Temporally distinct myeloid cell responses mediate damage and repair after cerebrovascular injury

Cerebrovascular injuries can cause severe edema and inflammation that adversely affect human health. Here, we observed that recanalization after successful endovascular thrombectomy for acute large vessel occlusion was associated with cerebral edema and poor clinical outcomes in patients who experienced hemorrhagic transformation. To understand this process, we developed a cerebrovascular injury model using transcranial ultrasound that enabled spatiotemporal evaluation of resident and peripheral myeloid cells. We discovered that injurious and reparative responses diverged based on time and cellular origin. Resident microglia initially stabilized damaged vessels in a purinergic receptor-dependent manner, which was followed by an influx of myelomonocytic cells that caused severe edema. Prolonged blockade of myeloid cell recruitment with anti-adhesion molecule therapy prevented severe edema but also promoted neuronal destruction and fibrosis by interfering with vascular repair subsequently orchestrated by proinflammatory monocytes and proangiogenic repair-associated microglia (RAM). These data demonstrate how temporally distinct myeloid cell responses can contain, exacerbate and ultimately repair a cerebrovascular injury.

Automated summary

Positive vascular recanalization after endovascular thrombectomy may lead to cerebral edema and worsened clinical outcomes, especially in patients with hemorrhagic transformation. Resident microglia initially stabilize damaged vessels, followed by an influx of myelomonocytic cells causing severe edema. Prolonged blockade of myeloid cell recruitment can prevent severe edema but also interfere with vascular repair.