Mechanisms of Edema Formation After Intracerebral Hemorrhage: Effects of Extravasated Red Blood Cells on Blood Flow and Blood-Brain Barrier Integrity

Background and Purpose— Red blood cell (RBC) lysis contributes to brain edema formation after intracerebral hemorrhage (ICH), and RBC hemolysate (oxyhemoglobin) has been implicated to be a spasminogen in subarachnoid hemorrhage. Whether cerebral ischemia contributes to brain edema formation after ICH remains unclear, however. The aims of this study were to test whether extravasation of RBCs induces cerebral ischemia and/or blood-brain barrier disruption in a rat ICH model characterized by perihematomal brain edema. Methods— In this study, 87 pentobarbital-anesthetized Sprague-Dawley rats were used. In each animal, saline, packed RBCs, or lysed RBCs were injected into the right caudate nucleus. Sham injections served as controls. Regional cerebral blood flow, brain water and ion contents, blood-brain barrier integrity, and plasma volume were measured. Results— Intraparenchymal infusion of lysed RBCs caused severe brain edema by the first day but did not induce ischemic cerebral blood flows. In contrast, blood-brain barrier permeability increased during the first day after infusion of lysed RBCs (a 3-fold increase) and 3 days after infusion of packed RBCs (a 4-fold increase). Conclusions— These results suggest that ischemia is not present at 24 or 72 hours after hematoma induction by injection of intact or lysed RBCs. RBC constituents that appear after delayed lysis, however, increase blood-brain barrier permeability, which contributes to edema formation.