Background & objectives: Stroke remains one of main causes of death and disability in human. Animal models of the brain ischemia provide an important roles for studying of the pathophysiological mechanisms and evaluating of the efficacy of neuroprotective agents. The aim of this study is introducing a new model of the focal cerebral ischemia with increased success and low mortality rate.

 Methods: Fifteen six male mice were anesthetized with isofolorane and mixture of O2/N2O divided in four groups. Focal cerebral ischemia was induced by intraluminal filament method. A silicon coated nylon filament was used for middle cerebral artery occlusion. Regional cerebral blood flow was monitored by laser Doppler flowmetery for leading of filament in vascular pathway. In the 24 hours following ischemia (60minutes), animals were assessed for neurological outcome, infarct volume and brain edema induction. A new and reformed neurological test was used for evaluation of neurological deficits. 10 µm coronal sections were collected from 12 levels of the brain and stained, digitized and quantified by using an image analysis system. Ischemic brain edema was investigated by brain water content detection.

 Results: When sham operated mice had no motor deficit and infarction, induction of ischemia in ischemic group, seriously caused impairment of motor functions (neurological deficit score 3.36±0.25). Mean total infarct volume of left (ischemic) hemisphere was 85.2±4.9 mm³ and 47 percent of infarction occurred in subcortical regions of the brain. Induction of focal cerebral ischemia in the left (ischemic) hemisphere of the brain significantly increased water content (83.1±0.29 percent) compared to both hemispheres of sham group and right hemisphere of the same group. Success rate of ischemia induction was 97.6 percent and mortality rate was 4.21 percent.

 Conclusion: These findings indicate. This present model can be used for brain ischemia studies with high success rate, low mortality rate and narrow variety of the size and location of infarct volume. This model provides controlled and standard conditions to study ischemic brain injury and edema formation and introduce new therapeutic strategies.

 Background & objectives: Ischemic brain edema is one of the most important complications of cerebral infarction. Edema aggravates the primary ischemic injury to the brain. It was demonstrated that the renin-angiotensin system (RAS) and its active peptide angiotensin II involved in ischemic brain injury. But role of RAS in the formation of ischemic edema is not clear. The present study was conducted to investigate the effects of the RAS inhibition by enalapril on edema formation and blood-brain barrier (BBB) disruption.

 Methods: In this research frothy Sprague Dawley male rat in six groups were studied. Animals were anesthetized with chloral hydrate (400mg/kg, IP). Transient focal cerebral ischemia was induced by occlusion of right middle cerebral artery using intraluminal filament method. Three groups of animals as sham, ischemic and enalapril receiving (0.03mg/kg) groups were studied for assessment of neurological outcome and brain edema formation. 24 hours following ischemia (60minutes), animals were assessed for neurological deficits. Ischemic brain edema was investigated by brain water content detection. Another three groups of animals at the same conditions were studied to evaluate the possible disruption of BBB by Evans blue extravasation technique.

 Results: When sham operated rats had no motor deficit, induction of ischemia in ischemic group, seriously caused impairment of motor functions and neurological deficit score(NDS) of ischemic group was 2.67±0.42. Pretreatment with enalapril (0.03mg/kg) significantly reduced NDS and improved motor dysfunctions (1.5±0.34, P<0.05). Induction of ischemia seriously caused edema formation in right (ischemic) hemisphere of the brain in ischemic group (4.1±0.4 percent). Pretreatment with enalapril (0.03mg/kg) significantly decreased edema compared to ischemic group (1.89±0.23 percent). Extravasation of Evans blue in right side of the brain in ischemic group (12.48±1.94 μg/g) was significantly more than sham group. Pretreatment with enalapril (0.03mg/kg) had protective effects on BBB function and decreased Evans blue extravasation by 44.5 percent (6.92±1.46 μg/g).

 Conclusion: RAS�inhibition by enalapril reduces ischemic brain edema formation by protecting the integrity of BBB and reducing its permeability following focal cerebral ischemia in rat. Pre-ischemic inhibition of RAS activity may reduce ischemic brain injury by ameliorating edema formation.

  Background & objectives: Ischemic stroke is the third leading cause of death and disability in most of the human societies. There is no effective treatment due to complexity of the pathophysiological mechanisms. Today, more researches are designed to introduce involving factors and new treatment strategies in brain ischemia. The objective of this study is to introduce an experimental model of the focal cerebral ischemia in rat with increased success rate and low mortality rate.

  Methods: In this research 32 male rats (Sprague-Dawley) were studied as in four experimental groups. Animals were anesthetized with chloral hydrate (400mg/kg, ip). Focal cerebral ischemia was induced by intraluminal filament method. A silicon coated nylon filament was used for middle cerebral artery occlusion. Regional cerebral blood flow was monitored by laser Doppler flowmetery to guide the insertion of the filament into the vascular pathway. 24 hours after ischemia (90minutes), animals were assessed for neurological outcome, infarct volume and brain edema formation. A new and reformed neurological test was used for evaluation of neurological deficits. 2 - millimeter coronal sections were collected from 6 levels of the brain and stained, digitized and quantified by using an image analysis system. Ischemic brain edema formation was investigated by brain water content detection.

  Results: Induction of ischemia in ischemic group, seriously caused impairment of motor functions (neurological deficit score 4±0.5) While sham operated rats had no motor deficit and infarction. Mean total infarct volume of left (ischemic) hemisphere was 402±43 mm³ and 62.7 percent of infarction occurred in cortical regions of the brain. Induction of focal cerebral ischemia in the left (ischemic) hemisphere of the brain significantly increased water content (84±0.23 percent) compared to both hemispheres of sham group and right hemisphere of the same group. Success rate of ischemia induction was 100 percent and there was no mortality due to technical problems.

  Conclusion: Our findings indicate that continuous recording of regional cerebral blood flow using laser Doppler flowmeter had significant role in increasing success rate and lowering mortality rate in the present model of ischemic rat. This experimental model with high success rate and low limitation can be used for brain ischemia studies and evaluating new therapeutic strategies.

Background & objectives: Stroke is third leading cause of death and disability in the most of human communities. The use of herbs and medicinal plants in different countries is increasing. Today, herbal medicine is used as alternative or complementary therapies with a fewer side effects. Nigella sativa has a rich medical and religious history. Oxidative stress has important role in the pathophysiology of stroke. As Nigella sativa has antioxidant effects, its administration may produce a protective effect against complications of this disease. We examined the effects of the treatment with Nigella sativa oil on the cerebral infarction and edema.

Methods: 48 Male Sprague-Dawley rats were divided into three groups, sham, control ischemic and Nigella sativa oil treated (2 ml/kg) ischemic groups. Transient focal cerebral ischemia was induced by 90-min-long occlusion of the left middle cerebral artery followed by 24-h-long reperfusion. Neurological deficit score was evaluated at the end of the reperfusion period. Thereafter, the animals were randomly selected and used for two projects: (i) Measurement of the infarct volumes and neurological outcome (ii) investigation of ischemic brain edema formation using a wet/dry method.

Results: Induction of cerebral ischemia in the control group produced considerable brain infarction in conjunction with impaired motor functions and severely brain edema. Treatment with Nigella sativa oil significantly reduced the infarct volume and improved the motor functions. The water content in the left (lesioned) hemisphere was considerably elevated in the control ischemic group. Administration of the Nigella sativa oil significantly lowered the water content in the ischemic lesioned hemisphere.

Conclusion: Treatment with Nigella sativa oil can noticeably decrease the ischemic brain injury, attenuate edema formation and improve motor disabilities.

Background & objectives: Stroke is third leading cause of death and disability in the most of human communities. Several experimental studies have shown that combination therapy with drugs that act via different mechanisms can produce amplified protective effects. We examined the effects of combination therapy with candesartan and alpha tocopherol against cerebral ischemia.

Methods: Male Sprague-Dawley rats were divided into five groups (n=24): sham, control ischemic, candesartan treated (0.3 mg/kg), alpha tocopherol treated (30 mg/kg) and combined treated ischemic groups. Transient focal cerebral ischemia was induced by 90-min-long occlusion of the left middle cerebral artery followed by 24-h-long reperfusion. Neurological deficit score was evaluated at the end of the reperfusion period. Thereafter, the animals were randomly used for measurement of the infarct volumes and investigation of ischemic brain edema formation using a wet/dry method.

Results: Induction of cerebral ischemia produced considerable brain infarction in conjunction with severely impaired motor functions and edema formation. Combined treatment with candesartan and alpha tocopherol significantly reduced the infarct volume and lowered the water content in the ischemic lesioned hemisphere. These effects on brain edema and oxidative stress biomarkers were significantly more than the monotherapy with candesartan.

Conclusion: The combination therapy with candesartan and alpha tocopherol can noticeably decrease ischemic brain injury and attenuate edema formation likely via increasing the antioxidant activity.