Protective effect of topiramate on hypoxic-ischemic brain injury in neonatal rat

OBJECTIVE@#To explore protective effect of topiramate (TPM) on hypoxic-ischemic brain injury.@*METHODS@#A total of 360 neonatal rats were selected then randomly divided into sham operation group, ischemia and hypoxia group, conventional treatment group and degradation therapy group (n=90). After surgical treatment, sham and ischemic hypoxia group were treat with normal saline; conventional treatment group was received TPM solution 100 mg/kg, 2 times/d; degradation therapy group received TPM solution 150 mg/kg, 2 times/d, per 3 d treatment each dosage was reduced 50 mg/kg, the lowest reduced to 50 mg/kg. Four groups received continuous treatment for 10 d. After treatment for 1 d, 4 d, 7 d, 10 d the cerebral edema, neuron-specific enolase (NSE) and γ-aminobutyric acid (GABA) levels and cognitive abilities of four groups were observed.@*RESULTS@#After 1 d, 4 d of treatment, the brain water content and NSE levels in ischemia and hypoxia group, the conventional treatment group and the degradation therapy group were significantly higher than that in sham group (P<0.05), the brain water content and NSE levels of the conventional treatment group and the degradation therapy group were significantly lower than that in the ischemic hypoxia group (P<0.05). GABA levels and learning ability of the ischemia and hypoxia group, the conventional treatment group and degradation therapy group were significantly lower than the sham group (P<0.05), the GABA levels and learning ability of the conventional treatment group and degradation therapy group were significantly higher than the ischemia and hypoxia group (P<0.05). After 7 d, 10 d of treatment, the brain water content and NSE levels in the sham operation group, the conventional treatment group and degradation therapy group were significantly lower than the ischemia and hypoxia group (P<0.05), while the GABA levels and learning ability of these three groups were significantly higher than that in the ischemia and hypoxia group (P<0.05), the GABA levels in the conventional treatment group were significantly higher than degradation therapy group (P<0.05); After 10 d of treatment, the GABA levels of the conventional treatment group were significantly higher than the sham group, the learning ability of the degradation therapy group and sham operation group were significantly higher than the conventional treatment group (P<0.05).@*CONCLUSIONS@#The correct amount of short-term TPM has protective effect on hypoxic-ischemic brain injury, but long-term or excessive use may cause new damage to the brain and reduce the cognitive ability.

Construction of Saccharomyces cerevisiae Mutant Deficient in adh2 and ald6 Genes / 微生物学通报

The purpose of this investigation is to improve ethanol production and decrease acetate formation in Saccharomyces cerevisiae strain YS2-?adh2.The strain YS2-?adh2 with deleted alcohol dehydrogenase Ⅱ(adh2) gene was isolated in our lab with higher ethanol production than that of the strain YS2.The ace-taldehyde dehydrogenase Ⅵ(ald6) gene encoded a cytosolic acetaldehyde dehydrogenase,a key enzyme of the pyruvate dehydrogenase(PDH) bypass,transfers acetaldehyde to acetate.To disrupt ald6 gene of the strain YS2-?adh2,ald6 gene targeting cassettes were synthesized by long flanking homology PCR(LFH-PCR) and then were transformed into YS2-?adh2 mutants by LiAc/SS Carrier DNA/PEG method.Positive transformants were selected with G418 and further confirmed by PCR.Once correctly integrated into the genome,the selective marker was rescued by transforming the plasmid pSH65 into the positive transformants and inducing the Cre expression with a Cre/loxP-mediated marker removal procedure.We named the ald6 gene knocked-out strain as YS2-?adh2-?ald6 which has a 12.5% higher ethanol production and a 18% lower acetate formation compared to the strain YS2.