Repository of Research and Investigative Information

Repository of Research and Investigative Information

Rafsanjan University of Medical Sciences

Transient brain hypothermia reduces the reperfusion injury of delayed tissue plasminogen activator and extends its therapeutic time window in a focal embolic stroke model

(2017) Transient brain hypothermia reduces the reperfusion injury of delayed tissue plasminogen activator and extends its therapeutic time window in a focal embolic stroke model. Brain Research Bulletin. pp. 85-90. ISSN 0361-9230

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Abstract

It has been reported that restriction of reperfusion after thrombolytic therapy in ischemic stroke may reduce tissue plasminogen activator (tPA) adverse effects and extend its time window. We examined whether shortIt has been reported that restriction of reperfusion after thrombolytic therapy in ischemic stroke may reduce tissue plasminogen activator (tPA) adverse effects and extend its time window. We examined whether short-term and mild local brain cooling can prevent hyperemia and/or adverse effects of delayed tPA in rat embolic stroke model. Male animals were subjected to embolic stroke and then randomly classified into control (saline), tPA (1 mg/kg; i.v.), local hypothermia (LH), and tPA+LH. The drug was injected at 6 h after ischemia. LH was conducted by direct ipsilateral (injured) hemisphere cooling at 6.5 h after stroke and maintained for approximately 30 min. Cerebral blood flow was monitored in duration of 60 minute after tPA administration and hyperemic response was measured. Infarct volume, blood brain barrier (BBB) disruption, edema formation, neurological deficits, and matrix metalloproteinase-9 (MMP-9) level were measured 48 h later. A combination of tPA+LH significantly diminished infarct volume in comparison with the tPA (P < 0.001) and control (P < 0.05) groups. Combination therapy also decreased BBB leakage (P < 0.001), MMP-9 level or edema (P < 0.05) and improved neurological functions at 24 and 48 h after stroke. LH caused a gradual decrease in hyperemic response after thrombolysis compared to the control (P < 0.05) or WA (P < 0.001) groups. LH alone also reduced infarct volume, BBB leakage or edema (P < 0.05). The short-term local brain hypothermia may mitigate reperfusion injury following delayed WA therapy and extend its time window up to 6 h.

Item Type: Article
Keywords: Stroke Reperfusion Hypothermia Tissue plasminogen activator Matrix metalloproteinase acute ischemic-stroke cerebral-artery occlusion hemorrhagic transformation thromboembolic stroke moderate hypothermia infarct volume tpa treatment barrier blood rats Neurosciences & Neurology
Page Range: pp. 85-90
Journal or Publication Title: Brain Research Bulletin
Journal Index: ISI
Volume: 134
Identification Number: https://doi.org/10.1016/j.brainresbull.2017.07.007
ISSN: 0361-9230
Depositing User: مهندس مهدی شریفی
URI: http://eprints.rums.ac.ir/id/eprint/4350

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