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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., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Benign external hydrocephalus (BEH) is characterized by excess cerebrospinal fluid in the frontal subarachnoid spaces in infants evaluated for macrocephaly. We sought to describe the natural history of this disorder, specifically its clinical presentation, disease course and long-term health status impact using the validated, disease-specific Hydrocephalus Outcome Questionnaire (HOQ). Methods: An inception cohort of children >5 and <18 years old, with a history of BEH was assembled by ICD-9 and a key word search of medical and radiology records. Review confirmed the diagnosis of BEH, excluded major medical comorbidities and assessed presentation, radiographic features and head size/growth velocity. The HOQ was administered by mail. Results: We identified 99 patients, 5-12 years old (55% males). Twenty were born prematurely, 12 with <33 weeks gestation. Children presented at an average age of 9 ± 4.8 months (mean ± SD). The presenting complaint was macrocephaly in 65 cases. Other presenting findings were positional head shape deformity and torticollis; 10% had a family history of macrocephaly. Developmental delay was present in 21% of patients (4% verbal, 20% gross motor, 4% fine motor delay). Four patients had small subdural hematomas, none with suspicion of a non-accidental trauma. During clinical reassessment over a mean follow-up of 13 months, the average head percentile was stable and none of the patients developed new subdural hematomas. Gross motor delay resolved in 15/20 and fine motor delay in 4/4 patients. Verbal delay resolved in 2/4 patients, but interestingly, was newly detected in 6 other children. None of the patients required cerebrospinal fluid shunting. The response rate to the HOQ was 25% (median age 7 years, 74% females). The average overall HOQ score was 0.75 ± 0.24 versus 0.68 ± 0.19 for a previously published cohort of shunted hydrocephalic children. Conclusions: BEH patients in this series generally saw resolution of presenting motor developmental delays; however, new verbal delays were detected in a non-trivial number of patients. Quality of life measurements suggest some reduction in health status, but less so than is seen with shunted hydrocephalus. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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]