Olfactory ensheathing cell transplantation alters the expression of chondroitin sulfate proteoglycans and promotes axonal regeneration after spinal cord injury

Cell transplantation is a potential treatment for spinal cord injury. Olfactory ensheathing cells(OECs) play an active role in the repair of spinal cord injury as a result of the dual characteristics of astrocytes and Schwann cells. However, the specific mechanisms of repair remain poorly understood. In the present study, a rat model of spinal cord injury was established by transection of T10. OECs were injected into the site, 1 mm from the spinal cord stump. To a certain extent, OEC transplantation restored locomotor function in the hindlimbs of rats with spinal cord injury, but had no effect on the formation or volume of glial scars. In addition, OEC transplantation reduced the immunopositivity of chondroitin sulfate proteoglycans(neural/glial antigen 2 and neurocan) and glial fibrillary acidic protein at the injury site, and increased the immunopositivity of growth-associated protein 43 and neurofilament. These findings suggest that OEC transplantation can regulate the expression of chondroitin sulfate proteoglycans in the spinal cord, inhibit scar formation caused by the excessive proliferation of glial cells, and increase the numbers of regenerated nerve fibers, thus promoting axonal regeneration after spinal cord injury. The study was approved by the Animal Ethics Committee of the Medical College of Xi'an Jiaotong University, China(approval No. 2018-2048) on September 9, 2018.

Feasibility of 3.0 T diffusion-weighted nuclear magnetic resonance imaging in the evaluation of functional recovery of rats with complete spinal cord injury

Diffusion tensor imaging is a sensitive way to reflect axonal necrosis and degeneration, glial cell regeneration and demyelination following spinal cord injury, and to display microstructure changes in the spinal cord in vivo. Diffusion tensor imaging technology is a sensitive method to diagnose spinal cord injury; fiber tractography visualizes the white matter fibers, and directly displays the structural integrity and resultant damage of the fiber bundle. At present, diffusion tensor imaging is restricted to brain examinations, and is rarely applied in the evaluation of spinal cord injury. This study aimed to explore the fractional anisotropy and apparent diffusion coefficient of diffusion tensor magnetic resonance imaging and the feasibility of diffusion tensor tractography in the evaluation of complete spinal cord injury in rats. The results showed that the average combined scores were obviously decreased after spinal cord transection in rats, and then began to increase over time. The fractional anisotropy scores after spinal cord transection in rats were significantly lower than those in normal rats （P 〈 0.05）; the apparent diffusion coefficient was significantly increased compared with the normal group （P 〈 0.05）. Following spinal cord transection, fractional anisotropy scores were negatively correlated with apparent diffusion coefficient values （r = -0.856, P 〈 0.01）, and positively correlated with the average combined scores （r = 0.943, P 〈 0.01）, while apparent diffusion coefficient values had a negative correlation with the average combined scores （r = -0.949, P 〈 0.01）. Experimental findings suggest that, as a non-invasive examination, diffusion tensor magnetic resonance imaging can provide qualita- tive and quantitative information about spinal cord injury. The fractional anisotropy score and apparent diffusion coefficient have a good correlation with the average combined scores, which reflect functional recovery after spinal cord injury.

Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy

Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury（SCI）; however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the autophagy inhibitor 3-methyladenine（3-MA） in a rat model of SCI. The rats were randomly assigned to the SCI, lithium, 3-MA and sham groups. In the 3-MA group, rats were intraperitoneally injected with 3-MA（3 mg/kg） 2 hours before SCI. In the lithium and 3-MA groups, rats were intraperitoneally injected with lithium（LiCl; 30 mg/kg） 6 hours after SCI and thereafter once daily until sacrifice. At 2, 3 and 4 weeks after SCI, neurological function and diffusion tensor imaging indicators were remarkably improved in the lithium group compared with the SCI and 3-MA groups. The Basso, Beattie and Bresnahan locomotor rating scale score and fractional anisotropy values were increased, and the apparent diffusion coefficient value was decreased. Immunohistochemical staining showed that immunoreactivities for Beclin-1 and light-chain 3 B peaked 1 day after SCI in the lithium and SCI groups. Immunoreactivities for Beclin-1 and light-chain 3 B were weaker in the 3-MA group than in the SCI group, indicating that 3-MA inhibits lithium-induced autophagy. Furthermore, NeuN＋ neurons were more numerous in the lithium group than in the SCI and 3-MA groups, with the fewest in the latter. Our findings show that lithium reduces neuronal damage after acute SCI and promotes neurological recovery by inducing autophagy. The neuroprotective mechanism of action may not be entirely dependent on the enhancement of autophagy, and furthermore, 3-MA might not completely inhibit all autophagy pathways.

Lithium promotes recovery after spinal cord injury

Lithium is associated with oxidative stress and apoptosis,but the mechanism by which lithium protects against spinal cord injury remains poorly understood.In this study,we found that intraperitoneal administration of lithium chloride(LiCl)in a rat model of spinal cord injury alleviated pathological spinal cord injury and inhibited expression of tumor necrosis factorα,interleukin-6,and interleukin 1β.Lithium inhibited pyroptosis and reduced inflammation by inhibiting Caspase-1 expression,reducing the oxidative stress response,and inhibiting activation of the Nod-like receptor protein 3 inflammasome.We also investigated the neuroprotective effects of lithium intervention on oxygen/glucose-deprived PC12 cells.We found that lithium reduced inflammation,oxidative damage,apoptosis,and necrosis and up-regulated nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1 in PC12 cells.All-trans retinoic acid,an Nrf2 inhibitor,reversed the effects of lithium.These results suggest that lithium exerts anti-inflammatory,anti-oxidant,and anti-pyroptotic effects through the Nrf2/heme oxygenase-1 pathway to promote recovery after spinal cord injury.This study was approved by the Animal Ethics Committee of Xi’an Jiaotong University(approval No.2018-2053)on October 23,2018.

The Surgical Approaches of Cervical Spondylotic Myelopathy and the Predictive Factors for the Surgical Outcomes

Objective To explore the efficacy and safety of different surgical approaches of cervical spondylotic myelopathy, and the predictive factors for the outcome of surgery. Methods Clinical data of 68 consecutive patients who underwent surgical treatment from 2003-08-01 to 2006-12-01 were collected. The quantization of the efficacy of operation was made by applying Japanese Orthopedic Association (JOA) scoring system, based on which the recovery rate and satisfaction rate were calculated. In the patients who underwent anterior approach, we compared the recovery rate among the subgroups of different duration of symptoms, age at surgery and the severity of diseases. Any surgery-related complications were also noted. Results 73.5% (50/68) patients underwent anterior approach, with an average recovery rate of (68.21 ± 10.06)% and the satisfaction rate of 88.00%;20.6% patients (14/68) underwent posterior approach, with an average recovery rate of (64.03 ± 7.07)% and the satisfaction rate of 100%. The recovery rate had no significant difference in the two approaches. Only 4 patients (5.9%) underwent anterior and posterior combined approach, and the recovery rate and the satisfaction rate were 65.10% and 100%, respectively. In the group of patients who accepted anterior approach, no significant differences were found in the recovery rates of different age subgroups and different duration of symptom subgroups;the significant differences recovery rates between the moderate and severe subgroups were identified. Minor complications, such as asymptomatic screw misplacement, transient dysphagia/odynophagia, pain related to the donor site and axial syndrome, were observed in a few patients. Conclusion The JOA score can be improved by applying the appropriate approaches and the high recovery and satisfaction rates can be achieved at the same time. The efficacies of anterior and posterior approaches were similar. The complications of surgery were minor. In the patients who underwent anterior approach, the severity of diseases was a predictive factor for the outcome of surgery.

Increased function of the TRPV1 channel in small sensory neurons after local inflammation or in vitro exposure to the pro-inflammatory cytokine GRO/KC

Objective Inflammation at the level of the sensory dorsal root ganglia （DRGs） leads to robust mechanical pain behavior and the local inflammation has direct excitatory effects on sensory neurons including small, primarily no- ciceptive, neurons. These neurons express the transient receptor potential vanilloid-1 （TRPV1） channel, which integrates multiple signals of pain and inflammation. The aim of this study was to characterize the regulation of the TRPV1 channel by local DR（] inflammation and by growth-related oncogene （（]RO/KC, systemic name： CXCL1）, a cytokine known to be upregulated in inflamed DRGs. Methods Activation of the TRPV1 receptor with capsaicin was studied with patch clamp methods in acutely isolated small-diameter rat sensory neurons in primary culture. In vivo, behavioral effects of TRPVI and GRO/KC were examined by paw injections. Results Neurons isolated from lumbar DRGs 3 days after local inflammation showed enhanced TRPV1 function： tachyphylaxis （the decline in response to repeated applications of capsaicin） was significantly reduced. A similar effect on tachyphylaxis was observed in neurons pre-treated for 4 h in vitro with GRO/KC. This effect was blocked by H-89, a protein kinase A inhibitor. Consistent with the in vitro results, in vivo behavioral responses to paw injection of capsaicin were enhanced and prolonged by pre-injecting the paw with GRO/KC 4 h before the capsaicin injection. GRO/KC paw injections alone did not elicit pain behaviors. Conclusion Function of the TRPV1 channel is enhanced by DRG inflammation and these effects are preserved in vitro during short-term culture. The effects （decreased tachyphylaxis） are mimicked by incubation with GRO/KC, which has previously been found to be strongly upregulated in this and other pain models.