Objective: Traumatic brain injury (TBI) induced the gastrointestinal inflammation that is associated with TBI-related morbidity and mortality. Carbon monoxide-releasing molecule (CORM)-3 is a water-soluble exogenous carbon monoxide that exerts protective effects against inflammation-induced pyroptosis. We investigated the gastrointestinal inflammation in a rodent model of traumatic brain injury (TBI) with subsequent hemorrhagic shock and resuscitation (HSR), as well as effects of CORM-3 using an intestinal injection on both gut and brain.
Methods: Following exposure to TBI plus HSR, rats were administrated with CORM-3 (8 mg/kg) through an intestinal injection after resuscitation immediately. The pathological changes and pyroptosis in the gut were measured at 24 h and 30 day post-trauma. We also assessed the intestinal and cortical CO content, as well as IL-1β and IL-18 levels in the serum within 48 h after trauma. We then explored pathological changes in the ventromedial prefrontal cortex (vmPFC) and neurological behavior deficits on 30 day post-trauma.
Results: After TBI + HSR exposure, CORM-3-treated rats presented significantly decreased pyroptosis, more CO content in the jejunum, and lower IL-1β, IL-18 levels in the serum at 24 h after trauma. Moreover, the rats treated with CORM-3 exerted ameliorated jejunal and vmPFC injury, enhanced learning/memory ability and exploratory activity, improved anxiety-like behaviors than the TBI + HSR-treated rats on 30 day post-trauma.
Conclusion: These experimental data demonstrated and bidirectional gut-brain interactions after TBI, anti-inflammatory effects of CORM-3, which may improve late outcomes after brain injury.
Keywords: Carbon monoxide; Jejunum; Neuroprotection; Pyroptosis; Traumatic brain injury.
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