Sepsis compromises post-ischemic stroke neurological recovery and is associated with sex differences

Life Sci. 2024 Jul 15:349:122721. doi: 10.1016/j.lfs.2024.122721. Epub 2024 May 15.

Abstract

Aims: Infection is a complication after stroke and outcomes vary by sex. Thus, we investigated if sepsis affects brain from ischemic stroke and sex involvement.

Main methods: Male and female Wistar rats, were submitted to middle cerebral artery occlusion (MCAO) and after 7 days sepsis to cecal ligation and perforation (CLP). Infarct size, neuroinflammation, oxidative stress, and mitochondrial activity were quantified 24 h after CLP in the prefrontal cortex and hippocampus. Survival and neurological score were assessed up to 15 days after MCAO or 8 days after CLP (starting at 2 h after MCAO) and memory at the end.

Key findings: CLP decreased survival, increased neurological impairments in MCAO females. Early, in male sepsis following MCAO led to increased glial activation in the brain structures, and increased TNF-α and IL-1β in the hippocampus. All groups had higher IL-6 in both tissues, but the hippocampus had lower IL-10. CLP potentiated myeloperoxidase (MPO) in the prefrontal cortex of MCAO male and female. In MCAO+CLP, only male increased MPO and nitrite/nitrate in hippocampus. Males in all groups had protein oxidation in the prefrontal cortex, but only MCAO+CLP in the hippocampus. Catalase decreased in the prefrontal cortex and hippocampus of all males and females, and MCAO+CLP only increased this activity in males. Female MCAO+CLP had higher prefrontal cortex complex activity than males. In MCAO+CLP-induced long-term memory impairment only in females.

Significance: The parameters evaluated for early sepsis after ischemic stroke show a worse outcome for males, while females are affected during long-term follow-up.

Keywords: Ischemic stroke; Neuroinflammation; Oxidative stress; Sex differences; sepsis.

MeSH terms

  • Animals
  • Brain Ischemia / complications
  • Brain Ischemia / metabolism
  • Female
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Ischemic Stroke* / complications
  • Ischemic Stroke* / metabolism
  • Ischemic Stroke* / pathology
  • Male
  • Oxidative Stress
  • Peroxidase / metabolism
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / pathology
  • Rats
  • Rats, Wistar*
  • Recovery of Function
  • Sepsis* / complications
  • Sepsis* / metabolism
  • Sex Characteristics*
  • Sex Factors

Substances

  • Peroxidase