Feng Lu1, Takehiro Nakamura2, Naohiko Okabe1, Naoyuki Himi1, Emi Nakamura-Maruyama1, Takashi Shiromoto1, Kazuhiko Narita1, Ikuko Tsukamoto3, Guohua Xi4, Richard F Keep4, Osamu Miyamoto1. 1. Department of Physiology 2, Kawasaki Medical School, Kawasaki Medical University, Kurashiki, Okayama, Japan. 2. Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu, Kagawa, Japan. Electronic address: tanakamu@kms.ac.jp. 3. Department of Pharmacobioinformatics, Kagawa University Faculty of Medicine, Miki, Kagawa, Japan. 4. Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan.
Abstract
BACKGROUND: A previous study in our laboratory showed the neuroprotective effects of COA-Cl, a novel synthesized adenosine analog, in a rat cerebral ischemia model. The purpose of the present study was to evaluate the neuroprotective effects of COA-Cl in intracerebral hemorrhage (ICH), another common type of stroke, and investigate potential mechanisms of action. METHODS: Adult Sprague-Dawley rats received an injection of 100 µl autologous whole blood into the right basal ganglia. COA-Cl (30 µg/kg) was injected intracerebroventricularly 10 minutes after ICH. A battery of motor deficit tests were performed at 1 day, 3 days, 5 days, and 7 days after ICH. To investigate the mechanism of action, brain water content, TUNEL staining and 8-OHdG immunostaining, and ELISA (to assess oxidative stress) were used. RESULTS: COA-Cl treatment significantly attenuated sensorimotor deficits and reduced brain edema 1 day after ICH. Furthermore, the numbers of perihematomal TUNEL- and 8-OHdG-positive cells were significantly decreased in COA-Cl treated ICH rats. CONCLUSIONS: These results indicate that COA-Cl has neuroprotective effects in ICH. Furthermore, our study provides evidence that COA-Cl may reduce oxidative stress, which may be one mechanism underlying its neuroprotective effects.
BACKGROUND: A previous study in our laboratory showed the neuroprotective effects of COA-Cl, a novel synthesized adenosine analog, in a ratcerebral ischemia model. The purpose of the present study was to evaluate the neuroprotective effects of COA-Cl in intracerebral hemorrhage (ICH), another common type of stroke, and investigate potential mechanisms of action. METHODS: Adult Sprague-Dawley rats received an injection of 100 µl autologous whole blood into the right basal ganglia. COA-Cl (30 µg/kg) was injected intracerebroventricularly 10 minutes after ICH. A battery of motor deficit tests were performed at 1 day, 3 days, 5 days, and 7 days after ICH. To investigate the mechanism of action, brain water content, TUNEL staining and 8-OHdG immunostaining, and ELISA (to assess oxidative stress) were used. RESULTS:COA-Cl treatment significantly attenuated sensorimotor deficits and reduced brain edema 1 day after ICH. Furthermore, the numbers of perihematomal TUNEL- and 8-OHdG-positive cells were significantly decreased in COA-Cl treated ICHrats. CONCLUSIONS: These results indicate that COA-Cl has neuroprotective effects in ICH. Furthermore, our study provides evidence that COA-Cl may reduce oxidative stress, which may be one mechanism underlying its neuroprotective effects.