Ischemic preconditioning attenuates brain edema after experimental intracerebral hemorrhage

Ischemic preconditioning (IPC) provides protection against subsequent severe ischemic injury. A recent study found that cerebral IPC prolongs bleeding time. In this study, we examined whether IPC protects against intra-cerebral hemorrhage (ICH)-induced brain edema formation and whether IPC affects blood coagulation. There were three sets of experiments in this study. In the first set, male Sprague-Dawley rats were preconditioned with either 15 min of left middle cerebral artery occlusion, an IPC stimulus, or a sham operation. Three days later, rats received an infusion of autologous whole blood in the ipsilateral or contralateral caudate. Rats were killed 24 h later for brain water content measurement. In the second set, rats underwent 15 min of IPC or a sham operation. Three days later, rats were used for bleeding and thrombin clotting time tests. In the third set, the levels of p44/42 mitogen-activated protein kinases (MAPKs), heme oxygenase-1 (HO-1), transferrin (Tf), and transferrin receptor (TfR) in the brain 24 or 72 h after IPC were examined. We found that IPC reduced ICH-induced brain edema when blood was injected into the ipsilateral caudate but it did not when blood was injected into the contralateral caudate. IPC resulted in prolongation of bleeding time and thrombin clotting time. IPC also induced the activation of p44/42 MAPKs and upregulation of HO-1, Tf, and TfR levels in the ipsilateral caudate. These results suggest that IPC protects against ICH-induced brain edema formation and decreases blood coagulation. The protection of IPC against ICH is mainly due to local factors in the brain and may be related to activation of p44/42 MAPKs and upregulation of HO-1, Tf, and TfR.