Tetramethylpyrazine-loaded electroconductive hydrogels promote tissue repair after spinal cord injury by protecting the blood-spinal cord barrier and neurons.

Spinal cord injury (SCI) usually induces profound microvascular dysfunction. It disrupts the integrity of the blood-spinal cord barrier (BSCB), which could trigger a cascade of secondary pathological events that manifest as neuronal apoptosis and axonal demyelination. These events can further lead to irreversible neurological impairments. Thus, reducing the permeability of the BSCB and maintaining its substructural integrity are essential to promote neuronal survival following SCI. Tetramethylpyrazine (TMP) has emerged as a potential protective agent for treating the BSCB after SCI. However, its therapeutic potential is hindered by challenges in the administration route and suboptimal bioavailability, leading to attenuated clinical outcomes. To address this challenge, traditional Chinese medicine, TMP, was used in this study to construct a drug-loaded electroconductive hydrogel for synergistic treatment of SCI. A conductive hydrogel combined with TMP demonstrates good electrical and mechanical properties as well as superior biocompatibility. Furthermore, it also facilitates sustained local release of TMP at the implantation site. Furthermore, the TMP-loaded electroconductive hydrogel could suppress oxidative stress responses, thereby diminishing endothelial cell apoptosis and the breakdown of tight junction proteins. This concerted action repairs BSCB integrity. Concurrently, myelin-associated axons and neurons are protected against death, which meaningfully restore neurological functions post spinal cord injury. Hence, these findings indicate that combining the electroconductive hydrogel with TMP presents a promising avenue for potentiating drug efficacy and synergistic repair following SCI.

Temporal profiling and validation of oxidative stress-related genes in spinal cord injury.

Oxidative stress (OS) plays a pivotal role in the pathogenesis of spinal cord injury (SCI), yet its underlying mechanisms remain elusive. In this study, we explored the OS phenotype in a rat model of SCI. Subsequently, comprehensive bioinformatic analyses were conducted on microarray data pertaining to SCI (GSE45006). Notably, KEGG enrichment analysis revealed a pronounced enrichment of pivotal pathways, namely MAPK, FoxO, Apoptosis, NF-κB, TNF, HIF-1, and Chemokine across distinct phases of SCI. Furthermore, GO enrichment analysis highlighted the significance of biological processes including response to hypoxia, response to decrease oxygen levels, response to reactive oxygen species, cellular response to oxidative stress, reactive oxygen species metabolic process, and regulation of neuron death in the context of OS following SCI. Notably, our study underscores the prominence of nine genes, namely Itgb1, Itgam, Fn1, Icam1, Cd44, Cxcr4, Ptprc, Tlr4, and Tlr2 as OS key genes in SCI, consistently expressed in both the acute phase (1, 3, 7 days) and sub-acute phase (14 days). Subsequently, the relative mRNA expression of these key genes in different time points (1, 3, 7, 14 days) post-SCI. Finally, leveraging the DsigDB database, we predicted ten potential compounds potentially targeting OS and facilitating the repair of SCI, thus providing novel insights into the mechanisms underlying OS and identifying potential therapeutic targets for SCI.

Granulocyte colony-stimulating factor effects on neurological and motor function in animals with spinal cord injury: a systematic review and meta-analysis.

Background: Spinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury. Objective: To investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI. Methods: We searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria. Results: Results revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35 days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92-2.87, p < 0.00001, I2 = 69%]; inclined plane test score; electrophysiologic exam; quantitative analysis of TUNEL-positive cell numbers; quantitative analysis of GFAP immunostaining images in animal models of SCI. Subgroup analysis revealed that treatment with normal saline, phosphate-buffered saline, and no treatment resulted in significantly different neurological function effectiveness compared to the G-CSF therapy. SD rats and Wistar rats with SCI resulted in significant neurological function effectiveness. C57BL/6 mice showed no difference in the final effect. The T9-T10 or T10 segment injury model and the T8-T9 or T9 segment injury model resulted in significant neurological function effectiveness. The BBB score data showed no clear funnel plot asymmetry. We found no bias in the analysis result (Egger's test, p = 0.42). In our network meta-analysis, the SUCRA ranking showed that 15 mg/kg-20 mg/kg was an optimal dose for long-term efficacy. Conclusion: Our meta-analysis suggests that G-CSF therapy may enhance the recovery of motor activity and have a specific neuroprotective effect in SCI animal models.Systematic review registration: PROSPERO, identifier: CRD42023388315.

[Advances on selective posterior rhizotomy for lower limb function in patients with cerebral palsy].

Cerebral palsy is a common clinical syndrome of neurological disability in childhood, which seriously affects the quality of life of children and their families, and brings a heavy economic burden to the society. Domestic and foreign scholars had a long history of the application of selective posterior rhizotomy for the treatment of spastic cerebral palsy or mixed cerebral palsy with limb paralysis. It is effective in improving the lower extremity spasm of patients with cerebral palsy, and there are few cases with recurrences. After rehabilitation therapy, the muscle strength of patients with cerebral palsy was significantly improved compared with the previous one. The range of motion was significantly improved after operation, and there is no rebounded in aspect of joint activety in the long-term follow-up. The overall gait of the patient was significant improved. The author thought that selective posterior rhizotomy is effective in improving the motor function of lower limbs in patients with cerebral palsy, and it is worth being spread. However, it has to follow the principle of selecting appropriate cases before surgery, precise operation during operation, and timely and effective rehabilitation treatment after surgery, in order to achieve a better curative effect.