Search

Intracerebral hemorrhage (ICH) is a significant cause of death and disability and current treatment is limited to supportive measures to reduce brain edema and secondary hematoma expansion. Current evidence suggests that the complement cascade is activated early after hemorrhage and contributes to brain edema/injury in multiple ways. The aim of this review is to summarize the most recent literature about the role of the complement cascade after ICH. Primary literature demonstrating complement mediated brain edema and neurologic injury through the membrane attack complex (MAC) as well as C3a and C5a are reviewed. Further, attenuation of brain edema and improved functional outcomes are demonstrated after inhibition of specific components of the complement cascade. Conversely, complement also plays a significant role in neurologic recovery after ICH and in other neurologic disorders. We conclude that the role of complement after ICH is complex. Understanding the role of complement after ICH is essential and may elucidate possible interventions to reduce brain edema and injury. [ABSTRACT FROM AUTHOR]

Background CD47, a glycoprotein on red blood cell membranes, inhibits phagocytosis via interaction with signal regulatory protein α on phagocytes. Our previous research has demonstrated that blocking CD47 accelerates hematoma clearance and reduces brain injury after intracerebral hemorrhage. The current study investigated whether phagocytosis or erythrocyte CD47 impacts hematoma resolution and hydrocephalus development after intraventricular hemorrhage (IVH). Methods Adult (3-month-old) male Fischer 344 rats were intraventricularly injected with 200 μl autologous blood, mixed with either CD47 blocking antibody or isotype IgG, or 200 μl saline as control. In subgroups of CD47 blocking antibody treated rats, clodronate liposomes (to deplete microglia/monocyte-derived macrophages) or control liposomes were co-injected. Magnetic resonance imaging (MRI) was used to evaluate ventricular volume and intraventricular T2* lesion volume (estimating hematoma volume). The brains were harvested after 4 or 72 h for histology to evaluate phagocytosis. Results In adult male rats, CD47 blocking antibody alleviated hydrocephalus development by day 3. In addition, the CD47 blocking antibody reduced intraventricular T2* lesion and T2* non-hypointense lesion size after IVH through day 1 to day 3. Erythrophagocytosis was observed as soon as 4 h after IVH and was enhanced on day 3. Furthermore, intra-hematoma infiltration of CD68, heme oxygenase-1 and ferritin positive phagocytes were upregulated by CD47 blockade by day 3. Clodronate liposomes co-injection caused more severe hydrocephalus and weight loss. Conclusion Blocking CD47 in the hematoma accelerated hematoma clearance and alleviated hemolysis and hydrocephalus development after IVH, suggesting CD47 might be valuable in the future treatment for IVH. • CD47 blocking antibody accelerated hematoma clearance following IVH. • CD47 blocking antibody alleviated IVH-induced hydrocephalus. • CD47 blocking antibody reduced hemolysis in the clot after IVH. [ABSTRACT FROM AUTHOR]