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

Purpose: Spinal cord injury is a global public health issue that results in extensive neuronal degeneration, axonal and myelin loss and severe functional deficits. Neurotrophic factors are potential treatment for reducing secondary damage, promoting axon growth, and are responsible for inducing myelination after injury. Olfactory ensheathing cells (OECs) and minocycline have been shown to promote locomotor function after spinal cord injury. In the present study, we investigated the neuroprotective effects of combined treatment with minocycline and OECs on the spinal cord injury in relation with 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 intraperitoneal injection of minocycline (90 mg/kg) immediately after SCI and then 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 five weeks, the segment of the spinal cord 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 loss of locomotor function with decreased BDNF and GDNF expressions in the injury site. Minocycline +OECs  increased the score of BBB locomotor scale and increased spared tissue in the injury site. Immunohistochemical results showed NeuN expression significantly increased in minocycline + OECs group than other groups. Also electromyography amplitude in treated rats was increased compared to 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 the evidence that minocycline may facilitate recovery of locomotor function by OECs through increasing of BDNF and GDNF expressions following SCI.