Effects of focal mild hypothermia on thrombin-induced brain edema formation and the expression of protease activated receptor-1, matrix metalloproteinase-9 and aquaporin 4 in rats

Gao,Dapeng; Ding,Feifan; Lei,Gongwen; Luan,Guohui; Zhang,Shibao; Li,Kesen; Wang,Desheng; Zhang,Liming; Dai,Dawei

doi:10.3892/mmr.2014.3111

Effects of focal mild hypothermia on thrombin-induced brain edema formation and the expression of protease activated receptor-1, matrix metalloproteinase-9 and aquaporin 4 in rats

Authors:
- Dapeng Gao
- Feifan Ding
- Gongwen Lei
- Guohui Luan
- Shibao Zhang
- Kesen Li
- Desheng Wang
- Liming Zhang
- Dawei Dai
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Affiliations: Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China
Published online on: December 18, 2014 https://doi.org/10.3892/mmr.2014.3111
Pages: 3009-3014

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Abstract

Hypothermia is an effective neuroprotective treatment for brain injury caused by intracerebral hemorrhage (ICH). It is reported to reduce brain edema and neuronal cell death. Thrombin, a coagulation protease released from blood clots, is critical in brain edema formation following ICH. Protease activated receptor‑1 (PAR‑1), matrix metalloproteinase‑9 (MMP‑9) and aquaporin 4 (AQP4) are edema‑associated mediators that have been implicated in ICH pathology. In the present study, thrombin was used to induce brain edema in adult male Sprague‑Dawley rats. Differences between a focal mild hypothermic group (33±0.5˚C) and a normothermic group (37˚C) were investigated. Following hypothermia, brain water content and blood‑brain barrier (BBB) disruption was assessed at 6, 24 and 48 h and subsequently at 3, 5 and 7 days. At the same time, the mRNA and protein expression of PAR‑1, MMP‑9 and AQP4 were also determined. It was identified that brain water content and BBB disruption increased at 6 h and reached a maximal level at 24 h in the normothermic group. The mRNA and protein expression levels of PAR‑1, MMP‑9 and AQP4 started to increase at 24 h and reached a maximal level at 48 h. Focal mild hypothermia tended to significantly reduce brain water content, BBB disruption and PAR‑1, MMP‑9 and AQP expression at 24 and 48 h. The present data suggest that focal mild hypothermia is an effective treatment for edema formation through moderation of the mRNA and protein expression of PAR‑1, MMP‑9 and AQP4.

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