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

Abstract

BACKGROUND AND PURPOSE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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

• Authors: Rong Jin, Adam Y Xiao, Shan Liu, Min Wang, Guohong Li
• Journal: Stroke (Stroke) Vol. 49 Issue 7 Pg. 1708-1718 (07 2018) ISSN: 1524-4628 [Electronic] United States
• PMID: 29844028 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2018 American Heart Association, Inc.

Chemical References

• Fibrinolytic Agents
• Neuroprotective Agents
• Taurine
• Tissue Plasminogen Activator

Topics

• Animals
• Disease Models, Animal
• Fibrinolytic Agents (adverse effects, therapeutic use)
• Infarction, Middle Cerebral Artery (drug therapy)
• Intracranial Hemorrhages (chemically induced, drug therapy)
• Male
• Neuroprotective Agents (therapeutic use)
• Rats
• Stroke (drug therapy)
• Taurine (therapeutic use)
• Tissue Plasminogen Activator (adverse effects, therapeutic use)