Combination approaches to attenuate hemorrhagic transformation after tPA thrombolytic therapy in patients with poststroke hyperglycemia/diabetes.

Abstract

To date, tissue type plasminogen activator (tPA)-based thrombolytic stroke therapy is the only FDA-approved treatment for achieving vascular reperfusion and clinical benefit, but this agent is given to only about 5% of stroke patients in the USA. This may be related, in part, to the elevated risk of symptomatic intracranial hemorrhage, and consequently limited therapeutic time window. Clinical investigations demonstrate that poststroke hyperglycemia is one of the most important risk factors that cause intracerebral hemorrhage and worsen neurological outcomes. There is a knowledge gap in understanding the underlying molecular mechanisms, and lack of effective therapeutics targeting the severe complication. This short review summarizes clinical observations and experimental investigations in preclinical stroke models of the field. The data strongly suggest that interactions of multiple pathogenic factors including hyperglycemia-mediated vascular oxidative stress and inflammation, ischemic insult, and tPA neurovascular toxicity in concert contribute to the BBB damage-intracerebral hemorrhagic transformation process. Development of combination approaches targeting the multiple pathological cascades may help to attenuate the hemorrhagic complication.