Accumulation of macromolecules in brain parenchyma in acute phase of cerebral infarction/reperfusion

Ischemia-reperfusion injury is induced by recovery of blood flow after ischemia. This phenomenon is a main cause of ischemic brain injury. The integrity of the blood-brain barrier (BBB) fails after cerebral ischemia and reperfusion. Further elucidation of this phenomenon promotes to develop treatment strategies for ischemia-reperfusion injury. In the present study, we attempted to examine the time-dependent change of ischemia-reperfusion injury in relation to BBB disorders at acute phase in a transient middle cerebral artery occlusion (t-MCAO) model rat as a cerebral infarction and reperfusion model. Brain cell damage after the reperfusion was assessed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. To clarify a time-dependent change of the integrity of BBB, fluorescein isothiocyanate (FITC)-dextran (150 kDa) was injected intravenously into t-MCAO rats, and time-dependent localization of FITC-dextran was monitored in ex vivo. As a result, obvious brain damage was firstly observed at 3 h after reperfusion following 1 h of MCAO. In contrast, the leakage of FITC-dextran from cerebral vessels was observed immediately after the reperfusion. The present data suggest that the integrity of BBB failed prior to the occurrence of serious brain damage induced by ischemia-reperfusion, and that macromolecules such as water-soluble Polymers and proteins which cannot pass through the BBB under normal condition would reach brain parenchyma at early stage after reperfusion. These findings would be useful to establish a novel treatment strategy for reperfusion injury after cerebral infarction.