title: COA-Cl, a Novel Synthesized Nucleoside Analog, Exerts Neuroprotective Effects in the Acute Phase of Intracerebral Hemorrhage.
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.
authors: Department of Physiology 2, Kawasaki Medical School, Kawasaki Medical University, Kurashiki, Okayama, Japan.
authors: Feng
authors: F
authors: Lu
authors: Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu, Kagawa, Japan. Electronic address: tanakamu@kms.ac.jp.
authors: Takehiro
authors: T
authors: Nakamura
authors: Department of Physiology 2, Kawasaki Medical School, Kawasaki Medical University, Kurashiki, Okayama, Japan.
authors: Naohiko
authors: N
authors: Okabe
authors: Department of Physiology 2, Kawasaki Medical School, Kawasaki Medical University, Kurashiki, Okayama, Japan.
authors: Naoyuki
authors: N
authors: Himi
authors: Department of Physiology 2, Kawasaki Medical School, Kawasaki Medical University, Kurashiki, Okayama, Japan.
authors: Emi
authors: E
authors: Nakamura-Maruyama
authors: Department of Physiology 2, Kawasaki Medical School, Kawasaki Medical University, Kurashiki, Okayama, Japan.
authors: Takashi
authors: T
authors: Shiromoto
authors: Department of Physiology 2, Kawasaki Medical School, Kawasaki Medical University, Kurashiki, Okayama, Japan.
authors: Kazuhiko
authors: K
authors: Narita
authors: Department of Pharmacobioinformatics, Kagawa University Faculty of Medicine, Miki, Kagawa, Japan.
authors: Ikuko
authors: I
authors: Tsukamoto
authors: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan.
authors: Guohua
authors: G
authors: Xi
authors: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan.
authors: Richard F
authors: RF
authors: Keep
authors: Department of Physiology 2, Kawasaki Medical School, Kawasaki Medical University, Kurashiki, Okayama, Japan.
authors: Osamu
authors: O
authors: Miyamoto
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: C552550:2Cl-C.OXT-A; D000975:Antioxidants; D015415:Biomarkers; D018696:Neuroprotective Agents; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D000241:Adenosine
keywords: Intracerebral hemorrhage; adenosine analog; neuroprotection; rat