The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results.

Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these cellular events provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment.

Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage.

Opportunities to interrogate the immune responses in the injured tissue of living patients suffering from acute sterile injuries such as stroke and heart attack are limited. We leveraged a clinical trial of minimally invasive neurosurgery for patients with intracerebral hemorrhage (ICH), a severely disabling subtype of stroke, to investigate the dynamics of inflammation at the site of brain injury over time. Longitudinal transcriptional profiling of CD14 monocytes/macrophages and neutrophils from hematomas of patients with ICH revealed that the myeloid response to ICH within the hematoma is distinct from that in the blood and occurs in stages conserved across the patient cohort.

Divergent Functions of Tissue-Resident and Blood-Derived Macrophages in the Hemorrhagic Brain.

Background And Purpose: Brain tissue-resident microglia and monocyte-derived macrophages (MDMs) are innate immune cells that contribute to the inflammatory response, phagocytosis of debris, and tissue repair after injury. We have previously reported that both microglia and MDMs transition from proinflammatory to reparative phenotypes over days after an intracerebral hemorrhage (ICH). However, their individual functional properties in the brain remain largely unknown.

Leukocyte dynamics after intracerebral hemorrhage in a living patient reveal rapid adaptations to tissue milieu.

Intracerebral hemorrhage (ICH) is a devastating form of stroke with a high mortality rate and few treatment options. Discovery of therapeutic interventions has been slow given the challenges associated with studying acute injury in the human brain. Inflammation induced by exposure of brain tissue to blood appears to be a major part of brain tissue injury.

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage.

Macrophages are a source of both proinflammatory and restorative functions in damaged tissue through complex dynamic phenotypic changes. Here, we sought to determine whether monocyte-derived macrophages (MDMs) contribute to recovery after acute sterile brain injury. By profiling the transcriptional dynamics of MDMs in the murine brain after experimental intracerebral hemorrhage (ICH), we found robust phenotypic changes in the infiltrating MDMs over time and demonstrated that MDMs are essential for optimal hematoma clearance and neurological recovery.