Macrophages play a key role in early blood brain barrier reformation after hypothermic brain injury

Abstract

The inflammatory response following traumatic injury to the central nervous system (CNS) includes the infiltration of large numbers of macrophages. This response has been implicated in both ongoing tissue damage as well as recovery following CNS injury. We investigated the role of invading macrophages on one important aspect of tissue repair in the brain, the reformation of the blood brain barrier (BBB). We used liposomal clodronate to deplete monocytes and tissue macrophages. This method led to a marked reduction in the accumulation of F4/80-expressing cells at sites of hypothermic brain injury in a murine model. The integrity of the blood brain barrier over time following injury was assessed by permeability of fluorescent labeled albumin. The reduction in macrophages at the injury site was accompanied by a delay in early reformation of the blood brain barrier. In control animals the permeability of the BBB to FITC-labeled albumin returned to normal levels by seven days post-injury. In macrophage-depleted mice leakage of albumin was still observed at seven days post-injury. These results suggest that macrophages play an important role in early post-traumatic reformation of the BBB.