Background: Ischemia reperfusion injury following acute ischemic insult is responsible for extension of injury.Bosentan is an endothelin receptor antagonist, which is currently used as a strong vasoconstrictor. This study aims to investigate the effects of bosentan on ischemia reperfusion injury after brain ischemic stroke in rat model. Methods: Forty male Wistar rats were randomly allocated into four study groups: Sham group: Rats underwent the anesthesia & surgery for an identical period to the other 3 study groups without intervention. Control group: Rats underwent anesthesia & surgery including bilateral common carotid artery ligation (BCCAL) for 30 minutes and then reperfusion for 1 hour. Vehicle group: Four days before ischemia, rats were administered with a vehicle (5% gummi arabicum) and then anesthesia &BCCAL surgery were performed. Bosentan treat group: Four days before Al-Aubaidy et al (2019): Bosentan effect in brain ischemia September 2019 Vol. 22(IV) ©Annals of Tropical Medicine & Public Health SPe145ischemia, rats were administered with bosentan (100mg/ kg/day) and then anesthesia & BCCAL surgery were performed.Results: Bosentan treated group exhibited lower concentration of interleukin 6 (IL-6)in the brain (2168.0±30.67 pg/mL) than in the control group (2571.37±96.58 pg/mL) (P≤0.05). In addition, interleukin 10 (IL-10) levels were significantly high in the bosentan group (275.7±15.97 pg/mL) when compared to the control group (244.05±12.23 pg/mL) (P≤0.05). This was associated with a non-significant reduction in the brain levels of endothelia nitric oxide synthase (eNOS) in the bosentan treated groups (90.23±1.14 ng/mL) when compared to the control group (90.94±2.48), (P>0.05). Conclusion:Bosentan treatment have protective effects against the inflammatory damage following ischemia reperfusion injury following acute myocardial infarction.

This study was performed to evaluate the neuroprotective effect of Azelnidipine in cerebral ischemia/reperfusion and to envisage its mechanisms. Twenty-eight adult male Sprague-Dawley rats weighing 200–300 g were randomized into 4 groups (7 rats in each group). Sham (neck dissection without bilateral common carotid artery occlusion), control (30 minutes of bilateral common carotid artery occlusion and reperfusion for 1 hour), vehicle (identical volume of 0.3% carboxymethylcellulose (CMC) orally every day then bilateral common artery occlusion and reperfusion), and Azelnipine-treated rats (7 days of Azelnidipine pretreatment 3 mg/kg/day followed by bilateral common carotid artery occlusion and reperfusion). In addition to brain infarct volume and histopathological assessment, the brain tissues were harvested to evaluate cerebral IL-6, IL-10, TNF-α, ICAM-1, NF-κB p65, and total antioxidant capacity levels. Cerebral levels of IL-6, IL-10, TNF-α, NF-κB p65, and ICAM-1, besides cerebral infarct volume, were significantly elevated in control and vehicle related to sham groups, while total antioxidant capacity was markedly reduced. Azelnidipine treatment resulted in remarkable upregulation of total antioxidant capacity; meanwhile, IL-6, TNF-α, NF-κB p65, and ICAM-1 showed a considerable reduction. Cerebral IL-10 levels were not affected by Azelnidipine pretreatment. Histologically, control and vehicle rats showed severe ischemic injury, which was greatly reversed by Azelnidipine treatment. The current study disclosed that Azelnidipine could markedly reduce cerebral infarct volume and ameliorate histopathological damage in male rats exposed to cerebral ischemia/reperfusion. The neuroprotective effects of Azelnidipine probably stemmed from its anti-inflammatory and antioxidative properties. Azelnidipine had no effect on cerebral IL-10 levels.

The aim: To see whether nimodipine had neuroprotective effects in cerebral ischemia/reperfusion injury. Materials and methods: A total of 28 adult male Sprauge-dawley rats weighting 200-300 g were distributed randomly into 4 groups (7 animals in each group): sham (neck dissection without bilateral common carotid artery occlusion), control (bilateral common carotid artery occlusion for 30 minutes and reperfusion for 1 hour), vehicle (7 days of daily carboxymethylcellulose by oral gavage followed by bilateral carotid artery occlusion and reperfusion), and nimodipine-treated rats (7 days of 3 mg/kg/day of oral Azelnidipine pretreatment then bilateral common carotid artery occlusion and reperfusion). Besides assessment of histological changes and brain infarct volume, the brain tissues were sectioned to estimate NF-κB p65, IL-6, IL-10, TNF-α, ICAM-1 and total anti-oxidant capacity. Results: Cerebral NF-κB p65, IL-6, IL-10, TNF-α, ICAM-1, in addition to cerebral infarct size were markedly increased in control and vehicle related to sham rats, while total anti-oxidant capacity was considerably decreased. Treatment with nimodipine resulted in remarkable increment of total anti-oxidant capacity, while NF-κB p65, IL-6, TNF-α, and ICAM-1 showed great reduction. Cerebral IL-10 levels didn’t change by nimodipine treatment. Histologically, control and vehicle rats showed severe brain ischemic changes which is dramatically reduced by nimodipine treatment. Conclusions: Our study results revealed that nimodipine can greatly decrease cerebral infarct size and reduce histological ischemic injury in male rats subjected to cerebral ischemia/ reperfusion. The neuroprotective actions of nimodipine possibly originated from its anti-inflammatory and antioxidative effects. Nimodipine protection was unrelated to IL-10.

Background and objective: Magnesium sulfate has neuroprotective effects and decrease overall neuronal firing. It is also decrease firing of excitable tissues outside the brain. It is not known whether this neuroprotective effect is due to antioxidant effect, anti-inflammatory or other mechanism. In this research we study the anti-inflammatory effect of magnesium sulfate in rat brain following  ischemia reperfusion stress.Material and methods: Twenty four rats were grouped into 4 groups: The first (sham group), the second (control) and the third group(control-vehicle) and the forth  (treated with Magnesium sulfate). Animals in the second group underwent bilateral common carotid artery ligation without treatment, whereas the forth group were injected with magnesium sulfate 250mg/kg intraperitoneally before procedure. Blood samples were taken after the procedure for measurement of serum level of IL-9, MCP-1 and ICAM.Results: Serum level of IL-9 in control group was 163.3 ± 30.4 pg/mL and it significantly decreased in magnesium sulfate treated group (21.8 ± 1.72 pg/mL). serum level of MCP-1 in the control group was 109.05 ± 18.2 pg/mL while  it significantly reduced in magnesium sulfate treated group (38.16 ± 3.54 pg/mL). mean serum levels of ICAM of control was 362.8 ± 26.81 pg/mL while mean serum level of ICAM in treated group was 35.5 ± 4.71 pg/mL.Conclusion: magnesium sulfate significantly decreases the inflammatory markers IL-9, MCP-1 and ICAM in global ischemia model in rats.