1. Academic Validation
  2. Hydrochloride fasudil attenuates brain injury in ICH rats

Hydrochloride fasudil attenuates brain injury in ICH rats

  • Transl Neurosci. 2020 Apr 20;11(1):75-86. doi: 10.1515/tnsci-2020-0100.
Limin Li 1 Xiaoli Lou 1 Kunlun Zhang 1 Fangping Yu 1 Yingchun Zhao 1 Ping Jiang 1
Affiliations

Affiliation

  • 1 Department of Neurology, The Affiliated Shanghai Songjiang Central Hospital of Shanghai Jiao Tong University, Central Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract

Aim: The aim of this study was to investigate the neuroprotective effects of hydrochloride fasudil (HF) in rats following intracerebral hemorrhage (ICH).

Methods: Male Wistar rats were randomly divided into four groups: normal, sham-operated, ICH, and ICH/HF. ICH was induced by injection of non-anticoagulant autologous arterial blood into the right caudate nucleus. The levels of Rho-associated protein kinase 2 (ROCK2) mRNA and protein around the site of the hematoma were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. The levels of interleukin-6 and tumor necrosis factor-α in serum were detected by ELISA. The inflammatory cells and changes in the neuronal morphology around the hematoma were visualized using hematoxylin and eosin and Nissl staining. Brain edema was measured by comparing wet and dry brain weights.

Results: Following ICH, the levels of ROCK2 were significantly increased from day 1 to day 7. The levels of ROCK2 were significantly lower in rats treated with HF than in controls. The levels of inflammatory cytokines and brain water content were significantly higher in rats treated with HF than in controls. Administration of HF significantly reduced the levels of inflammatory cytokines and brain water content from day 1 to day 7. In the acute phase of ICH, a large number of neutrophils infiltrated the perihematomal areas. In comparison with the ICH group, the ICH/HF group showed markedly fewer infiltrating neutrophils on day 1. Nissl staining showed that ICH caused neuronal death and loss of neurons in the perihematomal areas at all time points and that treatment with HF significantly attenuated neuronal loss.

Conclusions: HF exerts neuroprotective effects in ICH rats by inhibiting the expression of ROCK2, reducing neutrophil infiltration and production of inflammatory cytokines, decreasing brain edema, and attenuating loss of neurons.

Keywords

Rho-associated protein kinase; brain injury; hydrochloride fasudil; inflammation; intracerebral hemorrhage.

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