Perihematomal Neurovascular Protection: Blocking HSP90 Reduces Blood Infiltration Associated with Inflammatory Effects Following Intracerebral Hemorrhage in Rates.

Abstract

The active hemorrhage surrounding the hematoma is caused by the infiltration of blood into the cerebral parenchyma through the ruptured vessel, including the compromised blood-brain barrier (BBB). This process is thought to be mainly driven by inflammation and serves as a significant pathological characteristic that contributes to the neurological deterioration observed in individuals with intracerebral hemorrhage (ICH). Heat shock protein 90 (HSP90) exhibits abnormally high expression levels in various diseases and is closely associated with the onset of inflammation. Here, we found that blocking HSP90 effectively alleviates the inflammatory damage to BBB and subsequent bleeding around the hematoma. We have observed increased HSP90 levels in the serum of patients with ICH and the perihematoma region in ICH rats. Treatment with anti-HSP90 drugs (Geldanamycin and radicicol) effectively reduced HSP90 levels, resulting in enhanced neurological outcomes, decreased hematoma volume, and prevented peripheral immune cells from adhering to the BBB and infiltrating the brain parenchyma surrounding the hematoma in ICH rats. Mechanistically, anti-HSP90 therapy alleviated BBB injury caused by ICH-induced inflammation by suppressing TLR4 signaling. The study highlights the potential of anti-HSP90 therapy in mitigating BBB disruption and hemorrhage surrounding the hematoma, providing new insights into the management of ICH by targeting HSP90.