COA-Cl, a Novel Synthesized Nucleoside Analog, Exerts Neuroprotective Effects in the Acute Phase of Intracerebral Hemorrhage

• Published in: Journal of stroke and cerebrovascular diseases 2016-11, Vol.25 (11), p.2637-2643
• Main Authors: Lu, Feng, PhD, Nakamura, Takehiro, MD, PhD, Okabe, Naohiko, MD, PhD, Himi, Naoyuki, PhD, Nakamura-Maruyama, Emi, PhD, Shiromoto, Takashi, MD, Narita, Kazuhiko, PhD, Tsukamoto, Ikuko, PhD, Xi, Guohua, MD, Keep, Richard F., PhD, Miyamoto, Osamu, MD, PhD
• Format: Article
• Language: English
• Subjects: Adenosine - administration & dosage; Adenosine - analogs & derivatives; Adenosine - pharmacology; adenosine analog; Animals; Antioxidants - pharmacology; Apoptosis - drug effects; Behavior, Animal - drug effects; Biomarkers - metabolism; Body Water - metabolism; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain - physiopathology; Brain Edema - metabolism; Brain Edema - pathology; Brain Edema - prevention & control; Cardiovascular; Cerebral Hemorrhage - drug therapy; Cerebral Hemorrhage - metabolism; Cerebral Hemorrhage - pathology; Cerebral Hemorrhage - physiopathology; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; Disease Models, Animal; Injections, Intraventricular; Intracerebral hemorrhage; Male; Motor Activity - drug effects; Neurology; neuroprotection; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Oxidative Stress - drug effects; rat; Rats, Sprague-Dawley; Time Factors
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2016.07.006

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.