Hematology and Inflammatory Signaling of Intracerebral Hemorrhage

Although the dawn of targeted treatments for primary intracerebral hemorrhage (ICH) seems in sight, many biological questions remain, which will drive the next clinical trial and animal model steps. The objective of this review is to describe the role of inflammatory signaling molecules and the clot lysis cascade, and the role of edema as a surrogate marker for inflammation.The primary injury of hematoma formation and its expansion within brain parenchyma is mechanical damage to brain tissue causing disruption of white matter tracts and, at the most severe, resulting in herniation. The tissue at the epicenter of the clot is not likely to be salvaged because of dissection of blood, causing direct and rapid tissue destruction.1 The size of the epicenter remains unknown, some evidence suggests it is small when compared with ischemic stroke,2 thus secondary mechanisms of injury may be disproportionally important in ICH.The secondary injury of ICH can be considered as emanating from a time-dependent progression of 3 intertwined degenerative cascades in the regions both adjacent to the hematoma: inflammation, red cell lysis, and thrombin production (coagulation cascade; Figure). All 3 lead to disruption of the blood–brain barrier, resulting in cerebral edema directly or indirectly, and death of brain parenchymal cells.Figure. Mechanisms underlying brain edema and neuronal injury after intracerebral hemorrhage and potential therapeutic targets. H-O indicates heme-oxygenase; MAPKs, mitogen-activated protein kinases; PARs, protease-activated receptors; and PPARγ agonist, peroxisome proliferator–activated receptor γ agonist.These pathways are all feasible therapeutic targets as injury occurs over hours to weeks. Thus, perihematomal tissue is potentially salvageable by countering degenerative events at the appropriate time interval. Apoptosis and neuronal necrosis are common end points of the degenerative pathways, but without good clinical surrogates. Cerebral edema, on the contrary, may be a reasonable target. InflammationICH brings the immediate infiltration of …