Brain derived neurotrophic factor modification of epileptiform burst discharges in a temporal lobe epilepsy model

Introduction: Transforming Growth Factor-Beta 1 [TGF-beta1] is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke [IS], by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-beta1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-beta1 and susceptibility to IS

Methods: Male Wistar rats were divided into sham [receiving phosphate buffered saline within dorsal hippocampus], pilocarpine [epileptic model of TLE], single injection BDNF [epileptic rats which received single high dose of BDBF within dorsal hippocampus], and multiple injections BDNF [epileptic rats which received BDNF in days 10, 11, 12, and 13 after induction of TLE] groups. Their electrocorticogram was recorded and amplitude, frequency, and duration of spikes were evaluated

Results: Amplitude and frequency of epileptiform burst discharges were significantly decreased in animals treated with BDNF compared to pilocarpine group

Conclusion: Our findings suggested that BDNF may modulate the epileptic activity in the animal model of TLE. In addition, it may have therapeutic effect for epilepsy. More studies are necessary to clarify the exact mechanisms of BDNF effects

Antioxidant role of oleuropein on midbrain and dopaminergic neurons of substantia nigra in aged rats

Oleuropein is a phenolic compound which is present in the olive leaf extract. The purpose of the present study was to investigate the neuroprotective effect of oleuropein as an antioxidant agent on the substantia nigra in aged rats. Twenty 18-month-old Wistar rats [450-550 g] were randomly divided into control and experimental groups. The experimental group received a daily single dose of 50 mg/kg of oleuropein by oral gavage for 6 months. The control group received only distilled water. All rats were sacrificed two hours after the last gavage and the brains were removed and midbrains were cut. One part of the midbrains were homogenized and centrifuged. The tissue supernatant was assayed for lipid peroxidation [LPO] and antioxidant enzyme activities. The other part of midbrains fixed and embedded in paraffin, then processed for Nissl and immunohistochemistry [IHC] staining. Data was analyzed using SPSS by t-test. Differences were considered significant for P<0.05. The level of LPO in midbrain of the rats was decreased significantly in the experimental group, but superoxide dismutase, catalase and glutathione peroxidase activities were increased in experimental group compared to control group [P<0.05]. Morphometric analyses showed significantly that the experimental group had more neurons in substantia nigra pars compacta [SNc] either in Nissl or IHC staining when compared to control [P<0.05]. The results of the present study indicate that treatment of the old rats with oleuropein reduces the oxidative damage in SNc by increasing the antioxidant enzyme activities

Transforming growth factor -alpha improves memory impairment and neurogenesis following ischemia reperfusion

Stroke is most important cause of death and disability in adults. The hippocampal CA1 and sub-ventricular zone neurons are vulnerable to ischemia that can impair memory and learning functions. Although neurogenesis normally occurs in the dentate gyrus [DG] of the hippocampus and sub-ventricular zone [SVZ] following brain damage, this response is unable to compensate for severely damaged areas. This study aims to assess both neurogenesis and the neuroprotective effects of transforming growth factor-alpha [TGF-alpha] on the hippocampus and SVZ following ischemia-reperfusion. In this experimental study, a total of 48 male Wistar rats were divided into the following groups: surgical [n=12], phosphate buffered saline [PBS] treated vehicle shams [n=12], ischemia [n=12] and treatment [n=12] groups. Ischemia was induced by common carotid occlusion for 30 minutes followed by reperfusion, and TGF-alpha was then injected into the right lateral ventricle. Spatial memory was assessed using Morris water maze [MWM]. Nestin and Bcl-2 family protein expressions were studied by immunohistochemistry [IHC] and Western blot methods, respectively. Finally, data were analyzed using Statistical Package for the Social Sciences [SPSS, SPSS Inc., Chicago, USA] version 16 and one-way analysis of variance [ANOVA]. TGF-alpha injection significantly increased nestin expression in both the hippocampal DG and SVZ areas. TGF-alpha treatment caused a significant decrease in Bax expression and an increase in Bcl-2 anti-apoptotic protein expression in the hippocampus. Our results showed a significant increase in the number of pyramidal neurons. Memory also improved significantly following TGF-alpha treatment. Our findings proved that TGF-alpha reduced ischemic injury and played a neuroprotective role in the pathogenesis of ischemic injury

assay of bax and Bcl2 expression in mice hippocampus following ischemia-reperfusion treatment with CoQ10

Preliminary studies confirmed reduction of cell death following treatment with antioxidants. According to this finding we investigated the relationship between consumption of CoQ10 and expression of bax and bcl2 in hippocampus ischemia that this expression related to cell programmed death. We studied the protective role of CoQ10 against ischemia-reperfusion. Experimental design includes four groups: intact [N=7], ischemic control [N=7], sham control [N=7] and treatment groups with CoQ10 [N=7]. The mice [treatment group] treated with CoQ10 as Pre-Treatment for a week. Then, ischemia induced by common carotid artery ligation and following the reduction in inflammation [a week] the treatment group post-treated with CoQ10 for a week. Nissl staining applied to counting necrotic cells of hippocampus and the western blotting performed to measurement the bax and bcl2 expression. Tunnel kit was used to quantify apoptotic cell death while to short term memory scale, we apply Y-maze. Cell death was significantly lower when mice treated with CoQ10. Bax expression was significantly high in ischemic group but in treatment group was less and reversely the bcl2 expression in ischemic group was lower than treatment and vehicle groups. The memory test results were consistent with cell death results. Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQ10 intake significantly reduced cell death and decreased memory loss. with prevent of expression of bax and increase in expression of bcl2

[Effect of pentoxifylline on hepatocytes' damages due to administration of ecstasy in Wistar rat]

Ecstasy is a psychoactive, hallucinogen drug and a member of amphetamines family and is used commonly worldwide. Ecstasy overdose leads to restlessness, anxiety, hallucination, cardiovascular disorders and liver toxicity. Recently, the use of vasodilators, such as pentoxifylline [PTX], is one of the new strategies for protection against liver lesions caused by some substances such as alcohol consumption. There are few studies about the protective effect of pentoxifylline on liver damages due to MDMA long administration. Therefore, a comprehensive study on the protective effect of pentoxifylline on liver lesions caused by prolonged use of ecstasy seems to be necessary. This experimental study was performed on five groups: control, Ecstasy [7.5 mg/kg], Experimental 1 [100 mg/kg PTX simultaneously with the last dose of Ecstasy], experimental 2 [100 mg/kg PTX a week before Ecstasy injection], and vehicle [normal saline] groups [n=25]. After two weeks, animals were killed and their livers were prepared for histological studies [H and E method] and TUNEL technique for investigating of apoptotic bodies. The apoptotic bodies and hepatocytes lesions in experimental group 1 were lower than the other groupsm except control. It seems that the use of pentoxifylline after consumption of pure ecstasy can decrease tissue damage and prevent the induction of apoptosis in rat liver

role of the A2A receptor in cell apoptosis caused by MDMA

Ecstasy, also known as 3, 4-methylenedioxymethamphetamine [MDMA], is a psychoactive recreational hallucinogenic substance and a major worldwide recreational drug. There are neurotoxic effects observed in laboratory animals and humans following MDMA use. MDMA causes apoptosis in neurons of the central nervous system [CNS]. Withdrawal signs are attenuated by treatment with the adenosine receptor [A2A receptor]. This study reports the effects of glutamyl cysteine synthetase [GCS], as an A2A receptor agonist, and succinylcholine [SCH], as an A2A receptor antagonist, on Sprague Dawley rats, both in the presence and absence of MDMA. In this experimental study, we used seven groups of Sprague Dawley rats [200-250 g each]. Each group was treated with daily intraperitoneal [IP] injections for a period of one week, as follows: i. MDMA [10 mg/kg]; ii. GCS [0.3 mg/kg]; iii. SCH [0.3 mg/kg]; iv. GCS + SCH [0.3 mg/kg each]; v. MDMA [10 mg/kg] + GCS [0.3 mg/kg]; vi. MDMA [10 mg/kg] + SCH [0.3 mg/kg]; and vi. normal saline [1 cc/kg] as the sham group. Bax [apoptotic protein] and Bcl-2 [anti-apoptotic protein] expressions were evaluated by striatum using RT-PCR and Western blot analysis. There was a significant increase in Bax protein expression in the MDMA+SCH group and a significant decrease in Bcl-2 protein expression in the MDMA+SCH group [p<0.05]. A2A receptors have a role in the apoptotic effects of MDMA via the Bax and Bcl-2 pathways. An agonist of this receptor [GCS] decreases the cytotoxcity of MDMA, while the antagonist of this receptor [SCH] increases its cytotoxcity

Nitric oxide is necessary for diazoxide protection against ischemic injury in skeletal muscle

Ischemia reperfusion injury [IR injury] is a common problem in clinical conditions. Researches have frequently revealed that ATP- sensitive potassium [K[ATP]] channels and nitric oxide plays a role in protection against ischemic injury in skeletal muscle. The present study aimed at evaluating the possible link between this two pathways. Sixty-eight male wistar rats, were pretreated with saline, diazoxide [K[ATP] opener; 45 mg/Kg, IP], glibenclamide [K[ATP] inhibitor; 5 mg/Kg], or L-NAME [iNOS inhibitor; 20 mg/Kg, IP] before 3 h ischemia and 2 h reperfusion. Activities of antioxidant enzymes superoxide dismutase [SOD] and catalase [CAT], and the level of malondialdehyde [MDA] and expression of iNOS were measured in muscle tissue. Tissue MDA content was significantly increased by IR [p < 0.001]. Diazoxide significantly decreased the IR-induced elevation of tissue MDA level [p < 0.05] and Glibenclamide increased MDA [p < 0.05 vs. IR group]. L-NAME inhibited the effect of diazoxide on decreasing MDA [p < 0.01 vs., diazoxide+IR group] and IR decreased the activity of SOD and CAT [p < 0.01], while pretreatment with diazoxide increased activity of SOD and CAT [p < 0.01]. Glibenclamide decreased SOD and CAT activity after IR [p < 0.05]. L-NAME pretreatment in diazoxide-treated rats abolished the effect of diazoxide on increasing the activity of SOD and CAT [p < 0.05 vs. Diaz+IR]. Expression of iNOS was increased by IR [p < 0.01 vs. Sham group]. Diazoxide significantly decreased iNOS expression after IR [p < 0.05 vs. IR]. L-NAME significantly decreased iNOS expression after IR [p < 0.01] in diazoxide-treated rats [p < 0.01 vs. Diaz+IR]

Coenzyme Q10 protects hippocampal neurons against ischemia/ reperfusion injury via modulation of Bax/Bcl-2 expression

Preliminary studies have confirmed reduction in cell death following treatment with antioxidants. According to this finding we study the relationship between consumption of CoQ10 and expression of Bax and Bcl2 in hippocampus following ischemia/reperfusion as proteins involved in cell programmed death or apoptosis. We studied the protective role of CoQ 10 against ischemia-reperfusion. Experimental design includes four groups: intact, ischemic control, sham control and treatment group with CoQ10. The mice were pre-treated with CoQ10 for a week, then ischemia was induced by common carotid artery ligation and following the reduction in inflammation [a week] the mice was treated with CoQ10. Nissl staining was applied for counting the necrotic cells of hippocampus and the western blot was performed to measure the Bax and Bcl2 expression. Cell death was significantly lower when mice were treated with CoQ10. Bax expression was significantly high in the ischemic group but low in the treatment group, and the bcl2 expression was lower in the ischemic group than the treatment and the vehicle groups. Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQI0 intake significantly reduced cell death and prevented the expression of Bax while inducing an increase in expression of bcl2

Effect of mozart husic on hippocampal content of BDNF in postnatal rats

Introduction: It has shown that listening to Mozart music can potentiate spatial tasks in human; and reduce seizure attacks in epileptic patients. A few studies have reported the effects of prenatal plus postpartum exposure of mice to the Mozart music on brain-drived neurotrophic factor [BDNF] in the hippocampus. Here we investigated the effect of postpartum exposure to The Mozart music on BDNF concentration in the hippocampus of rat. Methods: Thirty male one day old newborn Wistar rats divided randomly in two equal experimental and control groups. Experimental group exposed to slow rhythm Mozart music [Mozart Sonata for two pianos KV 448, 6 hour per day; sound pressure levels, between 80 and 100 dB] for 60 successive days. The control group was kept in separate room with housing conditions like experimental group except music exposure. After 60 days the rats were euthanized and hippocampuses extracted; then the content of BDNF protein was measured using ELISA sandwich method. Results: Data analysis revealed that rats exposed to Mozart Sonata music had significantly increased BDNF content in the hippocampus as compared to control rats [P +/- 0.01]. The concentrations of BDNF were 86.30 +/- 2.26 and 94.60 +/- 6.22 ng/g wet weight in control and music exposure groups respectively. Discussion: Exposure to the Mozart music early in life can increase the BDNF concentration in the hippocampus in rats

mitochondrial K-ATP channel opener, diazoxide, protects brain against ischemia-reperfusion injury in the rat

Even today there is no effective drug therapy to prevent neuronal loss after brain stroke. The objective of this research was to study effects of the mitochondrial K-ATP [MAK] channel regulators on neuronal cell population and neurological function after ischemia reperfusion in the rat. Rats were temporarily subjected to four vessels occlusion for 15 minutes followed by 24 hours reperfusion with or without MAK channel regulators. The normal cell count of neuronal population significantly increased in the K-ATP channel opener [diazoxide] treated ischemia-reperfusion group compared with the control group. Cell count and neurological function scores were dose dependent to MAK channel regulators in vivo. Our results showed that diazoxide treatment leads to better preservation of cortical neurons in rat