**1. Introduction**

Cerebrovascular stroke is a leading cause of death and disability in the world [1, 2]. Strokes may be ischemic or hemorrhagic, but most (ca. 85%) are due to interrupted blood flow to the brain, resulting in hypoxia [2]. Thus, the treatment for cerebral ischemia accompanying stroke includes therapies to re-establish blood flow using a thrombolytic agent [3–8]. Delayed reperfusion following cerebral ischemia (>3–4.5 hours) may cause damage to brain capillary endothelial cells [9–11] that can lead to cerebral bleeding and death [12, 13], a process called *reperfusion injury* leading to *hemorrhagic transformation* [14, 15]. Recent evidence has verified that using tissue plasminogen activator (tPA) to dissolve clots is an effective treatment for ischemic stroke, if administered prior to the 3–4.5 hour interval [11, 16, 17]. However, only about 5% of patients with cerebral ischemia arrive at the hospital in time to be treated without causing vascular damage and cerebral hemorrhage, and

a significant number of eligible patients bleed anyway [18]. Thus, preventing injury to the cerebral vasculature when using a thrombolytic agent to induce reperfusion is of great importance. In this study, we provide evidence that reperfusion injury is associated with *oxidative* damage to brain capillary endothelial cells in the presence of elevated calcium. Furthermore, we show that the antioxidant γ-glutamylcysteine [19, 20] (a precursor of glutathione) together with an agent to prevent calcium sequestration inhibit oxidative injury to brain capillaries when co-administered immediately prior to inducing reperfusion for ischemic stroke.
