Postinjury Carnosine Treatment Prevents Neurotrophic Factor Decline in Denervated Muscle and Spinal Cord After...

Local intraspinal or intramuscular administration of brain-derived or glial cell line-derived neurotrophic factors (BDNF, GDNF) is known to protect neural tissue after traumatic spinal cord injury (SCI). In this study, we investigated whether oral supplementation with antioxidant carnosine, a natural dipeptide, could stimulate endogenous production of these neuroprotective molecules within the neural and muscle microenvironment 6 weeks after SCI. We assessed the effects of 6-week carnosine treatment in female Zucker rats, administered either before (CB-I) or after injury (CA-I). The impact of thoracic SCI and carnosine treatment was evaluated in in/active microenvironments of fore limb and hind limb muscles, along with their corresponding innervation regions. To better understand how carnosine treatment affects the neural microenvironment, we analysed mRNA expression levels of neurotrophic factors and their receptors. We also examined molecules that may indicate which cell types are involved in producing or responding to BDNF or GDNF in the spinal cord. Six weeks after thoracic SCI, we observed better locomotor recovery in CA-I compared to CB-I treated rats. In the hind limb, posttraumatic carnosine treatment prevented SCI-induced reductions in BDNF and GDNF protein levels. Additionally, this treatment blocked the SCI-induced reduction of GDNF protein levels and the oligodendrocyte-specific gene Olig2 in the lumbar and cervical spinal cord segments. Interestingly, the postinjury treatment elevated the gene expression in BDNF receptor- and astrocyte-specific genes in the cervical segments. The finding that carnosine may prevent BDNF and GDNF declines in denervated hind limb muscles positions this dipeptide as a promising candidate for inclusion in future combination therapies.