BACKGROUND:Previous studies have demonstrated that homocysteine is an independent risk factor for ischemic stroke,as determined by detection of apoptosis and oxygen-free radical scavengers following cerebral ischemia.However,the mechanisms of homocysteine remain unclear.Several reports have addressed the effects of homocysteine on ischemic stroke.OBJECTIVE:To analyze the effects of homocysteine on apoptosis,intracellular superoxide dismutase(SOD) activity,and malondialdehyde content in tissue surrounding hematoma in rats with cerebral hemorrhage,and to determine the action pathway of malondialdehyde following cerebral hemorrhage.DESIGN,TIME AND SETTING:The randomized,controlled,animal experiment was performed at the Laboratory of Molecular Biology,Hospital Affiliated to Luzhou Medical College,China from April 2007 to April 2008.MATERIALS:In situ apoptosis detection kit(Roche,Mannheim,Germany),SOD detection kit and malondialdehyde detection kit(Nanjing Jiancheng Bioengineering Institute,China),and homocysteine(Sigma,St Louis,MO,USA) were used in the present study.METHODS:A total of 75 Sprague Dawley rats were equally and randomly assigned to sham surgery,model,and homocysteine groups.Autologous blood was infused into the caudate putamen of rats to establish models of cerebral hemorrhage in model and homocysteine groups.Homocysteine was injected directly into the brain through the skull at the hematoma hemisphere at 30 minutes after model induction in the homocysteine group.MAIN OUTCOME MEASURES:At 6,12,24,and 72 hours,as well as 1 week,post-surgery,neurological deficits were observed in each group.Brain water content was measured using the dry-wet weight method.Cell apoptosis in tissue surrounding the hematoma was detected utilizing terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL).SOD activity and malondialdehyde content in tissue surrounding the hematoma were respectively measured using the xanthine oxidase and thiobarbituric acid methods.RESULTS:Neurological function was similar between model and homocysteine groups following cerebral hemorrhage(P > 0.05).Brain water content was increased at 12 hours post-surgery,peaked at 3 days,and remained unchanged at 7 days in the model group.Brain edema was not significantly aggravated following homocysteine intervention(P > 0.05),but SOD activity significantly decreased and malondialdehyde content significantly increased(P < 0.05).The number of apoptotic cells increased in rats with cerebral hemorrhage at 12 hours(P < 0.05),and numbers peaked at 72 hours following model establishment(P < 0.05).The time of peak value was identical between model and homocysteine groups.Brain water content was negatively associated with SOD activity(rmodel group =-0.448,P < 0.05;rhomocysteine group =-0.612,P < 0.05),but was positively associated with malondialdehyde content(rmodel group = 0.542,P < 0.05;rhomocysteine group = 0.684,P < 0.05) in brain tissues surrounding the hematoma following surgery in model and homocysteine groups.CONCLUSION:Homocysteine aggravates neurological dysfunction and brain edema in rats with cerebral hemorrhage.The mechanisms of action are likely associated with production of oxygen-free radical and cellular apoptosis following cerebral hemorrhage. BACKGROUND: Previous studies have demonstrated that homocysteine ​​is an independent risk factor for ischemic stroke, as determined by detection of apoptosis and oxygen-free radical scavengers following cerebral ischemia. However, the mechanisms of homocysteine ​​remain unclear. Past reports have addressed the effects of homocysteine on ischemic stroke. OBJECTIVE: To analyze the effects of homocysteine ​​on apoptosis, and intracellular superoxide dismutase (SOD) activity, and malondialdehyde content in tissue surrounding hematoma in rats with cerebral hemorrhage, and to determine the action pathway of malondialdehyde following cerebral hemorrhage. TIME AND SETTING: The randomized, controlled, animal experiment was performed at the Laboratory of Molecular Biology, Hospital Affiliated to Luzhou Medical College, China from April 2007 to April 2008. MIALIALS: In situ apoptosis detection kit (Roche, Mannheim, Germany), SOD detection kit and malondialdehyde detection kit (Nanjing Jiancheng Bioengineering Institute , China), and homocysteine ​​(Sigma, St Louis, MO, USA) were used in the present study. METHODS: A total of 75 Sprague Dawley rats were equally and randomly assigned to sham surgery, model, and homocysteine ​​groups. infused into the caudate putamen of rats to establish models of cerebral hemorrhage in model and homocysteine ​​groups. Homocysteine ​​was injected directly into the brain through the skull at the hematoma hemisphere at 30 minutes after model induction in the homocysteine ​​group. MAIN OUTCOME MEASURES: At 6 , 12, 24, and 72 hours, as well as 1 week, post-surgery, neurological deficits were observed in each group. Brain water content was measured using the dry-wet weight method. Cell apoptosis in tissue surrounding the hematoma was detected utilizing terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). SOD activity and malondialdehyde content in tissue surrounding the hematoma were measured using the xanthine oxidase and thiobarbituric acidMethods .RESULTS: Neurological function was similar between model and homocysteine ​​groups following cerebral hemorrhage (P> 0.05). Brain water content was increased at 12 hours post-surgery, peaked at 3 days, and remained unchanged at 7 days in the model group. The number of apoptotic cells increased in rats with cerebral hemorrhage at 12 hours (P <0.05) , and numbers peaked at 72 hours following model establishment (P <0.05). The time of peak value was identical between model and homocysteine ​​groups. Bank water content was negatively associated with SOD activity (rmodel group = -0.448, P <0.05; group = -0.612, P <0.05), but was positively associated with malondialdehyde content (rmodel group = 0.542, P <0.05; rhomocysteine ​​group = g surgery in model and homocysteine ​​groups. CONCLUSION: Homocysteine ​​aggravates neurological dysfunction and brain edema in rats with cerebral hemorrhage. The mechanisms of action are likely associated with production of oxygen-free radical and cellular apoptosis following cerebral hemorrhage.