB-treated rats had more cholesterol and apo E, but less apo C than that of the control animals. These data demonstrate that PCB feeding resulted in increased VLDL rich in cholesterol and apo E, and increased HDL rich in apo A-I. This experimentally induced hypercholesterolemia resulting in apo A-I-rich HDL would be a useful model for investigating the metabolism of apo-A-I and HDL.     

钙调蛋白及其调节酶PDE在鸡脑胚胎发育过程中的变化

钙调蛋白(CaM)参与脑中多种细胞过程的调节,推测它与大脑的分化发育有关。本实验研究了鸡脑从胚胎早期(原基)至大脑成熟各发育阶段可溶部分的CaM及其调节酶——环核苷酸磷酸二酯酶(PDE)的含量或活力变化。未经孵育的鸡胚中检测不出CaM,在孵育3—14天的胚脑中CaM含量逐渐增加:总CaM增加了3倍,活性CaM增加了4倍;而且在鸡脑细胞分裂分化最活跃的期间(皮质和髓质形成期间,即孵育8—14天),活性CaM的增加尤为显著(增加近3倍)。提示CaM与脑细胞的分裂分化有关。PDE的活力出现晚于CaM5天,随着胚龄增加,不断上升,提示它与脑细胞的分裂分化无直接关系,可能与大脑的功能活动有关。本实验还研究了鸡脑发育期中可逆性钙结合蛋白的变化。     

妊娠期腹腔注射多氯联苯对大鼠生长发育的影响

将50只同期怀孕的大鼠分为5组,在怀孕第7—18d,每天给两组大鼠腹腔分别注射1和20mg／kg体重2,2’,4,4’-四氯联苯(PCB47);给另两组分别注射0．25和1mg／kg体重3,3’,4,4’-四氯联苯(PCB77);对照组注射0．1mL芝麻油。幼鼠出生时记录每窝产仔数和性比;出生后每隔7d称体重直到第119d;出生后第15天时检查幼鼠的睁眼率。与对照组相比,PCB47和PCB77所有剂量组每窝产仔数和性比无显著差异;PCB47(20g／kg体重组)和PCB77(两个剂量组)雌幼鼠肛门一生殖孔距离显著增加,出生后15d幼鼠的睁眼率显著降低;PCB77(1mg／kg体重组)雄幼鼠从出生后第35至119天体重显著降低。提示PCB77主要影响雄鼠的生长发育。     

The pentylenetetrazole-kindling model of epilepsy in SAMP8 mice: behavior and metabolism

This work describes a novel epilepsy model, combining pentylenetetrazole (PTZ) kindling with the senescence-accelerated mouse P8 (SAMP8) a model for aging. The 2- and 8-month-old SAMP8 mice were treated with PTZ, phenobarbital plus PTZ or saline every 48 h during a period of 40 days. Both 2- and 8-month-old PTZ-kindled mice showed a behavioral pattern that was very similar to severe chronic epilepsy with secondary generalized seizures. Two out of six 8-month-old animals died in the PTZ group. Interestingly, atypical absence seizures were limited to the 8-month-old PTZ group. Furthermore, 8-month-old mice were more sensitive to the sedative effect of phenobarbital. The concentrations of several amino acids were examined by HPLC. Lower levels of amino acids were found in the 8-month-old compared to the 2-month-old control animals. No biochemical changes were observed between the groups of 2-month-old animals, while in the 8-month-old animals both treatment groups showed significantly higher concentrations of GABA, glutamine and glutathione. Thus, it could be shown that cerebral metabolism of 8-month-old SAMP8 mice was more sensitive to PTZ and phenobarbital than metabolism of 2-month-old mice. Furthermore, it is suggested that glutamate metabolism in brains of 8-month-old SAMP8 mice is altered and that excessive glutamate is transformed, in considerable amounts, into glutamate related metabolites, possibly in astrocytes.     

Evaluation of the effect of cafeteria diet on the kidney Na,K-ATPase activity,and oxidative stress

In this study, renal tissue, subdivided into the cortex and medulla of Wistar rats subjected to a cafeteria diet (CAF) for 24 days or to normal diet, was used to analyze whether the renal enzyme Na,K-ATPase activity was modified by CAF diet, as well as to analyze the α1 subunit of renal Na,K-ATPase expression levels. The lipid profile of the renal plasma membrane and oxidative stress were verified. In the Na,K-ATPase activity evaluation, no alteration was found, but a significant decrease of 30% in the cortex was detected in the α1 subunit expression of the enzyme. There was a 24% decrease in phospholipids in the cortex of rats submitted to CAF, a 17% increase in cholesterol levels in the cortex, and a 23% decrease in the medulla. Lipid peroxidation was significantly increased in the groups submitted to CAF, both in the cortical region, 29%, and in the medulla, 35%. Also, a reduction of 45% in the glutathione levels was observed in the cortex and medulla with CAF. CAF showed a nearly two-fold increase in glutathione peroxidase (GPX) activity in relation to the control group in the cortex and a 59% increase in the GPx activity in the medulla. In conclusion, although the diet was administered for a short period of time, important results were found, especially those related to the lipid profile and oxidative stress, which may directly affect renal function.     

Topiramate and Vitamin E Modulate the Electroencephalographic Records,Brain Microsomal and Blood Antioxidant Redox System in Pentylentetrazol-Induced Seizure of Rats

We investigated the effects of vitamin E and topiramate (TPM) administrations on pentylentetrazol (PTZ)–induced blood and brain toxicity in rats. Forty rats were randomly divided into five equal groups. The first and second groups were used for the control and PTZ groups, respectively. Fifty or 100 mg TPM were administered to rats constituting the third and fourth groups for 7 days, respectively. The TPM and vitamin E combination was given to animals in the fifth group. At the end of 7 days, all groups except the first received a single dose of PTZ. Blood and brain samples were taken at 3 hrs after PTZ administration. Lipid peroxidation levels of plasma, erythrocyte, brain cortex and brain microsomal fraction; nitric oxide levels of serum; and the number of spikes and epileptiform discharges of the EEG were increased by PTZ administration. Plasma and brain vitamin E concentration, erythrocyte glutathione peroxidase (GSH-Px) activity and latency to first spike of the EEG were decreased by PTZ. Plasma lipid peroxidation levels in the third group and plasma and erythrocyte lipid peroxidation levels in the fifth group were decreased compared to the second group, whereas brain vitamin C, vitamin E, erythrocyte GSH-Px and reduced glutathione (GSH) values increased in the fifth group. Brain microsomal GSH levels and EEG records in the third, fourth and fifth groups were restored by the TPM and vitamin E treatment. In conclusion, TPM and vitamin E seems to have protective effects on PTZ-induced blood and brain toxicity by inhibiting free radicals and supporting the antioxidant redox system.     

Effects of naloxone-precipitated withdrawal after a single dose of morphine on catecholamine concentrations in guinea-pig brain

The effect of naloxone-precipitated withdrawal after acute morphine was studied on the concentrations of noradrenaline (NA), 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and on the metabolite/parent amine ratios MHPG/NA, DOPAC/DA and HVA/DA, in eight regions of the guineapig brain. Guinea-pigs were treated with a single dose of morphine sulphate (15 mg/kg s.c.) or saline (control) and 2h later with naloxone hydrochloride (15 mg/kg s.c.) to precipitate withdrawal. The animals were decapitated at 0.5 h or 1 h after naloxone injections and their brains analysed for monoamine concentrations by HPLC-ECD. At 0.5 h after naloxone-precipitated withdrawal NA and MHPG levels, and the MHPG/NA ratio, were increased in the hypothalamus, and the NA levels were increased in the hypothalamus, medulla/pons and cortex 1 h after naloxone. Naloxoneprecipitated withdrawal also produced increased DA metabolism in the cortex, midbrain and medulla 0.5 h later, and in the cortex, hypothalamus and striatum 1 h later. Hence naloxone-precipitated withdrawal from acute morphine treatment produced a complex pattern of increased synthesis and metabolism of NA and DA which varied over time and with the brain region examined.     

Capparis ovata Modulates Brain Oxidative Toxicity and Epileptic Seizures in Pentylentetrazol-Induced Epileptic Rats

It has been widely suggested that oxidative stress products play an important role in the pathophysiology of epilepsy. Capparis ovata (C. ovata) may useful treatment of epilepsy because it contains antioxidant flavonoids. The current study was designed to determine the effects of C. ovata on lipid peroxidation, antioxidant levels and electroencephalography (EEG) records in pentylentetrazol (PTZ)-induced epileptic rats. Thirty-two rats were randomly divided into four groups. First group was used as control although second group was PTZ group. Oral 100 and 200 mg/kg C. ovata were given to rats constituting the third and fourth groups for 7 days before PTZ administration. Second, third and forth groups received 60 mg/kg PTZ for induction of epilepsy. Three hours after administration of PTZ, EEG records, brain cortex and blood samples were taken all groups. The lipid peroxidation levels of the brain cortex, number of spikes and epileptiform discharges of EEG were higher in PTZ group than in control and C. ovata group whereas they were decreased by C. ovata administration. Vitamin A, vitamin C, vitamin E and β-carotene concentrations of brain cortex and latency to first spike of EEG were decreased by the PTZ administration although the brain cortex and plasma vitamin concentrations, and brain cortex and erythrocyte glutathione and glutathione peroxidase values were increased in PTZ + 100 and PTZ + 200 mg C. ovata groups. In conclusion, C. ovata administration caused protection against the PTZ-induced brain oxidative toxicity by inhibiting free radical and epileptic seizures, and supporting antioxidant redox system.     

Response to polychlorinated biphenyls of marine phytoplankton isolates cultured under natural conditions.

Polychlorinated biphenyls (PCB) at a concentration of 10 mug/liter substantially but temporarily suppressed the growth rate and photosynthesis of two species of Thalassiosira recently isolated from Long Island Sound and grown in dialysis membrane bags suspended in the tidal channel of an estuarine marsh. Inhibition of carbon fixation was apparently due to reduced levels of chlorophyll a per PCB-treated cell, but no significant loss of function per unit of existing chlorophyll a was observed. Cell concentrations in all size classes (3.2- to 18.6-mum-equivalent spherical diameters) were markedly lower in PCB-treated cultures, with toal biomass equaling only 30% of that in control cultures throughout the experiment.     

Effect of interferon-alpha on tyrosine hydroxylase and catecholamine levels in the brain of rats

We investigated the effect of interferon on tyrosine hydroxylase (TH) and catecholamine levels in the brains of 12-week-old male Wistar rats. Interferon-alpha (300,000 IU/kg/day, s.c.) was administered to rats for 7 days. Locomotor activity of interferon-alpha-treated rats was significantly lower than that of control rats. Norepinephrine and dopamine levels and TH activities in the cerebral cortex, hypothalamus and medulla oblongata of interferon-alpha-treated rats were significantly higher than those of control rats. Norepinephrine and dopamine levels and TH activities in the thalamus and hippocampus were not different between interferon-alpha treated and control rats. These results suggest that interferon-alpha-induced depression may be related to change in the catecholamine synthetic pathway in the central nervous system.     

Cyclooxygenase-1 and cyclooxygenase-2 expression in rat kidney and adrenal gland after stimulation with systemic lipopolysaccharide

Cyclooxygenase-2 (COX-2) is a recently discovered isoform of cyclooxygenase that is inducible by various types of inflammatory stimuli. Although this enzyme is considered to play a major role in inflammation processes by catalyzing the production of prostaglandins, the precise location, distribution, and regulation of prostaglandin synthesis remains unclear in several tissues. Using in situ hybridization histochemistry, we investigated the induction of COX-1 and COX-2 mRNA expression after systemic administration of a pyrogen, lipopolysaccharide (LPS), in kidney and adrenal gland in the rat. The COX-2 mRNA signals dramatically increased 1 h after LPS treatment in the kidney outer medulla and adrenal cortex, where almost no or little expression was observed in nontreated animals, and returned to control levels within 24 h. COX-2 mRNA levels increased in the kidney inner medulla 6 h after treatment. There was also a significant increase in mRNA levels in the kidney cortex and adrenal medulla. On the other hand, COX-1 mRNA levels did not show any detectable changes except in the kidney inner medulla, where a significant downregulation of mRNA expression was observed after LPS treatment. Light and electron immunocytochemistry using COX-2 antibodies showed that strong COX-2 immunoreactivity was localized to certain cortical cells of the thick ascending limb of Henle. In addition, based on double-staining with antiserum to nitric oxide synthase (NOS) four further cell populations could be identified in kidney cortex, including weakly COX-2-positive, NOS-positive macula densa cells. After LPS treatment, changes in COX-2 immunoreactivity could be observed in interstitial cells in the kidney medulla and in inner cortical cells in the adrenal gland. These results show that COX-2 is a highly induced enzyme that can be up-regulated in specific cell populations in kidney and adrenal gland in response to inflammation, leading to the elevated levels of prostaglandins seen during fever. In contrast COX-1 mRNA levels remained unchanged in this experimental situation, except for a decrease in kidney inner medulla.     

Postmortem biochemical indices of antemortem hemorrhagic shock

The purpose of this study was to determine if the perturbations in two glycolytic metabolites that occur during hemorrhagic shock can be used as discriminatory postmortem indicators of death resulting from severe hemorrhagic shock. Two groups of male albino Sprague-Dawley rats were hemorrhaged by withdrawing either 40% (Group I) or 45% (Group II) of the total blood volume. Glycogen and lactate concentrations were determined at 0 and 48 hr postmortem in the following tissues and organs: diaphragm, heart, liver, kidney cortex, and kidney medulla. The differences in lactate and glycogen in Group I at 0 hr were not significantly different from the nonhemorrhaged controls, with the exception of the lower liver glycogen concentration (58% of control). In Group II glycogen concentration was significantly reduced at 0 hr in the diaphragm (70% of control), liver (37%), and kidney medulla (55%). Lactate concentration was higher in all tissues examined by 270-640%; within 48 hr all tissues for both control and hemorrhaged animals had declined to baseline levels of glycogen concentration, whereas lactate levels had increased as much as 34-fold. There were no highly significant differences in glycogen at 48 hr between the control and hemorrhaged groups. In Group II the lactates were similar for both the control and hemorrhaged animals with the exception of the higher concentrations in the kidney cortex (54%) and medulla (41%). It was concluded from these findings that although significant metabolic perturbations are present at the time of death due to hemorrhage these differences do not persist up to 48 hr postmortem, with the possible exception of the kidney lactate concentrations.     

Dietary supplementation with acetyl-l-carnitine in seizure treatment of pentylenetetrazole kindled mice

In spite of the availability of new antiepileptic drugs a considerable number of epilepsy patients still have pharmacoresistant seizures, and thus there is a need for novel approaches. Acetyl-l-carnitine (ALCAR), which delivers acetyl units to mitochondria for acetyl-CoA production, has been shown to improve brain energy homeostasis and protects against various neurotoxic insults. To our knowledge, this is the first study of ALCAR's effect on metabolism in pentylenetetrazole (PTZ) kindled mice. ALCAR or the commonly used antiepileptic drug valproate, was added to the drinking water of mice for 25days, and animals were injected with PTZ or saline three times a week during the last 21days. In order to investigate ALCAR's effects on glucose metabolism, mice were injected with [1-(13)C]glucose 15min prior to microwave fixation. Brain extracts from cortex and the hippocampal formation (HF) were studied using (1)H and (13)C NMR spectroscopy and HPLC. PTZ kindling caused glucose hypometabolism, evidenced by a reduction in both glycolysis and TCA cycle turnover in both brain regions investigated. Glutamatergic and GABAergic neurons were affected in cortex and HF, but the amount of glutamate was only reduced in HF. Slight astrocytic involvement could be detected in the cortex. Interestingly, the dopamine content was increased in the HF. ALCAR attenuated the PTZ induced reduction in [3-(13)C]alanine and the increase in dopamine in the HF. However, TCA cycle metabolism was not different from that seen in PTZ kindled animals. In conclusion, even though ALCAR did not delay the kindling process, it did show some promising ameliorative effects, worthy of further investigation.     

Enantioselective disposition of PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl) in C57BL/6 mice after oral and intraperitoneal administration

Studies of xenobiotic disposition in rodents often employ experimental designs using differing routes of administration. In an effort to investigate the effects of route of administration on enantioselective disposition of xenobiotics, a chiral polychlorinated biphenyl (PCB), racemic PCB 136, was administered as a single dose (50 mg/kg body weight) to male or female C57BL/6 mice either orally or via intraperitoneal injection. Mice were sacrificed after either 3 or 6 days, and blood and organs were collected for PCB analysis. Intraperitoneal injection of PCB 136 produced statistically higher PCB levels in blood and organs than did the oral administration. Tissue levels were higher after 3 days than those after 6 days. Enantioselective analysis showed that (+)-PCB 136 was enriched in most organs, with the most pronounced enrichment found in the liver and the brain of animals dosed orally or by intraperitoneal injection, respectively. Significantly higher retained enantiomeric fractions of PCB 136 were found in the oral treatment groups compared with those found in intraperitoneal treatment groups, possibly as a result of the lower PCB levels in oral treatment groups. Therefore, the choice of administration route may well have implications for the enantioselective disposition of PCB 136 and other chiral substances.     

GH administration and renal IGF-I system in arthritic rats

Experimental arthritis in rats results in a growth failure and a decrease in circulating and hepatic concentrations of insulin-like growth factor I (IGF-I). Renal damage has also been reported in arthritic rats. The aim of this study was 1) to analyse if alterations in the IGF-I system in the kidney occurs in adjuvant-induced arthritis and 2) to analyse if recombinant human GH (rhGH) administration is able to reverse these effects. Male Wistar rats were injected with complete Freund's adjuvant or vehicle and 22 days later they were killed. Arthritis increased serum creatinine levels, relative kidney weight and IGF-I concentrations in this organ. In a second experiment, arthritic and control rats received rhGH (3 UI/Kg sc) or 250 microl saline from day 14, after adjuvant or vehicle injection, until day 22. IGF-I concentrations were higher in both the renal cortex and medulla of arthritic rats. In contrast, kidney IGF-I mRNA was lower in both areas of arthritic animals. GH treatment significantly decreased serum creatinine levels and IGF-I concentrations in the kidney cortex and medulla of arthritic rats. However, the administration of rhGH to arthritic animals significantly increased the IGF-I gene expression in both the renal cortex and medulla. Serum and kidney concentrations of IGF-I binding proteins (IGFBPs) were increased in arthritic animals and they were reduced by GH administration. CONCLUSION: These data suggest that experimental arthritis causes renal dysfunction and GH treatment can ameliorate this effect.     

Cysteamine normalizes cerebral somatostatin level and binding in pentylenetetrazol-kindled rats

Rats were kindled by intraperitoneal injection of pentylenetetrazol (PTZ) (30 mg/Kg) every 48 h. Once kindled, some of the animals received a single injection of cysteamine (200 mg/Kg). Somatostatin-like immunoreactivity (SLI) and 125 I-Tyr11-somatostatin binding were measured in the frontoparietal cortex and hippocampus of the two experimental groups and the control rats. After PTZ kindling the following was observed: 1) SLI content was increased in the two areas; 2) Somatostatin receptor affinity decreased in the frontoparietal cortex and was unaltered in the hippocampus; 3) The number of somatostatin receptors decreased in the hippocampus and was unaltered in the frontoparietal cortex. Cysteamine, an agent which depletes brain somatostatin and suppresses kindled seizures in PTZ-treated rats, reversed the altered SLI levels and binding in these rats.     

Effects of Nigella sativa on apoptosis and GABAA receptor density in cerebral cortical and hippocampal neurons in pentylenetetrazol induced kindling in rats

We investigated the effects of Nigella sativa on apoptosis and gamma-aminobutyric acid (GABA_A) receptor density in cerebral cortical and hippocampal neurons in a pentylenetetrazol (PTZ)-induced kindling model in rats. The PTZ kindling model was produced by injecting PTZ in subconvulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22 and 24 of the study into animals of PTZ treated (PTZ) and PTZ + N. sativa treated (PTZ + NS) groups. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the PTZ + NS group were treated also with a 10 mg/kg methanolic extract of N. sativa 2 h before each PTZ injection. Rats in the control group were treated with 4 ml/kg saline. The number of neurons that expressed GABA_A receptors in the hippocampus and cerebral cortex of rats in the PTZ and PTZ + NS groups increased significantly. There was no significant difference in the number of GABA_A receptors between the PTZ and PTZ + NS groups. GABA_A receptor density of the neurons in the cerebral cortex, but not hippocampus, was increased in PTZ group compared to controls. We observed a significant increase in the number of apoptotic neurons in the cerebral cortex of rats of both the PTZ and PTZ + NS groups compared to controls. We observed a significant decrease in the number of the apoptotic neurons in the cerebral cortex of rats in the PTZ + NS group compared to the PTZ group. N. sativa treatment ameliorated the PTZ induced neurodegeneration in the cerebral cortex as reflected by neuronal apoptosis and neuronal GABA_A receptor frequency.