Brain Injury And Hypothermia As A Neuroprotective Stratery In The Acute Phase Of Subarachnoid Hemorrhage

Objective: Brain injury in the acute phase of subarachnoid hemorrhage (AmSAH) is the mainly mortal reason .but research poorly performed. There is almost no effective treatment for brain injury in the acute phase of AmSAH. Hypothermia as a neuroprotective stratery could induce brain edema in ischemic brain damage. The aims of the recent research is to explore the mechanisms of brain injury and neuroprotection of hypothermia in the acute phase of AmSAH.Methodes:Sprague-Dawley rats prechiasmatic SAH model was used for researching brain injury in the acute phase of AmSAH . SAH models had been divided two group: normal body temperature and hypothermia , every group had four subgroups according to decrease in cerebral blood flow and duration, Including mSAH2h, mSAH4h, sSAH2h, sSAH4h, mHSAH2h, mHSAH4h, sHSAH2h, sHSAH4h. Contral rats (SO) received saline solution.The following parameters of brain tissue or mitochondria were determined: 1) Ultrastructure of CA1 section of hippocampus was observed by electro mi croscope;2) Rate of state 4 and state 3 in the presence of malate and glutate by using Clark Oxygen Electrode;3) ATP synthesis of brain mitochondria by fluorescin- fluorescin enzyme fluorometry;4) Transmembrane potential in mitochondria from brain by fluorometric probe;5) ROS generation rate in brain mitochondria by fluorometric probe;6) Mn-SOD enzyme activity by enzymological method;7) The malondialdehyde (MDA) of brain mitochondria byusing TBA method;8) IV-cPLA2 and HIF—la mRNA expression in brain tissue using RT-PCR.Results: 90 SD rats were used for producing prechiasmatic SAH model. We had successfully produced 72 SAH models , 12 animals died . There were edema and necrosis of neuron in normal body temperature of SAH group. Edema and necrosis of neuron alleviated in hypothermia SAH group. Every normal body temperature of SAH group vs.SO : State 3: * P<0.05 mSAH2h;**P<0.01 sSAH2h , mSAH4h;***P<0.001 sSAH4h. State 4: * PO.05 sSAH2h;**P<0.01 mSAH4h;*"p<0.001 sSAH4h. RCR **PO.01 mSAH2h, sSAH2h andmSAH4h;***P<0.001 sSAH4h. ATP synthesis: **P<0.01 mSAH4h;***PO.001 sSAH4h.Every normal body temperature of SAH group vs. SAH hypothermia group: State 4: * PO.05, sSAH2h **PO.01 mSAH4h;RCR: ***PO.001 mSAH2h, sSAH2h, mSAH4h. ROS generation: ***PO.001 mSAH4h , sSAH4h . MDA: P<0.05 sSAH4h. Transmembranepotential:**P0.01sSAH2h;***P0.001mSAH4h , sSAH4h. SAH group vs. SAH hypothermia group : ROS generation: **PO.01 mSAH4h. ***PO.001 sSAH4h. Transmembrane potential: PO.05 mSAH4h , **P<0.01 sSAH4h. Every SAH group vs.SO: IV-cPLA2mRNA * PO.05 mSAH4h , **PO.01 sSAH4h. HEF-la mRNA **P<0.01 sSAH4h. SAH group vs. SAH hypothermia group : * PO.05 mSAH4h , sSAH4h. SAH group vs. SAH hypothermia group : **PO.01 sSAH2h ***P<0.001 sSAH4h.Conclusion: 1) Rat prechiasmatic SAH model can mimic change of global cerebral blood flow in the acute phase of AmSAH. it show edema and necrosis of neuron and suit for reseaching brain injury in the acute phase of AmSAH . Hypothermia can alleviate edema and necrosis of neurons and show neuroprotection in the acute phase of subarachnoid hemorrhages .2)Both lipid peroxidation and hydrolysis of phospholipid membrane cause braininjury in the acute phase of AmSAH . When mitochondrial membrane was damaged , electron -leak pathway increased and ROS generation in brain mitochondria increased. Oxygen free radical cause lipid peroxidation. Hypothermia can decrease the global energy metabolic rat , so it cause electron -leak pathway and ROS generation decreasing . Hypothermia can alleviate lipid peroxidation from brain by reducing ROS generation . 3) The increased level of calcium-dependent cytosolic phospholipase A2 mRNA can aggravate hydrolysis of mitochondrial membrane phospholipids , this conduce to ROS generation. Hypothermia can reduce the level of cPLA2 mRNA and stable mitochondrial membrane . 4) Hypothermia can enhance the level of HIF-la mRNA,we speculate that hypothermia enhance brain tissue ability to resist injury from hypo - and hyper perfusion by HIF-1.