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

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

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

Role of fibrocytes [CD34+] derived from peripheral blood in the pathology of dermal fibrosis in a model of scleroderma

Peripheral blood fibrocytes are a newly identified circulating leukocyte subpopulation that migrates into injured tissue where it may display fibroblast-like properties and participate in wound healing and fibrosis of skin and other organs. In this study, fibrocyte recruitment to skin in a bleomycin-induced dermal fibrosis model of human scleroderma in vivo was studied. Sections of skin from normal mice [control group] and bleomycin-treated C57BL/6 mice [Experimental group] were stained for Procollagen a2 Type I and CD34 and the double stained cells, and also fibrocytes were counted in the tissue sections. There were more fibrocytes in the dermis of experimental group than control group. There was no significant difference in fibrocyte number between skin samples with 1 week bleomycin treated and 3 weeks treated samples. We also found that fibrocytes [CD34+ and procollagen+] were mainly localized in clusters around blood vessels in the dermis and also individually close to epithelium. Our data suggest an important role of fibrocytes in the pathology of dermal fibrosis

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