Co-delivery of curcumin-resveratrol-carnosic acid complex promotes neurogenesis and cognitive recovery in a rodent model of repeated mild traumatic brain injury.

Repeated traumatic brain injury has grown in importance as sports-related injuries have increased. Repetitive mild TBI (rmTBI) increases the risk of developing neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, as well as chronic comorbidities like PTSD, depression, substance abuse and neuroendocrine functions. However, no effective therapeutic strategies have been reported for the effective management of TBI. Herein, we examined the effectiveness of co-delivery of the phytonutrients curcumin, trans-resveratrol, and carnosic acid as a bioavailable complex (CGM+) in managing rmTBI in the rodent model. The rats were randomly assigned to sham, rmTBI, and CGM+ (300 mg/kg b.wt.) groups for a total of 21 days. On Days 6 and 7, all animals, except those in the sham group, were subjected to repeated mild traumatic brain injury (rmTBI). The CGM+ group received supplementation throughout the 21 days, while the other groups received a vehicle. Neurological severity score (NSS) was assessed 24 h after the last injury, and behavioral tests were completed within 14 days post-injury. Samples for the biochemical analysis were collected after euthanasia. CGM+ supplementation significantly decreased the sensory-motor deficits associated with rmTBI. Following TBI, the CGM+ group demonstrated enhanced memory and low-stress levels. Furthermore, CGM+ has been shown to modulate neurotransmitter levels and promote neurogenesis. The biochemical and molecular analysis revealed that CGM+ promotes recovery following rmTBI by modulating mitochondrial bioenergetics and BDNF pathways. The findings indicate that CGM+ can be used to manage cognitive and sensory-motor defects caused by rmTBI, such as in the case of sports injuries.