Assessment of blood-brain barrier integrity by dynamic contrast enhanced MRI in transient middle cerebral artery occlusion model after localized brain cooling

Abstract

Introduction: Localized brain cooling before reperfusion reportedly helps to reduce the inflammatory response and recover the function of brain neurons in stroke therapy. Little is known about the effects of localized brain cooling on permeability changes associated with alterations to the blood-brain barrier (BBB).Purpose: The purpose of this study was to evaluate the effects of localized brain cooling on BBB permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast enhanced- (DCE-) MRI.Materials and method: Thirty rats were divided into three groups (10 rats each): control group, localized cold-saline (20°C) infusion group, and localized warm-saline (37°C) infusion group. The left middle cerebral artery (MCA) was occluded for 1 h in anesthetized rats, followed by 3 h of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 min after MCA occlusion. DCE-MRI investigations were performed after 3 h and 24 h of reperfusion. Four pharmacokinetic parameters of the Tofts model (wash-in rate [Ktrans], wash-out rate [Kep], leakage-space volume [Ve], and plasma-space volume [Vp]) were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1–9 after tMCAO. Myeloperoxidase (MPO) immunohistochemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain.Result: There was a statistically significant decrease in Ktrans and Kep at the infarction site in the cold-saline group compared with the control group (P < 0.05) and a decrease in Kep that approached significance in the cold-saline group compared with the warm-saline group (Kep: cortex, P = 0.0892 basal ganglia, P = 0.0925). The percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (P < 0.05). However, behavioral testing did not reveal a statistically significant difference among the three groups.Conclusion: Localized brain cooling can inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model.