Recovery from spinal cord injury (SCI) remains an unsolved problem. As a major component of SCI lesion, the glial scar which is primarily composed by scar-forming astrocytes plays important roles in spinal cord regeneration. By reviewing recent studies on the glial scar and scar-forming astrocytes, we briefly discuss glial scar formation and the components of the glial scar. Then, we analyze the dual role of the glial scar in a dynamic perspective, especially focus on the scar-forming astrocytes, to explain the seemingly contradictory findings supporting the beneficial and inhibitory effects of them. Finally, we provide several pieces of advice and remarks on novel therapeutic strategies targeting the glial scar and scar-forming astrocytes.

In the central nervous system (CNS), astrocytes form networks interconnected by gap junctions made from connexins of the subtypes Cx30 and Cx43. When unopposed by an adjoining hemichannel, astrocytic connexins can act as hemichannels to control the release of small molecules such as ATP and glutamate into the extracellular space. Accruing evidence indicates that astrocytic connexins are crucial for the coordination and maintenance of physiologic CNS activity. Here we provide an update on the role of astrocytic connexins in neurodegenerative disorders, glioma, and ischemia. In addition, we address the regulation of Cx43 in chronic pain.

Background: Due to the increasing number of patients with bone defects, bone nonunion and osteomyelitis, tumor and congenital diseases, bone repair has become an urgent problem to be solved. Methods: In this study, the 3D-printed scaffolds of ternary composites containing mesoporous bioglass fibers of magnesium calcium silicate (mMCS), gliadin (GA) and polycaprolactone (PCL) were fabricated using a 3D Bioprinter. Results: The compressive strength and in vitro degradability of the mMCS/GA/PCL composites (MGPC) scaffolds were improved with the increase of mMCS content. In addition, the attachment and proliferation of MC3T3-E1 cells on the scaffolds were significantly promoted with the increase of mMCS content. Moreover, the cells with normal phenotype attached and spread well on the scaffolds surfaces, indicating good cytocompatibility. The scaffolds were implanted into the femur defects of rabbits, and the results demonstrated that the scaffold containing mMCS stimulated new bone formation and ingrowth into the scaffolds through scaffolds degradation in vivo. Moreover, the expression of type I collagen into scaffolds was enhanced with the increase of mMCS content. Conclusion: The 3D-printed MGPC scaffold with controllable architecture, good biocompatibility, high compressive strength, proper degradability and excellent in vivo osteogenesis has great potential for bone regeneration.

Background: Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear.Results: SPP1 and PKCα were found upregulated after human median peripheral nerve injury, which promoted SCs proliferation and survival. The promoted proliferation and inhibited apoptosis by SPP1 were blocked after the treatment of PKCα antagonist Gö6976. Whereas, the inhibited proliferation and enhanced apoptosis induced by silence of SPP1 could be rescued by the activation of PKCα, which suggested that SPP1 functioned through PKCα. Moreover, both CD44 and αvβ3 were found expressed in SCs and increased after peripheral nerve injury. Silence of CD44 or β3 alleviated the increased proliferation and inhibited apoptosis induced by recombinant osteopontin, suggesting the function of SPP1 on SCs were dependent on CD44 and β3.Conclusion: These results suggested that SPP1 promoted proliferation and inhibited apoptosis of SCs through PKCα signaling pathway by binding with CD44 and αvβ3. This study provides a potential therapeutic target for improving peripheral nerve recovery.

Neuropathic pain is usually caused by injury or dysfunction of the somatosensory system, and medicine is a common way of treatment. Currently, there are still no satisfactory drugs, like opioids and lidocaine, which carry a high risk of addiction. Protein tyrosine phosphatase receptor type D (PTPRD) is a known therapeutic target in addiction pathways and small molecule inhibitors targeting it, such as 7-butoxy illudalic acid analog (7-BIA), have recently been developed to tackle addition. PTPRD is also upregulated in the dorsal root ganglion (DRG) in a rat model of neuropathic pain, but is not yet clear whether PTPRD contributes to the development of neuropathic pain. Here, we established a chronic constriction injury (CCI) and evaluated PTPRD expression and its association with neuropathic pain. PTPRD expression was found to gradually increase after CCI in DRGs, and its expression was concomitant with the progressive development of hypersensitivity as assessed by both mechanical and thermal stimuli. Both PTPRD knockdown and administration of PTPRD inhibitor 7-BIA alleviated CCI-induced neuropathic pain while upregulating STING and IFN-α in the DRG. Treatment with H-151, a STING inhibitor, abolished the analgesic effects of PTPRD knockdown. Taken together, our study suggests that increased levels of PTPRD in the DRG following CCI are involved in the development of neuropathic pain via the STING-IFN-I pathway. 7-BIA, a small molecule inhibitor of PTPRD with anti-addiction effects, may represent a novel and safe therapeutic strategy for the clinical management of neuropathic pain without the risk of addiction.

After spinal cord injury (SCI), the irreversible loss of neurons and the dense glial scar are two of the leading causes of axon regeneration failure. The adult mammalian spinal cord lacks the ability to spontaneously produce new neurons, making it a key challenge to provide new neurons for spinal cord regeneration. Additionally, the dual role of the glial scar (both inhibitory and protective) makes it difficult to manipulate it for therapeutic purposes. In this study, using a single transcription factor Sry‐related HMG‐box 2 (Sox2) delivered by adeno‐associated virus (AAV), we reprogrammed some of the astrocytes targeted by the viral vectors in the glial scar into neurons in a severe SCI model. We show that this astrocytic reprogramming alone can propel axon regeneration by not only replenishing the lost neurons, but also moderately reducing the density of the glial scar without interrupting its integrity. Beyond that, astrocytic reprogramming can significantly improve functional recovery when combined with running wheel rehabilitation, which provides use‐dependent plasticity. These findings may provide us with a new idea for how to manipulate the glial scar and a promising therapeutic strategy that combines biological intervention with a rehabilitation strategy.