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Attenuation of cerebral vasospasm following experimental subarachnoid hemorrhage by the bronchodilator KMUP-3. 2013

William Winardi, and Chih-Jen Wang, and Chih-Lung Lin, and Shu-Chuan Wu, and Hung-Pei Tsai, and Yen-Hsin Kuo, and Ming-Yen Lee, and Ing-Jun Chen, and Aij-Lie Kwan
Poznan University of Medical Sciences, Poznan, Poland.

Delayed cerebral vasospasm is a main cause of morbidity and mortality as well as poor outcome in patients following aneurysmal subarachnoid hemorrhage (SAH). In this study, the effect of the bronchodilator KMUP-3 (7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) on basilar artery narrowing, neurological outcome, and expression of rhoA/rho kinase II (ROCKII), rhoA, and protein kinase C (PKC) γ proteins were evaluated in a rat model of SAH. SAH was induced by double injection of autologous blood into the cistern magna on days 0 and 3. KMUP-3 was administered (0.3 mg/kg/day) by osmotic minipumps implanted subcutaneously (beginning day -3 in pretreatment group and at 1 h after the initiation of the first autologous blood injection in the treatment group). Neurological outcome was assessed by ambulation and placing/stepping reflex responses at 48 h after the second injection of autologous blood. Tissue morphology and protein expression were conducted on day 7 post-day 0 injection. Both KMUP-3 treatment regimens significantly improved neurological outcome and completely attenuated basilar artery narrowing as well as reduced the enhancement of ROCKII, rhoA, and PKCγ protein expression in rats subjected to SAH, compared with normal and untreated SAH rats. These results suggest that KMUP-3 may be a novel agent for the treatment of cerebral vasospasm following SAH.

UI MeSH Term Description Entries
D008124 Locomotion Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. Locomotor Activity,Activities, Locomotor,Activity, Locomotor,Locomotor Activities
D008297 Male Males
D009460 Neurologic Examination Assessment of sensory and motor responses and reflexes that is used to determine impairment of the nervous system. Examination, Neurologic,Neurological Examination,Examination, Neurological,Examinations, Neurologic,Examinations, Neurological,Neurologic Examinations,Neurological Examinations
D010880 Piperidines A family of hexahydropyridines.
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D012018 Reflex An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord.
D001993 Bronchodilator Agents Agents that cause an increase in the expansion of a bronchus or bronchial tubes. Bronchial-Dilating Agents,Bronchodilator,Bronchodilator Agent,Broncholytic Agent,Bronchodilator Effect,Bronchodilator Effects,Bronchodilators,Broncholytic Agents,Broncholytic Effect,Broncholytic Effects,Agent, Bronchodilator,Agent, Broncholytic,Agents, Bronchial-Dilating,Agents, Bronchodilator,Agents, Broncholytic,Bronchial Dilating Agents,Effect, Bronchodilator,Effect, Broncholytic,Effects, Bronchodilator,Effects, Broncholytic
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression

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