Inhibition of Rho kinase by hydroxyfasudil attenuates brain edema after subarachnoid hemorrhage in rats

Department of Physiology and Pharmacology, Loma Linda University, 11234 Anderson Street, Loma Linda, CA 92354, USA.
Neurochemistry International (Impact Factor: 3.09). 02/2012; 60(3):327-33. DOI: 10.1016/j.neuint.2011.12.014
Source: PubMed


The blood-brain barrier (BBB) disruption and brain edema are important pathophysiologies of early brain injury after subarachnoid hemorrhage (SAH). This study is to evaluate whether Rho kinase (Rock) enhances BBB permeability via disruption of tight junction proteins during early brain injury. Adult male rats were assigned to five groups; Sham-operated, SAH treated with saline, a Rock inhibitor hydroxyfasudil (HF) (10 mg/kg) treatment at 0.5 h after SAH, HF treatment at 0.5 and 6 h (10 mg/kg, each) after SAH, and another Rock inhibitor Y27632 (10 mg/kg) treatment at 0.5 h after SAH. The perforation model of SAH was performed and neurological score and brain water content were evaluated 24 and 72 h after surgery. Evans blue extravasation, Rock activity assay, and western blotting analyses were evaluated 24 h after surgery. Treatment of HF significantly improved neurological scores 24 h after SAH. Single treatment with HF and Y27632, and two treatments with HF reduced brain water content in the ipsilateral hemisphere. HF reduced Evans blue extravasation in the ipsilateral hemisphere after SAH. Rock activity increased 24 h after SAH, and HF reversed the activity. SAH significantly decreased the levels of tight junction proteins, occludin and zonula occludens-1 (ZO-1), and HF preserved the levels of occluding and ZO-1 in ipsilateral hemisphere. In conclusion, HF attenuated BBB permeability after SAH, possibly by protection of tight junction proteins.

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    • "However , this value was markedly increased on day 5 after bleeding. In agreement with these observations, RhoA and ROCK mRNAs are upregulated in the basilar artery of SAH rat models [30] [35]. In summary, we show here that inhibition of LTCCs, PLC, SR refilling and ROCK selectively and significantly reduces the potentiation of the sustained component of the depolarization-evoked contraction observed on day 5 after SAH. "
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    • "A total of 25 adult male Sprague-Dawley rats (Harlan, Indianapolis, IN) weighing 260–320 g were used for the study. The endovascular perforation model of SAH was performed as previously described [5,6]. Briefly, rats were anesthetized, intubated and kept on artificial ventilation during surgery. "
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