Effect of Adenosine Receptor Agonist and Ascorbic Acid on Ultrastructure of Hippocampal CA1 Neurons after Ischemia-Reperfusion Injury

Background: In brain ischemia, blood and oxygen supply decrease and after reperfusion, free radicals and reactive oxygen species (ROS) cause severe damage. As hippocampal injury after ischemia-reperfusion causes some complications, in this study we analyzed the effect of adenosine receptor agonist (N6-cyclopentyladenosine or CPA) and ascorbic acid on ultrastructure of hippocampal CA1 neurons after ischemia-reperfusion. Methods: 35 male rats in 5 groups were used. Ischemia-reperfusion performed by occlusion of common carotids for 15 minutes. CPA and ascorbic acids were intraperitoneally injected for 7 days after ischemia, and 2 weeks before and for 7 days after ischemia, respectively. After 20 days, brain samples were isolated, prepared, and assayed using transmission electron microscopy (TEM). Findings: Ultrastructure assay of hippocampal CA1 neurons after ischemia-reperfusion with transmission electron microscopy showed recovery of intracellular organelles particularly mitochondria of treated groups. In combination therapy, these improvements were better. Conclusion: Intraperitoneal injection of CPA and ascorbic acid after ischemia-reperfusion can reduce neural damage in CA1 region of hippocampu

The Role of The A2A Receptor in Cell Apoptosis Caused by MDMA

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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

Introduction: Preliminary studies have con.rmed reduction in cell death following treatment with antioxidants. According to this .nding 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. Methods: We studied the protective role of CoQ10 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 in.ammation (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.Results: Cell death was signi.cantly lower when mice were treated with CoQ10. Bax expression was signi.cantly 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.Discussion: Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQ10 intake signi.cantly reduced cell death and prevented the expression of Bax while inducing an increase in expression of bcl2

The Effect of Aqueous Extract of Fennel (Foeniculum Vulgare) on Kidney in BALB/C Adult Male Mic

Background & Objective: Fennel as a medicinal plant has a long history of use in traditional herbal medicine. But there have been few reports of this drug toxicity in different tissues. In this study, the effect of aqueous extract of fennel on the kidneys of adult male BALB/C mice and renal blood factors was investigated. Materials & Methods: In this study, 40 adult male BALB/C mice in the range of 20-22 g were used. Mice were divided into 5 groups. Group 1: Control, Group 2: Sham, that received normal saline intraperitoneal (IP) for 14 days. Experimental groups received doses of 50, 100 and 200 mg/kg of body weight of the aqueous extract of fennel IP for 14 days. After 14 days of treatment, the mice were anesthetized and after blood sampling from the heart, their kidneys were removed for pathology examination. Histological sections were prepared and stained with H & E and investigated by the optical microscope. Data were analyzed using SPSS software. Result: The mean number of glomeruli, cortex thickness, vascular occlusion, leukocyte infiltration and other histologic indices in the group received 200 mg/kg of an aqueous extract of fennel had a significant difference with control group. However, weight, BUN, creatinine and medulla thickness indices did not have any significant difference with the control group. Conclusion: The results showed that aqueous extract of fennel at doses of 50 and 100 mg/kg had no toxic effects on parenchyma and renal cells, but dose of 200 mg/kg had toxic effects on the kidney

The Mediating Role of A2A Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat

Introduction: The 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug and a major source of substance abuse, which ultimately leads to sensations of well-being, elation and euphoria, moderate derealization/depersonalization, and cognitive disruptions, as well as intense sensory awareness. The mechanisms involved in memory impairment induced by MDMA are not completely understood.&nbsp; Methods: The current study used 40 Sprague-Dawley rats, weighted 200 to 250 g. Experiments were performed in four groups, each containing 10 rats. The first group of rats was used as the control, treated with dimethyl sulfoxide (DMSO). The second group was treated with MDMA. The third group was treated with MDMA and CGS (the adenosine A2A receptor agonist, 2-[p-(2- carboxyethyl) phenethylamino]-5&prime;-N-ethylcarboxamidoadenosine) (CGS 21680) and the fourth group was treated with MDMA and SCH (the A2A receptor antagonist [7-(2-phenylethyl)-5-amino-2-(2-furyl-) pyrazolo-[4, 3-e]-1, 2, 4 triazolo [1,5-] pyrimidine]) (SCH 58261). The drugs in all groups were administrated intraperitoneally (i.p.) once a day for 7 days. In 5 rats of each group, following perfusion, samples were taken from hippocampi to investigate apoptosis. Accordingly, the samples were stained using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay kit, and studied by light microscopy. In other rats, fresh tissue was also removed to study the expression of bax and bcl-2 by Western blotting technique.&nbsp; Results: It was observed that the coadministration of MDMA with CGS reduced bax expression and prevented apoptosis of hippocampal cells. The coadministration of MDMA and SCH increased bax expression, and also increased the frequency of hippocampal cell apoptosis. Conclusion: The results of the current study showed that administration of CGS with MDMA decreased the common side effects associated with MDMA

The Effect of Diazoxide on Ultrastructural Changes Following Ischemia-Reperfusion Injury of Rat Brain

A B S T R A C T Introduction: Even today there is no effective drug therapy to prevent neuronal loss after brain stroke. In the present study we studied the effect of mitochondrial KATP channel regulators on neuronal ultrastructure after ischemia reperfusion in the rat. Materials & Methods: Rats temporarily subjected to four vessels occlusion for 15 minutes followed by 24 hours reperfusion with or without K-ATP channel regulators. Results: Neuronal ultrastructure significantly improved in K-ATP channel opener (diazoxide) treated ischemia-reperfusion group compared with control group. Discussion: Our results showed that dizoxide treatment after ischemia reperfusion leads to better preservation of cortical neurons in rat

The Effect of Diazoxide on Ultrastructural Changes Following Ischemia-Reperfusion Injury of Rat Brain

A B S T R A C T Introduction: Even today there is no effective drug therapy to prevent neuronal loss after brain stroke. In the present study we studied the effect of mitochondrial KATP channel regulators on neuronal ultrastructure after ischemia reperfusion in the rat. Materials &amp; Methods: Rats temporarily subjected to four vessels occlusion for 15 minutes followed by 24 hours reperfusion with or without K-ATP channel regulators. Results: Neuronal ultrastructure significantly improved in K-ATP channel opener (diazoxide) treated ischemia-reperfusion group compared with control group. Discussion: Our results showed that dizoxide treatment after ischemia reperfusion leads to better preservation of cortical neurons in rat

Brain Derived Neurotrophic Factor Modification of Epileptiform Burst Discharges in a Temporal Lobe Epilepsy Model

Introduction: Transforming Growth Factor-Beta 1 (TGF-&beta;1) is a pleiotropic cytokine with&nbsp;potent anti-inflammatory property, which has been considered as an essential risk factor in the&nbsp;inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression&nbsp;of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-&beta;1 gene polymorphism&nbsp;has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide&nbsp;a relatively comprehensive account of the relation between -509C/T gene polymorphisms of&nbsp;TGF-&beta;1 and susceptibility to IS. Methods: Male Wistar rats were divided into sham (receiving phosphate buffered saline within&nbsp;dorsal hippocampus), pilocarpine (epileptic model of TLE), single injection BDNF (epileptic rats&nbsp;which received single high dose of BDBF within dorsal hippocampus), and multiple injections&nbsp;BDNF (epileptic rats which received BDNF in days 10, 11, 12, and 13 after induction of TLE)&nbsp;groups. Their electrocorticogram was recorded and amplitude, frequency, and duration of spikes&nbsp;were evaluated. Results: Amplitude and frequency of epileptiform burst discharges were significantly decreased&nbsp;in animals treated with BDNF compared to pilocarpine group. Conclusion: Our findings suggested that BDNF may modulate the epileptic activity in the&nbsp;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

Evaluation of the neuroprotective effects of electromagnetic fields and coenzyme Q 10 on hippocampal injury in mouse

Electromagnetic fields (EMFs) are reported to interfere with chemical reactions involving free radical production. Coenzyme Q(10) (CoQ10) is a strong antioxidant with some neuroprotective activities. The purpose of this study was to examine and compare the neuroprotective effects of EMF and CoQ10 in a mouse model of hippocampal injury. Hippocampal injury was induced in mature female mice (25-30g), using an intraperitoneal injection of trimethyltin hydroxide (TMT; 2.5mg/kg). The experimental groups were exposed to EMF at a frequency of 50Hz and intensity of 5.9mT for 7hr daily over 1 week or treated with CoQ10 (10mg/kg) for 2 weeks following TMT injection. A Morris water maze apparatus was used to assess learning and spatial memory. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests were also performed for the histopathological analysis of the hippocampus. Antiapoptotic genes were studied, using the Western blot technique. The water maze test showed memory improvement following treatment with CoQ10 and coadministration of CoQ10+EMF. The Nissl staining and TUNEL tests indicated a decline in necrotic and apoptotic cell count following treatment with CoQ10 and coadministration of CoQ10+EMF. The Western blot study indicated the upregulation of antiapoptotic genes in treatment with CoQ10, as well as coadministration. Also, treatment with EMF had no significant effects on reducing damage induced by TMT in the hippocampus. According to the results, EMF had no significant neuroprotective effects in comparison with CoQ10 on hippocampal injury in mice. Nevertheless, coadministration of EMF and CoQ10 could improve the neuroprotective effects of CoQ10

Evaluation of the neuroprotective effects of electromagnetic fields and coenzyme Q10 on hippocampal injury in mouse

Electromagnetic fields (EMFs) are reported to interfere with chemical reactions involving free radical production. Coenzyme Q10 (CoQ10) is a strong antioxidant with some neuroprotective activities. The purpose of this study was to examine and compare the neuroprotective effects of EMF and CoQ10 in a mouse model of hippocampal injury. Hippocampal injury was induced in mature female mice (25–30 g), using an intraperitoneal injection of trimethyltin hydroxide (TMT; 2.5 mg/kg). The experimental groups were exposed to EMF at a frequency of 50 Hz and intensity of 5.9 mT for 7 hr daily over 1 week or treated with CoQ10 (10 mg/kg) for 2 weeks following TMT injection. A Morris water maze apparatus was used to assess learning and spatial memory. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests were also performed for the histopathological analysis of the hippocampus. Antiapoptotic genes were studied, using the Western blot technique. The water maze test showed memory improvement following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Nissl staining and TUNEL tests indicated a decline in necrotic and apoptotic cell count following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Western blot study indicated the upregulation of antiapoptotic genes in treatment with CoQ10, as well as coadministration. Also, treatment with EMF had no significant effects on reducing damage induced by TMT in the hippocampus. According to the results, EMF had no significant neuroprotective effects in comparison with CoQ10 on hippocampal injury in mice. Nevertheless, coadministration of EMF and CoQ10 could improve the neuroprotective effects of CoQ10. keywords:CoQ10 electromagnetic fields (EMFs) neuroprotective effect trimethyltin hydroxide (TMT