Calcitriol protects the Blood-Brain Barrier integrity against ischemic stroke and reduces vasogenic brain edema via antioxidant and antiapoptotic actions in rats

Abstract

BackgroundVasogenic brain edema is the most important complication of ischemic stroke that aggravates primary brain injury. Ischemia-Reperfusion (IR)-induced Blood-Brain Barrier (BBB) impairment limits the use of recombinant tissue plasminogen activator (r-tPA) by increasing the possibility of hemorrhagic transformation and contributing to vasogenic edema and neuroinflammation. This study examined the effects of post-ischemic treatment with calcitriol on cerebral infarction, vasogenic edema formation and BBB disruption in a rat model of ischemic stroke. MethodsMale Sprague-Dawley rats were divided into three main groups, including the sham, IR + vehicle and IR + calcitriol groups. Transient focal cerebral ischemia was induced by a 60-min-long occlusion of the left middle cerebral artery. The infarct volume, brain edema, BBB permeability and antioxidant enzyme activities were evaluated 24 h after ischemia. Immunohistochemical analysis was conducted to investigate cell apoptosis and Brain-Derived Neurotrophic Factor (BDNF) protein expression five days after ischemia. ResultsCompared to the IR + vehicle group, the IR + calcitriol group showed a reduced brain infarction volume, attenuated brain edema formation and improved BBB function. These protective effects were followed by the upregulation of antioxidant enzyme activities in the brain tissue. Additionally, a diminished cell apoptosis and an increased BDNF immunoreactivity were obtained in the IR + calcitriol group. ConclusionCalcitriol may reduce brain injury and attenuate vasogenic edema by upregulating antioxidant enzymes activities, reducing cell apoptosis and increasing BDNF protein in the brain tissue in a rat model of ischemic stroke.