Peripheral cytokine interleukin-10 alleviates perihematomal edema after intracerebral hemorrhage via interleukin-10 receptor/JAK1/STAT3 signaling

CNS Neurosci Ther. 2024 Jun;30(6):e14796. doi: 10.1111/cns.14796.

Abstract

Aims: The extent of perihematomal edema following intracerebral hemorrhage (ICH) significantly impacts patient prognosis, and disruption of the blood-brain barrier (BBB) exacerbates perihematomal edema. However, the role of peripheral IL-10 in mitigating BBB disruption through pathways that link peripheral and central nervous system signals remains poorly understood.

Methods: Recombinant IL-10 was administered to ICH model mice via caudal vein injection, an IL-10-inhibiting adeno-associated virus and an IL-10 receptor knockout plasmid were delivered intraventricularly, and neurobehavioral deficits, perihematomal edema, BBB disruption, and the expression of JAK1 and STAT3 were evaluated.

Results: Our study demonstrated that the peripheral cytokine IL-10 mitigated BBB breakdown, perihematomal edema, and neurobehavioral deficits after ICH and that IL-10 deficiency reversed these effects, likely through the IL-10R/JAK1/STAT3 signaling pathway.

Conclusions: Peripheral IL-10 has the potential to reduce BBB damage and perihematomal edema following ICH and improve patient prognosis.

Keywords: Interleukin‐10; blood–brain barrier; intracerebral hemorrhage; perihematomal edema; tight junction.

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Brain Edema* / drug therapy
  • Brain Edema* / etiology
  • Cerebral Hemorrhage* / complications
  • Cerebral Hemorrhage* / drug therapy
  • Cerebral Hemorrhage* / metabolism
  • Interleukin-10* / metabolism
  • Janus Kinase 1* / antagonists & inhibitors
  • Janus Kinase 1* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin-10*
  • STAT3 Transcription Factor* / metabolism
  • Signal Transduction* / drug effects
  • Signal Transduction* / physiology

Substances

  • STAT3 Transcription Factor
  • Janus Kinase 1
  • Interleukin-10
  • Stat3 protein, mouse
  • Receptors, Interleukin-10
  • Jak1 protein, mouse
  • IL10 protein, mouse