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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.1
- 수록면
- 31 - 40 (10page)
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초록· 키워드
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Recently, we reported that the A3 adenosine receptor (A3AR) agonist LJ529 (2-chloro-N6-(3-iodobnzyl)-5’-N-methylcarbamoyl-4’-thioadenosine) reduces cerebral ischemic injury via inhibition of recruitment of peripheral inflammatory cells into ischemic brain lesion. A3AR agonists, however, are known to possess anti-platelet activity, which may deter the combination therapy with tissue plasminogen activator for the therapy of cerebral ischemic stroke. Thus, the present study investigates the neuroprotective/anti-ischemic effect of a synthetic seco-nucleoside, LMT497 ((S)-2-((R)-1-(2-chloro-6-(3-iodobenzylamino)-9H-purin-9-yl)-2-hydroxyethoxy)-3-hydroxy-N-methylpropanamide) with little anti-platelet activity. LMT497 neither showed A3AR binding activity nor anti-platelet activity. In our present study LMT497 significantly attenuated the injury/death of cortical neurons exposed to oxygen-glucose deprivation (OGD) followed by re-oxygenation (R). LMT497 significantly reduced the ascending cellular level of reactive oxygen species under ischemic conditions by increasing the superoxide dismutase (SOD) levels. LMT497 also inhibited the migration of microglia which mediates inflammatory responses in ischemia. In rats subjected to middle cerebral artery occlusion (MCAO, 1.5 h) followed by reperfusion, LMT497 largely reduced brain infarction volume, and edema, and improved neurological score. Therapeutic efficacy of LMT497 was obtained by twice treatments even at 10 h and 18 h after the onset of ischemia. Collectively, LMT497 could be a therapeutic drug candidate with a wide therapeutic time window for the treatment of cerebral ischemic stroke.
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참고문헌 (31)
참고문헌 신청
Brouns R / 2009 / The complexity of neurobiological processes in acute ischemic stroke / Clin Neurol Neurosurg 111:483~495
Chapman SN / 2014 / Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke / Vasc Health Risk Manag 10:75~87
The NINDS t-PA Stroke Study Group / 1997 / Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke / Stroke 28:2109~2118
Ginsberg MD / 2008 / Neuroprotection for ischemic stroke:past, present and future / Neuropharmacology 55:363~389
Hallevi H / 2008 / Antiplatelet therapy and the risk of intracranial hemorrhage after intravenous tissue plasminogen activator therapy for acute ischemic stroke / Arch Neurol 65:575~576
Chapman SN / 2014 / Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke / Vasc Health Risk Manag 10:75~87
The NINDS t-PA Stroke Study Group / 1997 / Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke / Stroke 28:2109~2118
Ginsberg MD / 2008 / Neuroprotection for ischemic stroke:past, present and future / Neuropharmacology 55:363~389
Hallevi H / 2008 / Antiplatelet therapy and the risk of intracranial hemorrhage after intravenous tissue plasminogen activator therapy for acute ischemic stroke / Arch Neurol 65:575~576
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