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Stroke. 2018 Jul;49(7):1708-1718. doi: 10.1161/STROKEAHA.118.020747. Epub 2018 May 29.

Taurine Reduces tPA (Tissue-Type Plasminogen Activator)-Induced Hemorrhage and Microvascular Thrombosis After Embolic Stroke in Rat.

Jin R1, Xiao AY2, Liu S1, Wang M1, Li G3,4,2.

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From the Department of Neurosurgery, Neuroscience Institute, Penn State Hershey Medical Center (R.J., S.L., M.W., G.L.).
Department of Molecular and Cellular Physiology (A.Y.X., G.L.), Louisiana State University Health Sciences Center, Shreveport.
From the Department of Neurosurgery, Neuroscience Institute, Penn State Hershey Medical Center (R.J., S.L., M.W., G.L.)
Department of Neurosurgery (G.L.).



Taurine (2-aminoethansulfolic amino acid) exerts neuroprotective actions in experimental stroke. Here, we investigated the effect of taurine in combination with delayed tPA (tissue-type plasminogen activator) on embolic stroke.


Rats subjected to embolic middle cerebral artery occlusion were treated with taurine (50 mg/kg) at 4 hours in combination with tPA (10 mg/kg) at 6 hours. Control groups consisted of ischemic rats treated with either taurine (50 mg/kg) or saline at 4 hours or tPA (10 mg/kg) alone at 2 or 6 hours after middle cerebral artery occlusion.


We found that combination treatment with taurine and tPA robustly reduced infarct volume and neurological deficits 3 days after stroke, whereas treatment with taurine alone had a less-significant protective effect. tPA alone at 6 hours had no effects on infarct volume but instead induced intracerebral hemorrhage. The combination treatment with taurine prevented tPA-associated hemorrhage and reduced intravascular deposition of fibrin/fibrinogen and platelets in downstream microvessels and hence improved microvascular patency. These protective effects are associated with profound inhibition of CD147 (cluster of differentiation 147)-dependent MMP-9 (matrix metalloproteinase-9) pathway in ischemic brain endothelium by taurine. Notably, targeted inhibition of CD147 by intracerebroventricular injection of the rat CD147 siRNA profoundly inhibited ischemia-induced and tPA-enhanced MMP-9 activity in ischemic brain endothelium and blocked tPA-induced cerebral hemorrhage. Finally, the combination treatment with taurine and tPA improved long-term outcome at least 45 days after stroke compared with saline-treated group.


Our results suggest that taurine in combination with tPA may be a clinically feasible approach toward future attempts at combination stroke therapy.


cluster of differentiation 147; ischemic stroke; rats; taurine; thrombolysis; thrombosis; tissue-type plasminogen activator

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