| ObjectiveHypoxic-ischemic brain damage (HIBD) is a commom disease in clinic, especially in the perinatal period. HIBD is a major cause of mortality and neurological damage in infants and children. There was any marked breakthrough in prevention and treatment of this disease in recent years because of its complex mechanism. Lately, the important role of disbalance of excitotory / inhibitory neurotransmission in the brain neuron damage caused by the hypoxia-ischemia (HI) insult has been paied more and more attention. Sodium hydroxybutyrate (GHB) is interim metabolite of gama-amino butyratyric acide( GAB A) , the sodium salt of y-hydroxybutyric acid, an analogue of GABA ( an inhibitory neuro-transmitter in the brain) ,can produce marked central nervous suppression. Recent research performed in our lab suggested that GHB could produce neuronpro-tective effect on brain ischemia/reperfusion injury in gerbils. We investigated the physical development and growth, the capability of learning and memory, the brain neuropathology , Bcl-2 and Bax expression in the cortex and hipp-ocampal CA1 region neuron , and the gene expression of N-methyl-D-aspartate receptor uint NR1 ,NR2A and NR2B in the hippocampal. We try to explore the brianprotective effects of GHB on the hypoxic-ischemic encephalopathy and and its mechanism.Materials and Methods1 HIBD model performed, animal grouping and drug administration , 1,1 HIBD model performed Under ether anesthesia, postnatal 7-day Sprague Dawley (SD)rats had leftcarotid arteries ligated followed by 2. 0 h of hypoxic (8% oxygen). S group underwent same operational procedure except the ligation and hypoxia insult.1.2 Animal grouping and drug administrationpostnatal 7-day rats were randomly assigned to control group(C group) , sham group ( S group) and sodium hydroxybutyrate group (y group) , -y group was further randomly divided into -yl,-y2 and yS group. Every group was further divided into several subgroups again according various observational time point after HI insult. Saline was administered by i. p. injection immediately after HI insult and three times daily thereafter for maximum 7d in group C,the injecting volume was 0. 2ml/10g bodyweight, and the same administration was also given at 4h after HI insult. Also, sodium hydroxybutyrate was administered by the same methods, The dosage of sodium hydroxybutyrate was 50, 100 and 200mg/ kg for -y1,y2,y3 group, respectively.2 The effect of HI insult on the brain morphology, physical development and growth and capability of learning and memory and the intervention of GHB2.1 Animal grouping and drug administrationAnimal grouping and drug administration were described as that in the segment 1.2. Group C ,S and r1,y2 and y3 were further divided into four groups according the time point 3d,7d,14d and 28d after HI insult, n =20.2. 2 Observational index and method2. 2. 1 Animal physical development and growthThe increase times of bodyweight and body length.2.2.2 Survival rateThe survival rate in every group at 28 d after HI insult2. 2. 3 Capability of learning and memoryAt 27d after HI insult,the capability of learning and memory of rat were detected by Y-maze and done again after 24h. The detail index were as follows. (1) The rate of reaching the learning criteria. (2) The total test times before reaching criteria. (3 ) The total reaction times before reaching criteria. (4) The active avoiding reaction rate. (5)The correct reaction rate.2.2.4 The observation of left/right hemisphere weight, water-contained of left hemishere and incidence of cavum formed andEight survival rats in every group were chosen randomly to been decapitated and took out the brain, observed gross brain morphologic impaired. Then the left and right hemisphere were departed, and the fresh brain were weighed as wet weight followed put their into 70C ~ 80C oven for 24h, afterward the dried brain tissue were weighed and as dried weight. Brain water-contained = ( wet weight - dried weight) / wet weight.2. 2. 5 The...
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