Curcumin Treatment Improves Breathing and Neuroinflammation after C2 Hemisection

Breathing is often impaired following spinal cord injury (SCI). In the initial hours-weeks after SCI, a cascade of inflammatory events is activated resulting in tissue damage, apoptosis, and formation of the glial scar which prevents axon regeneration. Curcumin is the biologically active polyphenol of turmeric and is a powerful anti-inflammatory supplement which has been shown to reduce inflammation, oxidation, fibrosis and improve locomotion after SCI. We hypothesized that daily curcumin treatment would reduce neuroinflammation and improve tidal volume and minute ventilation in a preclinical model of cervical SCI. To test this hypothesis, male Sprague-Dawley rats received a left-sided C2 hemisection. Rats were given daily curcumin (100mg/kg; I.P.; n=6) or vehicle (DMSO + saline; I.P.; n=5) injections for 8 days (beginning the day of injury) and then once a week for 3 weeks. Using whole-body plethysmography, we evaluated ventilation in awake, freely behaving animals during normoxia (21% FiO 2 ) and respiratory challenge (10.5% FiO 2 , 7% FiCO 2 ) before and weekly after injury for 4 weeks. Curcumin-treated animals showed no difference in tidal volume (% pre-injury) compared to vehicle controls at weeks 1 ( P=0.7577), 2 ( P=0.8215), or 3 ( P=0.8428). However, 4 weeks post-C2Hx, curcumin-treated animals showed an increased tidal volume relative to vehicle-treated controls ( P=0.0378). At 4 weeks, vehicle treated animals displayed a reduction in tidal volume compared to pre-injury (-32.76 ± 6.12%, P=0.0002), while curcumin-treated rats showed no differences in tidal volume relative to pre-injury values (-17.29 ± 6.42%, P=0.054). During respiratory challenge, curcumin and vehicle treated animals showed no differences in tidal volume at any time point. No differences in minute ventilation (% pre-injury) were found between groups during normoxia or challenge. Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) were quantified to evaluate the number of astrocytes and microglia within the cervical cord 4 weeks post-SCI. Curcumin treated animals showed fewer astrocytes ( p<0.0001) and microglia ( p<0.0001) within the C3-C5 spinal cord compared to vehicle treated rats. Our data show that curcumin is an effective treatment to attenuate both neuroinflammation and respiratory deficits after C2 hemisection. In ongoing studies, we are evaluating the effects of curcumin treatment in a pre-clinical rodent model of cervical spinal cord contusion and future studies are focused on testing novel approaches to improve the bioavailability of curcumin. This work was supported by funding from the National Institutes of Health, grant numbers: R00 HL143207-01 (KAS) and UL1TR001436 (TCH) and the Craig H. Neilsen Inclusion Supplement 993667 (KAS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.