Effect of isoflurane post-treatment on tPA-exaggerated brain injury in a rat ischemic stroke model

Abstract

BACKGROUND: Intravenous tissue-type plasminogen activator (tPA) is recognized as the standard treatment for ischemic stroke. However, its narrow therapeutic window and association with an increased risk of intracranial hemorrhage have required caution when used. In this context, several approaches are required to deal with the shortcomings of such a double-edged drug. Anesthetics are known to protect against ischemic reperfusion injury, and their protective role in ischemic post-conditioning is crucial for reducing ischemia-related injury. The aim of this study was to assess the effect of isoflurane post-treatment on intracranial hemorrhage and cerebral infarction after tPA treatment for transient cerebral ischemia. METHODS: Cerebral ischemia was modeled in male Sprague-Dawley rats (n = 32) by occluding the right middle cerebral artery for 1 h, followed by intravenous tPA administration. Rats were randomly divided into control and isoflurane post-treatment group, and isoflurane post-treatment group was post-treated by administering 1.5% isoflurane for 1 h from the start of reperfusion. Twenty-four h after reperfusion, neurobehavioral changes were assessed. The extent of cerebral infarction and intracranial hemorrhage were also assessed by quantification of infarction volume and cerebral hemoglobin concentration from brain tissue, respectively. RESULTS: Neurobehavioral testing showed better functional outcomes in the isoflurane post-treatment group than the control group. The extent of cerebral infarction and intracranial hemorrhage were both reduced in isoflurane post-treatment group compared to control group. CONCLUSIONS: Isoflurane post-treatment may mitigate infarction volume and intracranial hemorrhage in tPA-exaggerated brain injury. Our findings provide an encouraging novel approach for enhancing clinical outcomes in tPA-exaggerated brain injury.