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

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 (1mg/kg; i.v.), local hypothermia (LH), and tPA+LH. The drug was injected at 6h after ischemia. LH was conducted by direct ipsilateral (injured) hemisphere cooling at 6.5h after stroke and maintained for approximately 30minutes. Cerebral blood flow was monitored in a duration of 60minute 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 48h 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 <0.01) and improved neurological functions at 48h after the stroke. LH caused a gradual decrease in hyperemic response after thrombolysis compared to the control (P <0.05) or tPA (P <0.001) groups. LH alone also reduced infarct volume, BBB leakage or edema (P <0.01). The short-term local brain hypothermia may mitigate reperfusion injury following delayed tPA therapy and extend its time window up to 6h. PMID: 28710023 [PubMed - as supplied by publisher]
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research