Intermittent hypoxia mimicking obstructive sleep apnea aggravates early brain injury following ICH via neuroinflammation and apoptosis

Abstract

Spontaneous intracerebral hemorrhage (ICH) is a subtype of stroke associated with high mortality and morbidity due to the lack of effective therapy. Obstructive sleep apnea (OSA) has been reported to aggravate early brain injury (EBI) and worsen the overall outcome of patients with ICH. However, the precise role of OSA-mediated neuroinflammation and apoptosis following ICH has not been confirmed. The present study aimed to investigate the neuronal damage induced by OSA and the potential molecular mechanisms by which ICH-induced EBI regulates neural apoptosis in a C57BL/6 mouse ICH model. Mortality, neurological score, brain water content and neuronal death were evaluated by Evans blue extravasation, TUNEL staining, ELISA, analysis of reactive oxygen species/lipid peroxidation and western blotting. The results showed that OSA induction decreased survival rate, neurological score and neuron survival and upregulated the protein expression levels of Caspase-3, Bax, cytokines IL-1β, IL-6 and TNF-α and NF-κB, which indicated that OSA-mediated induction of apoptosis and neuroinflammation aggravated neuronal death following ICH. The molecular mechanism was partly dependent on the activating transcription factor/CHOP pathway. Taken together, the results demonstrated that OSA worsens neurological outcomes in mice and increases neuronal death by enhancing neural apoptosis and neuroinflammation.

Hydrogen‑rich saline alleviates early brain injury through inhibition of necroptosis and neuroinflammation via the ROS/HO‑1 signaling pathway after traumatic brain injury

“…Previous studies have demonstrated that neuroinflammation exhibits a vital function in EBI after TBI and enhanced neuroinflammation can aggravate EBI ( 10 , 47-49 ). Activation of the inflammatory process can induce the release of inflammatory cytokines, which include NF-κB, TNF-α IL-6 and IL-1β ( 39 , 50 ). Therefore, ELISA was employed to examine the hippocampal levels of NF-κB, TNF-α IL-6 and IL-1β.…”

Pre‐morbid sleep disturbance and its association with stroke severity: results from the international INTERSTROKE study

“…However, OSA has also been associated with causal aetiologies known to be associated with more severe stroke (e.g., atrial fibrillation, loss of nocturnal blood pressure dipping) [16][17][18]. In addition, sustained OSA symptoms following stroke may negatively impact recovery, via recurrent hypoxic injury, reduced cerebrovascular reactivity or sleep fragmentation affecting rehabilitation engagement [19,35,[42][43][44]. In this study, it was found that a higher OSA score, representative of cumulative, potential OSA symptoms, was associated with initially increased severity but lower mortality after adjusting for this initially increased severity.…”