Subacute Phase of Brain Injury

During the subacute phase (hours after ischemia), the migration of leukocytes into the compromised brain tissue (Section 5.5.1) amplifies inflammatory signaling cascades.24,34-36 Inflammatory mediators and proteases such as the matrix metallopro-teinases (MMP-2 and -9) and interleukins (IL-1) are thought to mediate damage during the inflammatory phase of ischemia.24,37,38 Indeed, inhibitors of MMP-9 are neuroprotective in experimental stroke, and MMP-9 knockout mice show much smaller ischemic lesions.38 Proinflammatory genes such as COX-2 and IL-1P are up-regulated in the ischemic brain;35,36 COX-2 activity has been implicated in the pathogenesis of neuronal cell death in ischemia and other diseases, but the mechanism by which COX-2 exacerbates cell death is unknown.

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