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  • Title: [Effect of local mild hypothermia on expression of aquaporin-4 following intracerebral hemorrhage in rats].
    Author: Dai DW, Wang DS, Li KS, Mao Y, Zhang LM, Duan SR, Sheng L.
    Journal: Zhonghua Yi Xue Za Zhi; 2006 Apr 04; 86(13):906-10. PubMed ID: 16759517.
    Abstract:
    OBJECTIVE: To examined the effect of local mild hypothermia on the expression of aquaporin-4 (AQP-4) following intracerebral hemorrhage (ICH) in rats and clarified the mechanism of hypothermia on brain edema formation following ICH. METHODS: Two hundreds and forty male Wistar rats were randomly divided into two groups: the intracerebral hemorrhage (ICH) group, in which autologous arterial blood were stereotaxically injected into right caudate nucleus; the local mild hypothermia (ICH + H) group, in which the rats were given 4 h local mild hypothermia after the injection of blood. Each group was divided into 6 subgroups: control, 6 h, 24 h, 72 h, 5 d and 7 d after operation; Brain water content was determined by dry-wet weight method and the permeability of BBB was measured by Evans-Blue extravasation. RT-PCR and Western blot were respectively used to evaluate AQP-4 mRNA and protein expression. RESULTS: In ICH group, compared with control, ICH significantly increased BWC, the permeability of BBB and the expression of AQP-4 mRNA, all began at 6 h and peaked at 72 h (P < 0.01), the increased protein expression of AQP-4 began at 24 h and also peaked at 72 h (P < 0.01). AQP-4 expression positively correlated, both at the mRNA and the protein level, with the permeability of BBB (r = 0.78 and r = 0.76 respectively). In ICH + H group, compared with ICH group, the elevation of BWC, BBB permeability and AQP-4 protein expression were strongly attenuated at all time point by hypothermia treatment (P < 0.01), while AQP-4 mRNA levels demonstrated a modest attenuation from 48 h. At 72 h, AQP-4 mRNA optical density (A) decreased from 1.25 +/- 0.03 (ICH group) to 1.04 +/- 0.02 (P < 0.01), AQP-4 protein expression (A) decreased from 0.77 +/- 0.08 (ICH group) to 0.25 +/- 0.04 (P < 0.01). CONCLUSIONS: This study indicates that BBB breakdown can increase the expression of AQP-4; local mild hypothermia can significantly reduce brain edema formation after ICH by suppressing the elevation of AQP-4 protein expression; Inhibition of BBB breakdown and the elevation of AQP-4 protein expression with local mild hypothermia appear to contribute to brain protection in this model.
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