Zhengchao Gao

Conditioned medium of olfactory ensheathing cells promotes the functional recovery and axonal regeneration after contusive spinal cord injury.

OBJECTIVE To investigate the effectiveness and the potential role of olfactory ensheathing cell conditioned medium (OEC-M) to treat contusive spinal cord injury (SCI). METHODS The contusive SCI model was established by NYU weight-drop impactor at T10 segment. Male Sprague-Dawley rats received intraperitoneal injection of control medium (Con-M, n=18), low dose OEC-M (n=18) and high dose OEC-M (n=18). Immunofluorescence was performed to identify the purity of cultured OECs. BBB score was used to assess the functional recovery. BDNF concentrations of OEC-M, Con-M and rats plasma samples were determined by ELISA. Conventional MRI and diffusion tensor tractography (DTT) were applied to visualize the repair process of SCI. Diffusion tensor imaging (DTI) and immunohistochemistry of NF200 were carried out to evaluate the axonal regeneration. RESULTS After the systemic delivery of treatment, BBB scores and BDNF levels in peripheral blood were significantly higher in OEC-M treated groups than in Con-M group. MRI and DTT demonstrated a better radiological recovery after SCI in OEC-M treated groups and higher dose of OEC-M were accompanied with better outcomes. DTI and NF200 staining revealed the OEC-M treatment promoted axonal regeneration around the injury epicenter but no axonal regeneration was observed at the lesion site. CONCLUSION The results indicate that the OEC-M treatment improves the functional recovery and promotes the axonal regeneration around the injury epicenter after contusive SCI. This strategy represents a novel cell-free OEC based therapy to effectively treat SCI.

Metformin Protects Against Spinal Cord Injury by Regulating Autophagy via the mTOR Signaling Pathway

Spinal cord injury (SCI) is a serious central trauma, leading to severe dysfunction of motor and sensory systems. Secondary injuries, such as apoptosis and cell autophagy, significantly impact the motor function recovery process. Metformin is a widely used oral anti-diabetic agent for type 2 diabetes in the world. It has been demonstrated to promote autophagy and inhibit apoptosis in the nervous system. However, its role in recovery following SCI is still unknown. In this study, we determined that motor function, assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor assessment scale, was significantly higher in rats treated with metformin following injury. Nissl staining revealed that metformin also increased the number of surviving neurons in the spinal cord lesion. Western blot and immunofluorescent analysis revealed that mammalian target of rapamycin (mTOR) and P70S6 kinase (P70S6K) decreased, while the expression of autophagy markers increased and apoptosis markers declined in animals treated with metformin following SCI. Taken together, these findings suggest that metformin functions as a neuroprotective agent following SCI by promoting autophagy and inhibiting apoptosis by regulating the mTOR/P70S6K signaling pathway.

Feasibility of Diffusion Tensor Imaging for Assessing Functional Recovery in Rats with Olfactory Ensheathing Cell Transplantation After Contusive Spinal Cord Injury (SCI)

Background Olfactory ensheathing cell transplantation is a promising treatment for spinal cord injury. Diffusion tensor imaging has been applied to assess various kinds of spinal cord injury. However, it has rarely been used to evaluate the beneficial effects of olfactory ensheathing cell transplantation. This study aimed to explore the feasibility of diffusion tensor imaging in the evaluation of functional recovery in rats with olfactory ensheathing cell transplantation after contusive spinal cord injury. Material/Methods Immunofluorescence staining was performed to determine the purity of olfactory ensheathing cells. Rats received cell transplantation at week 1 after injury. Basso, Beattie, and Bresnahan score was used to assess the functional recovery. Magnetic resonance imaging was applied weekly, including diffusion tensor imaging. Diffusion tensor tractography was reconstructed to visualize the repair process. Results The results showed that olfactory ensheathing cell transplantation increased the functional and histological recovery and restrained the secondary injury process after the initial spinal cord injury. The fractional anisotropy values in rats with cell transplantation were significantly higher than those in the control group, while the apparent diffusion coefficient values were significantly lower. Basso, Beattie, and Bresnahan score was positively and linearly correlated with fractional anisotropy value, and it was negatively and linearly correlated with apparent diffusion coefficient value. Conclusions These findings suggest that diffusion tensor imaging parameters are sensitive biomarker indices for olfactory ensheathing cell transplantation interventions, and diffusion tensor imaging scan can reflect the functional recovery promoted by the olfactory ensheathing cell transplantation after contusive spinal cord injury.