MDMA related neuro-inflammation and adenosine receptors.

3,4-methylenedioxymethamphetamine (MDMA) is a world-wide abused psychostimulant, which has the neurotoxic effects on dopaminergic and serotonergic neurons in both rodents and non-human primates. Adenosine acts as a neurotransmitter in the brain through the activation of four specific G-protein-coupled receptors and it acts as a neuromodulator of dopamine neurotransmission. Recent studies suggest that stimulation of adenosine receptors oppose many behavioral effects of methamphetamines. This review summarizes the specific cellular mechanisms involved in MDMA neuroinflammatory effects, along with the protective effects of adenosine receptors.

Protective impact of Rosa damascena against neural damage in a rat model of pentylenetetrazole (PTZ)-induced seizure.

OBJECTIVE: Based on the previously-declared anticonvulsant properties of Rosa damascena (R. damascena), this study explored the probable effects of R. damascena on neuronal apoptosis in the hippocampus of a rat model of pentylenetetrazole (PTZ)-induced seizure. MATERIALS AND METHODS: 40 male Wistar rats were randomely divided into control (n=8) and experimental (n=32) groups which underwent PTZ injection. A one-week pre-medication with 50 (PTZ-Ext 50) (n=8), 100 (PTZ-Ext 100) (n=8), and 200 (PTZ-Ext 200) (n=8) mg/kg of hydro-alcoholic extract of R . Damascene was performed while one experimental group (PTZ-induced group) (n=8) received only saline during the week before PTZ injection. After provocation of PTZ-induced seizures, the brains underwent tissue processing and TUNEL staining assay for apoptotic cell quantification. RESULTS: Our findings revealed that PTZ-induced seizures led to apoptosis in neuronal cells of all sub-regions of the hippocampus; yet, only at CA1, CA3 and DG sub-regions of the PTZ-induced group, the difference in the number of apoptotic neuronal cells was significant in comparison with the control group. In addition, pre-medication with the plant extract led to a significant drop in the quantity of apoptotic neurons in these sub-regions in comparison with the PTZ-induced group which received no pre-medication . CONCLUSION: The results of this study showed that R. damascena extract exerts neuro-protective effects on PTZ-induced seizure.

Vitamin C prevents hypothyroidism associated neuronal damage in the hippocampus of neonatal and juvenile rats: A stereological study.

Hypothyroidism causes an imbalance in antioxidant and pro-oxidants criteria in the brain and enhances the concentration of reactive oxygen species (ROS), and neuronal damage has been observed following an excessive ROS. The main purpose of this study was to examine the preventive effect of vitamin C on hypothyroidism associated neuronal damage in the hippocampus of neonatal and juvenile rats. Pregnant rats after delivery of their pups were randomly divided into four groups and treated with (1) normal drinking water as a control group, (2) Propylthiouracil (PTU) 0.005% added to drinking water, (3-, 4) PTU + Vit C 10 mg/ kg and PTU + Vit C 100 mg/ kg to drinking water. Treatment was carried out during rat's lactation period until to the postnatal day (PND) 60. To assess the histological and stereological changes that occur in this study, brains of 5 male pups were extracted. The number of dark neurons and apoptotic cells in the hippocampal sub-regions of PTU group was significantly greater than the control group's hippocampal sub-regions. In addition, hypothyroidism induced a reduction in the hippocampal volume and increased the numerical density and the total amount of dark neurons. The vitamin C only dose of 100 mg/kg significantly reduced the number of dark neurons and apoptotic cells (P < 0.01) and considerably weakened the influence of hypothyroidism on the volume reduction of the hippocampus (P < 0.05). The current study suggested that vitamin C administration has a possibility to prevent hippocampal neuronal damage caused by neonatal and juvenile hypothyroidism in rats.

Effects of MDMA (ecstasy) on apoptosis and heat shock protein (HSP70) expression in adult rat testis.

BACKGROUND: This study was conducted to investigate the effects of MDMA (3,4-methylenedioxymethamphetamine, ecstasy) on apoptosis and heat shock protein expression in adult rat testis. METHODS: Twenty male rats were divided into four groups, two experimental groups (1 and 2), sham control and control. For 16 consecutive days, the experimental groups 1 and 2 were received 5 and 10 mg/kg intraperitoneal (ip) injection of ecstasy, respectively, and in the sham control group, the only saline was injected. In the control group there was no intervention. Finally, the rat's testes were removed and processed for terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and immunohistochemical techniques. RESULTS: Both doses of MDMA in experimental groups 1 and 2 significantly increased the mean number of TUNEL-positive cells in the germinal epithelium and Leydig cells (p < 0.05). Also in the experimental groups, the immunoreactivity of heat shock protein 70 (HSP70) significantly increased in the testis (p < 0.05). CONCLUSIONS: The findings revealed that MDMA administration increases the level of immunoreactivity of HSP70 and TUNEL-positive cells in the testicular tissue.

Neuroprotective effects of Nigella sativa extract upon the hippocampus in PTU-induced hypothyroidism juvenile rats: A stereological study.

This study aimed to examine the neuroprotective effects of Nigella sativa (N. sativa) in the hippocampus of propylthiouracil (PTU)-induced hypothyroid rats during neonatal and juvenile growth. Twenty- five pregnant rats from early gestation (GD 0) were divided into five groups: (1) control (received drinking water), (2) PTU (received 0.005% PTU in drinking water), (3-5) PTU + NS 0.05%, PTU + NS 0.1%, PTU + NS 0.2% (along with PTU, received 0.05%, 0.1% and 0.2% W/V of N. sativa respectively) and treatment continued until postnatal day 60 (PN 60). The brains of male pups were removed for histological and stereological assessments. N. sativa extract significantly reduced the production of dark neurons and apoptotic cells in different areas of the hippocampus compared to the PTU group. Moreover, it significantly attenuated the effect of hypothyroidism on the volume reduction of the hippocampus. The results of the present study suggested that N. sativa extract has a potential ability to prevent the hippocampal neural damage after inducing hypothyroidism during neonatal and juvenile growth in rats.

Preventive effect of Coriandrum sativum on neuronal damages in pentylentetrazole-induced seizure in rats.

OBJECTIVE: Coriandrum sativum (C. sativum) as a medicinal plant has been pointed to have analgesic, hypnotic and anti-oxidant effects. In the current study, a possible preventive effect of the hydro-alcoholic extract of the plant on neuronal damages was examined in pentylenetetrazole (PTZ) rat model of seizure. MATERIALS AND METHODS: Forty male rats were divided into five main groups and treated by (1) saline, (2) PTZ: 100 mg/kg PTZ (i.p) and (3-5) 50, 100 and 200 mg/kg of hydro-alcoholic extract of C. sativum during seven consecutive days before PTZ injection. After electrocorticography (ECoG), the brains were removed to use for histological examination. RESULTS: All doses of the extract reduced duration, frequency and amplitude of the burst discharges while prolonged the latency of the seizure attacks (p<0.05, p<0.01, and p<0.001). Administration of all 3 doses of the extract significantly prevented from production of dark neurons (p<0.01, and p<0.001) and apoptotic cells (p<0.05, p<0.01, and p<0.001) in different areas of the hippocampus compared to PTZ group. CONCLUSION: The results of this study allow us to conclude that C. sativum, because of its antioxidant properties, prevents from neuronal damages in PTZ rat model of seizure.

The effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats.

Nigella sativa (NS) has been suggested to have neuroprotective and anti-seizures properties. The aim of current study was to investigate the effects of NS hydro-alcoholic extract on neural damage after pentylenetetrazole (PTZ) - induced repeated seizures. The rats were divided into five groups: (1) control (saline), (2) PTZ (50 mg/kg, i.p.), (3-5) PTZ-NS 100, PTZ-NS 200 and PTZ-NS 400 (100, 200 and 400 mg/kg of NS extract respectively, 30 min prior to each PTZ injection on 5 consecutive days). The passive avoidance (PA) test was done and the brains were then removed for histological measurements. The PTZ-NS 100, PTZ-NS 200 and PTZ-NS 400 groups had lower seizure scores than PTZ group (P < 0.01 and P < 0.001). The latency to enter the dark compartment by the animals of PTZ group was lower than control in PA test (P < 0.01). Pre-treatment by 400 mg/kg of the extract increased the latency to enter the dark compartment (P < 0.05). Meanwhile, different doses of the extract inhibited production of dark neurons in different regions of hippocampus (P < 0.001). The present study allows us to suggest that the NS possesses a potential ability to prevent hippocampal neural damage which is accompanied with improving effects on memory.

Anticonvulsant and neuroprotective effects of Rosa damascena hydro-alcoholic extract on rat hippocampus.

OBJECTIVE: Previously, analgesic, hypnotic, and anticonvulsant effects have been suggested for Rosa damascena (R. damascena). In the present study, possible anti-seizure and neuro-protective effects of hydro-alcoholic extract of R. damascena has been investigated after inducing seizures in rats by pentylenetetrazole (PTZ). MATERIALS AND METHODS: The rats were divided to five groups: (1) CONTROL: received saline, (2) PTZ: 100 mg/kg, i.p., (3) PTZ- Extract 50 mg/kg (PTZ-Ext 50), (4) PTZ- Extract 100 mg/kg (PTZ-Ext 100), and (5) PTZ- Extract 200 mg/kg (PTZ-Ext 200) groups which were treated with 50, 100, and 200 mg/kg respectively of hydro-alcoholic extract of R. dam ascena for one week before PTZ injection. The animals were examined for electrocorticography (ECoG) recording and finally, the brains were removed for histological study. RESULTS: The hydro-alcoholic extract of R. dam ascena significantly prolonged the latency of seizure attacks and reduced the frequency and amplitude of epileptiform burst discharges induced by PTZ injection. Moreover, all three doses of the extract significantly inhibited production of dark neurons in different regions of the hippocampus in the mentioned animal model. CONCLUSION: The present study showed that the hydro-alcoholic extract of R. dam ascena has anticonvulsant and neuroprotective effects. More investigations are needed to be done in order to better understand the responsible compound(s) as well as the possible mechanism(s).

The Effects of Nigella Sativa Hydro-alcoholic Extract on Memory and Brain Tissues Oxidative Damage after Repeated Seizures in Rats.

Regarding the therapeutic properties of Nigella sativa (NS), the effects of the plant hydro - alcoholic extract on learning, memory and brain tissues oxidative damage were investigated in penthylenetetrazole (PTZ) - induced repeated seizures. There were 4 experimental groups including: 1- control group; received saline, 2- PTZ group ; received saline and PTZ (50 mg/Kg, i.p) , 3-PTZ- NS 200 and 4- PTZ- NS 400 ; received 200 and 400 mg/Kg of NS extract respectively, before PTZ injection in 5 consecutive days. Seizure scores were lower in PTZ - NS 200 and 400, furthermore the seizure onset latencies were higher in these groups than PTZ group (P<0.05 and P<0.01 ). In Morris water maze, the time spent in target quadrant by PTZ group was lower than control group (P<0.05); while, 400 mg/Kg of the extract increased it (P<0.01). In the passive avoidance test, delay time to enter the dark by PTZ group was lower than control at 1 and 24 hours after training (P<0.01- P<0.001); while, 400 mg/Kg of the extract increased it (P<0.05). The total thiol concentration in hippocampal and cortical tissues of PTZ group was reduced while, MDA concentration was higher than control (p<0.05 - p<0.001). Administration of the extract increased the total thiol and decreased the MDA concentrations (p<0.01- p<0.001). It is concluded that the hydro-alcoholic extract of NS possess beneficial effects on learning and memory impairments in repeated seizures model which is accompanied by antioxidant effects in the brain.

Neuronal cell reconstruction with umbilical cord blood cells in the brain hypoxia-ischemia.

BACKGROUND: Brain hypoxia-ischemia is a human neonatal injury that is considered a candidate for stem cell therapy. METHODS: The possible therapeutic potential of human umbilical cord blood (HUCB) stem cells was evaluated in 14-day-old rats subjected to the right common carotid occlusion, a model of neonatal brain hypoxia-ischemia. Seven days after hypoxia-ischemia, rats received either saline solution or 4 × 105 HUCB cells i.v. Rats in control group did not receive any injection. After two weeks, rats were assessed using two motor tests. Subsequently, rats were scarified for histological and immunohistochemical analyses. RESULTS: Our immunohistochemical findings demonstrated selective migration of the injected HUCB cells to the ischemic area as well as reduction in infarct volume. Seven days after surgery, we found significant recovery in the behavioral performance in the test group (12.7 +/- 0.3) compared to the sham group (10.0 +/-0.05), a trend which continued to day 14 (15.3 ± 0.3 vs. 11.9 ± 0.5, P<0.05). Postural and motor asymmetries at days 7 and 14 in the test group showed a significant decrease in the percentage of right turns in comparison to the sham group (75% and 59% vs. 97% and 96%, P<0.05). CONCLUSION: The results show the potential of HUCB stem cells in reduction of neurologic deficits associated with neonatal hypoxia-ischemia.

Intravenous administration of human umbilical cord blood-mononuclear cells dose-dependently relieve neurologic deficits in rat intracerebral hemorrhage model.

Human umbilical cord blood (HUCB) is now considered as a valuable source for stem cell-based therapies. Previous studies showed that intravascular injection of the HUCB significantly improves neurological functional recovery in a model of intracerebral hemorrhage (ICH). To extend these findings, we examined the behavioral recovery and injured volume in the presence of increasing doses of human umbilical cord blood derived mononuclear cells (HUC-MCs) after intracerebral hemorrhage in rats. The experimental ICH was induced by intrastriatal administration of bacterial collagenase IV in adult rats. One day after the surgery, the rats were randomly divided into 4 groups to receive intravenously either BrdU positive human UC-MCs (4 × 10(6), 8 × 10(6) and 16 × 10(6) cells in 1 ml saline, n=10, respectively) as treated groups or the same amount of saline as lesion group (n=10). There was also one group (control n=10) that received only the vehicle solution of collagenase. The animals were evaluated for 14 days with modified limb placing and corner turn tests. The transplanted human UC-MCs were also detected by immunohistochemistry with labeling of BrdU. Two weeks after infusion, there was a significant recovery in the behavioral performance when 4 × 10(6) or more UC-MCs were delivered (P<0.05-0.001). Injured volume measurements disclosed an inverse relationship between UC-MCs dose and damage reaching significance at the higher UC-MCs doses. Moreover, human UC-MCs were localized by immunohistochemistry only in the injured area. Intravenously transplanted UC-MCs can accelerate the neurological function recovery of ICH rat and diminish the striatum lesion size by demonstrating a dose relationship between them.

Therapeutic benefit of intravenous administration of human umbilical cord blood- mononuclear cells following intracerebral hemorrhage in rat.

OBJECTIVES: Human umbilical cord blood (HUCB) is now considered as a valuable source for stem cell-based therapies. Previous studies showed that intravascular injection of the HUCB significantly improves neurological functional recovery in a rat model of intracerebral hemorrhage (ICH). In the present study, we hypothesize transplanted HUCB derived mononuclear cells (UC-MCs) can decrease injured volume and also ameliorate neurological function in ICH rats. MATERIALS AND METHODS: Experimental ICH was induced by intrastriatal administration of collagenase in rats. One day after surgery, the rats were divided into 3 groups to receive intravenously either BrdU positive human UC-MCs [(4×10(6) and 8×10(6) cells in 1 ml saline, n=10 respectively) as treated groups] or the same amount of saline [as lesion group (n=10)]. There was also one group (control) that received only vehicle solution of collagenase. The animals were evaluated for 14 days with behavioral tests. Transplanted UC-MCs were detected by immunohistochemistry. Histological data and scores of functional tests were analyzed using ANOVA. Cellular co-localization of BrdU+ cells in the histological slides was determined by software Image J. RESULTS: Intravenously transplanted UC-MCs migrated selectively to the hematomal area and reduce injured volume. The UC-MCs transplanted groups showed better performance on functional tests after 2 weeks compared with the lesion and control groups (P< 0.05). There was no difference in the functional recovery and injured volume improvement between the 2 treated groups. CONCLUSION: Intravenously transplanted UC-MCs accelerate neurological function recovery of ICH rat and diminish the striatum lesion size. Thus these cells may provide a potential cell candidate for cell-based therapy in ICH.