Neuroinflammation in hemorrhagic transformation after tissue plasminogen activator thrombolysis: Potential mechanisms, targets, therapeutic drugs and biomarkers

Hemorrhagic transformation (HT) is a common and serious complication following ischemic stroke, especially after tissue plasminogen activator (t-PA) thrombolysis, which is associated with increased mortality and disability. Due to the unknown mechanisms and targets of HT, there are no effective therapeutic drugs to decrease the incidence of HT. In recent years, many studies have found that neuroinflammation is closely related to the occurrence and development of HT after t-PA thrombolysis, including glial cell activation in the brain, peripheral inflammatory cell infiltration and the release of inflammatory factors, involving inflammation-related targets such as NF-kappa B, MAPK, HMGB1, TLR4 and NLRP3. Some drugs with anti-inflammatory activity have been shown to protect the BBB and reduce the risk of HT in preclinical experiments and clinical trials, including minocycline, fingolimod, tacrolimus, statins and some natural products. In addition, the changes in MMP-9, VAP-1, NLR, sICAM-1 and other inflammatory factors are closely related to the occurrence of HT, which may be potential biomarkers for the diagnosis and prognosis of HT. In this review, we summarize the potential inflammation-related mechanisms, targets, therapeutic drugs, and biomarkers associated with HT after t-PA thrombolysis and discuss the relationship between neuroinflammation and HT, which provides a reference for research on the mechanisms, prevention and treatment drugs, diagnosis and prognosis of HT.

Automated summary

Hemorrhagic transformation (HT) is a common and serious complication following ischemic stroke, especially after tissue plasminogen activator (t-PA) thrombolysis, with neuroinflammation playing a key role in its occurrence. Anti-inflammatory drugs have shown promise in reducing the risk of HT, while certain inflammatory factors may serve as potential biomarkers for diagnosis and prognosis.