Minocycline Enhance the Restorative Ability of Olfactory Ensheathing Cells by the Upregulation of BDNF and GDNF Expression After Spinal Cord Injury

Abstract

Introduction:Spinal Cord Injury (SCI) is a global public health issue that results in extensive neuronal degeneration, axonal and myelin loss, and severe functional deficits. Neurotrophic factors are a potential treatment for reducing secondary damage, promoting axon growth; they are responsible for inducing myelination after injury. Olfactory Ensheathing Cells (OECs) and minocycline have promoted locomotor function after SCI. The present study investigated the neuroprotective effects of combined treatment with minocycline and OECs on spinal cord injury related to Brain-Derived Neurotrophic Factor (BDNF) and Glial Derived Neurotrophic Factor (GDNF) expressions after SCI.Methods:Adult female rats were used to experimental SCI by weight compression method. Rats received an intraperitoneal minocycline injection (90 mg/kg) immediately after SCI and 24 h after injury. OECs were transplanted one week after the injury. The hindlimb function was assessed using Basso Beattie Bresnahan (BBB) locomotor rating scale and Electromyography (EMG). After 5 weeks, the spinal cord segment centered at the injury site was removed for histopathological analysis. Immunohistological and western blot assays were performed to observe the expression of NeuN, BDNF, GDNF, and Myelin Basic Protein (MBP).Results:SCI induced the loss of locomotor function with decreased BDNF and GDNF expressions in the injury site. Minocycline+OECs increased the score of the BBB locomotor scale and increased spared tissue in the injury site. Immunohistochemical results suggested that NeuN expression significantly increased in the minocycline+OECs group than other groups. Moreover, electromyography amplitude in treated rats was increased compared to the control group. BDNF, GDNF, and MBP expressions and the number of ventral motor neurons increased further by minocycline+OECs in SCI rats.Conclusion:The present study provides evidence that minocycline may facilitate recovery of locomotor function by OECs by increasing BDNF and GDNF expressions following SCI.HighlightsCombined treatment with Minocycline and OECs increased the locomotor function.The results showed that BDNF and GDNF expression increased by combined treatment with minocycline and OECs.Plain Language SummaryThis study examined the effect of combined treatment with minocycline and olfactory ensheathing cell on the BDNF and GDNF expression after spinal cord injury model in rat. The results showed that injection of minocycline before transplantation of OECs enhances expression of neurotrophic factors that lead to an appropriate environment for transplanted OECs and increases neuronal survival that promotes tissue sparing and functional recovery.