Combined systemic thrombolysis with alteplase and early hyperbaric oxygen therapy in experimental embolic stroke in rats: relationship to functional outcome and reduction of structural damage.

ABSTRACT

INTRODUCTION: The only causal therapy in ischemic stroke is thrombolysis with recombinant tissue plasminogen activator (rtPA), but it is feasible only for few patients, and new therapies are needed. This study investigates the effects of systemic thrombolysis with rtPA combined with hyperbaric oxygen therapy (HBOT) in embolic stroke in rats. METHODS: In 22 male Wistar rats, an embolic ischemic stroke was induced. The animals were randomized to one of four groups control, thrombolysis alone, HBOT sequential or HBOT parallel with thrombolysis. HBOT (2.4 ATA, 1 h) started 45 min (sequential) or 120 min (parallel) after stroke. rtPA was given intravenously 120 min after stroke onset. Functional tests were performed after stroke induction and after treatment. After 6 h infarct volume and intracerebral hemorrhagic complications were assessed. RESULTS: Compared to the control group only the combination of HBOT and thrombolysis significantly improved the functional outcome (p=0.03) and reduced the infarct volume (p=0.01), whereas thrombolysis alone did not show a significant benefit. In all treatment groups there was a trend towards fewer hemorrhagic transformations. CONCLUSION: Hyperbaric oxygen in combination with thrombolysis shows neuroprotection in acute ischemic stroke in rats by reducing infarct volume and improving functional outcome in the early poststroke period.