Secondary White Matter Injury Mediated by Neuroinflammation after Intracerebral Hemorrhage and Promising Therapeutic Strategies of Targeting the NLRP3 Inflammasome

Intracerebral hemorrhage (ICH) is a severe neurological condition with high rates of mortality and disability. Recent research indicates that white matter injury (WMI) significantly contributes to motor dysfunction following ICH. Neuroinflammation, mediated by microglia and astrocytes, plays a crucial role in the secondary WMI that occurs after ICH. The NLRP3 inflammasome exacerbates neuroinflammation and brain injury post-ICH. It is activated in both microglia and astrocytes, playing a significant role in neuroinflammation. Inhibiting NLRP3 inflammasome may reduce WMI by shifting microglia and astrocytes to an anti-inflammatory state after ICH. This review explores how neuroinflammation, influenced by the NLRP3 inflammasome, worsens secondary WMI after ICH and discusses potential therapeutic targets. Targeting the NLRP3 inflammasome could offer new strategies for treating WMI and promoting white matter repair in ICH patients.

• 1
  White matter injury (WMI) significantly contributes to neurological dysfunction after intracerebral hemorrhage (ICH), often more than previously recognized gray matter injuries.
• 2
  The NLRP3 inflammasome exacerbates neuroinflammation and brain injury after ICH by activating in microglia and astrocytes, promoting a pro-inflammatory phenotype.
• 3
  Inhibiting NLRP3 inflammasome activation may attenuate WMI by polarizing microglia and astrocytes towards an anti-inflammatory phenotype, thus promoting white matter repair after ICH.