A rho-kinase inhibitor prevents apoptosis-induced neuronal cell death following transient focal ischemia in rats

Tatsushi Kamiya, Toshiki Inaba, Chikako Nito, Masayuki Ueda, Kengo Kato, Satoshi Suda, Takeshi Hayashi, Kentaro Deguchi, Toru Yamashita, Yoshihide Sehara, Atsushi Tsuchiya, Zhe Zhang Han, Violeta Lukic, Yasuo Katayama, Koji Abe

Research output: Contribution to journalArticle

Abstract

Background and aims: Recently, it has been reported that rho-kinase that participates in the regulation of vascular tonus, spasm, and remodeling in response to smooth muscle constriction, is involved in the atherosclerosis, inflammation, and hypertention (1). Furthermore, rho-kinase is involved in nitric oxide (NO), free radical, resulting in the neuronal cell death (2). Nevertheless, the mechanism of rho-kinase on the ischemic brain have not been fully understood. The aim of this study is, therefore, to determine whether a newly rho-kinase inhibitor, fasudil, which is a myosin light chain kinase inhibitor and have strong inhibition of rho-kinase, would prevent neuronal cell death following transient focal ischemia in rats compared to a free radical scavenger, edaravone , which is the first clinical neuroprotective agent used in Japan for the treatment of acute stroke patients. Methods: Sprague-Dawley rats were subjected to MCAo using an intraluminal suture technique for 90 minutes (3). The rats were reperfused for 24 hours and decapitated for infarct and edema analysis (4). Animals were randomly divided into the following four groups. (I) vehicle-treated control group (II) low dose of fasudil (3.0 mg/kg)-treated group (III) high dose of fasudil (10.0 mg/kg)-treated group (IV) edaravone-treated group. A rho-kinase inhibitor-treated animals received a continuous injection of fasudil (3.0 or 10.0 mg/kg) intravenously for 60 minutes after the onset of ischemia, while vehicle-treated groups received same dose of vehicle. Edaravone-treated animals received twice injection of edaravone (3.0 mg/kg) intravenously immediately after the reperfusion and 30 minutes after reperfusion. During ischemia, temporal muscle and rectal temperatures were monitored and maintained at 37 degrees in the experimental animals. Neurological symptom evaluations (posture and hemiplegia) were performed immediately before infarct and edema analysis. Furthermore, cortical cerebral blood flow was measured during ischemia and reperfusion. Results: The cortical and striatal infarct volume in the edaravone-treated group was significantly less than those in the vehicle-treated control group I (p

Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue numberSUPPL. 1
Publication statusPublished - Nov 13 2007

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rho-Associated Kinases
Cell Death
Ischemia
Apoptosis
Reperfusion
Edema
Cerebrovascular Circulation
Temporal Muscle
Myosin-Light-Chain Kinase
Corpus Striatum
Suture Techniques
Control Groups
Free Radical Scavengers
Injections
Hemiplegia
Symptom Assessment
Spasm
Neuroprotective Agents
Posture
Constriction

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

A rho-kinase inhibitor prevents apoptosis-induced neuronal cell death following transient focal ischemia in rats. / Kamiya, Tatsushi; Inaba, Toshiki; Nito, Chikako; Ueda, Masayuki; Kato, Kengo; Suda, Satoshi; Hayashi, Takeshi; Deguchi, Kentaro; Yamashita, Toru; Sehara, Yoshihide; Tsuchiya, Atsushi; Han, Zhe Zhang; Lukic, Violeta; Katayama, Yasuo; Abe, Koji.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 27, No. SUPPL. 1, 13.11.2007.

Research output: Contribution to journalArticle

Kamiya, T, Inaba, T, Nito, C, Ueda, M, Kato, K, Suda, S, Hayashi, T, Deguchi, K, Yamashita, T, Sehara, Y, Tsuchiya, A, Han, ZZ, Lukic, V, Katayama, Y & Abe, K 2007, 'A rho-kinase inhibitor prevents apoptosis-induced neuronal cell death following transient focal ischemia in rats', Journal of Cerebral Blood Flow and Metabolism, vol. 27, no. SUPPL. 1.
Kamiya, Tatsushi ; Inaba, Toshiki ; Nito, Chikako ; Ueda, Masayuki ; Kato, Kengo ; Suda, Satoshi ; Hayashi, Takeshi ; Deguchi, Kentaro ; Yamashita, Toru ; Sehara, Yoshihide ; Tsuchiya, Atsushi ; Han, Zhe Zhang ; Lukic, Violeta ; Katayama, Yasuo ; Abe, Koji. / A rho-kinase inhibitor prevents apoptosis-induced neuronal cell death following transient focal ischemia in rats. In: Journal of Cerebral Blood Flow and Metabolism. 2007 ; Vol. 27, No. SUPPL. 1.
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AU - Kamiya, Tatsushi

AU - Inaba, Toshiki

AU - Nito, Chikako

AU - Ueda, Masayuki

AU - Kato, Kengo

AU - Suda, Satoshi

AU - Hayashi, Takeshi

AU - Deguchi, Kentaro

AU - Yamashita, Toru

AU - Sehara, Yoshihide

AU - Tsuchiya, Atsushi

AU - Han, Zhe Zhang

AU - Lukic, Violeta

AU - Katayama, Yasuo

AU - Abe, Koji

PY - 2007/11/13

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N2 - Background and aims: Recently, it has been reported that rho-kinase that participates in the regulation of vascular tonus, spasm, and remodeling in response to smooth muscle constriction, is involved in the atherosclerosis, inflammation, and hypertention (1). Furthermore, rho-kinase is involved in nitric oxide (NO), free radical, resulting in the neuronal cell death (2). Nevertheless, the mechanism of rho-kinase on the ischemic brain have not been fully understood. The aim of this study is, therefore, to determine whether a newly rho-kinase inhibitor, fasudil, which is a myosin light chain kinase inhibitor and have strong inhibition of rho-kinase, would prevent neuronal cell death following transient focal ischemia in rats compared to a free radical scavenger, edaravone , which is the first clinical neuroprotective agent used in Japan for the treatment of acute stroke patients. Methods: Sprague-Dawley rats were subjected to MCAo using an intraluminal suture technique for 90 minutes (3). The rats were reperfused for 24 hours and decapitated for infarct and edema analysis (4). Animals were randomly divided into the following four groups. (I) vehicle-treated control group (II) low dose of fasudil (3.0 mg/kg)-treated group (III) high dose of fasudil (10.0 mg/kg)-treated group (IV) edaravone-treated group. A rho-kinase inhibitor-treated animals received a continuous injection of fasudil (3.0 or 10.0 mg/kg) intravenously for 60 minutes after the onset of ischemia, while vehicle-treated groups received same dose of vehicle. Edaravone-treated animals received twice injection of edaravone (3.0 mg/kg) intravenously immediately after the reperfusion and 30 minutes after reperfusion. During ischemia, temporal muscle and rectal temperatures were monitored and maintained at 37 degrees in the experimental animals. Neurological symptom evaluations (posture and hemiplegia) were performed immediately before infarct and edema analysis. Furthermore, cortical cerebral blood flow was measured during ischemia and reperfusion. Results: The cortical and striatal infarct volume in the edaravone-treated group was significantly less than those in the vehicle-treated control group I (p

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