Background: Spinal cord injury (SCI) causes devastating neurological damage, including secondary injuries dominated by neuroinflammation. The role of Apelin, an endogenous ligand that binds the G protein-coupled receptor angiotensin-like receptor 1, in SCI remains unclear. Thus, our aim was to investigate the effects of Apelin in inflammatory responses and activation of endogenous neural stem cells (NSCs) after SCI. Methods: Apelin expression was detected in normal and injured rats, and roles of Apelin in primary NSCs were examined. In addition, we used induced pluripotent stem cells (iPSCs) as a carrier to prolong the effective duration of Apelin and evaluate its effects in a rat model of SCI. Results: Co-immunofluorescence staining suggested that Apelin was expressed in both astrocytes, neurons and microglia. Following SCI, Apelin expression decreased from 1 to 14 d and re-upregulated at 28 d. In vitro, Apelin promoted NSCs proliferation and differentiation into neurons. In vivo, lentiviral-transfected iPSCs were used as a carrier to prolong the effective duration of Apelin. Transplantation of transfected iPSCs in situ immediately after SCI reduced polarization of M1 microglia and A1 astrocytes, facilitated recovery of motor function, and promoted the proliferation and differentiation of endogenous NSCs in rats. Conclusion: Apelin alleviated neuroinflammation and promoted the proliferation and differentiation of endogenous NSCs after SCI, suggesting that it might be a promising target for treatment of SCI.

Apelin, an endogenous ligand of G protein-coupled receptor APJ, is widely distributed in the central nervous system (CNS). It can be divided into such subtypes as Apelin-13, Apelin-17, and Apelin-36 as they have different amino acid structures. All Apelin is widely studied as an adipokine, showing a significant protective effect through regulating apoptosis, autophagy, oxidative stress, angiogenesis, inflammation, and other pathophysiological processes. As an adipokine, Apelin has been found to play a crucial role in cardiovascular disease development. In this paper, we reviewed the effects and mechanisms of Apelin in treating CNS diseases, such as neurotrauma, stroke, spinal cord injury, primary tumors, neurodegenerative diseases, psychiatric diseases, epilepsy, and pain.

Introduction: Serum response factor (SRF) is important in muscle development, tissue repair, and neuronal regulation. Objectives: This research aims to thoroughly examine the effects of SRF on spinal cord injury (SCI) and its ability to significantly impact the recovery and regeneration of neuronal axons. Methods: The researchers created rat models of SCI and scratch injury to primary spinal cord neurons to observe the expression of relevant factors after neuronal injury. Results: We found that the SRF, Ras, Raf, and cofilin levels increased after injury and gradually returned to normal levels. Afterward, researchers gave rats with SCI an SRF inhibitor (CCG1423) and studied the effects with nuclear magnetic resonance and transmission electron microscopy. The SRF inhibitor rodents had worse spinal cord recovery and axon regrowth than the control group. And the apoptosis of primary neurons after scratch injury was significantly higher in the SRF inhibitor group. Additionally, the researchers utilized lentiviral transfection to modify the SRF expression in neurons. SRF overexpression increased neuron migration while silencing SRF decreased it. Finally, Western blotting and RT‐PCR were conducted to examine the expression changes of related factors upon altering SRF expression. The results revealed SRF overexpression increased Ras, Raf, and cofilin expression. Silencing SRF decreased Ras, Raf, and Cofilin expression. Conclusion: Based on our research, the SRF promotes axonal regeneration by activating the “Ras–Raf‐Cofilin” signaling pathway.

Spinal cord injury (SCI) is a severe neurological disorder characterized by axonal damage, myelin destruction, and motor and sensory dysfunction. This study employed mass spectrometry-based proteomic analysis to systematically identify differentially expressed proteins (DEPs) between sham-operated and SCI rats at post-injury time points (1, 3, 7, 14, and 28 days). 3-Hydroxy-3-methylglutaryl-CoA synthase 1 (HMG-CoA synthase 1, Hmgcs1) was identified as a key candidate protein. To investigate the role of Hmgcs1 in SCI repair, we utilized viral vector technology for functional studies both in vivo and in an in vitro co-culture system. Finally, RNA sequencing (RNA-seq) and quantitative reverse-transcription PCR (qRT-PCR) were integrated to elucidate Hmgcs1-mediated signaling pathways by validating downstream target gene expression. The results demonstrated that Hmgcs1 overexpression enhanced cholesterol synthesis in astrocytes post-injury, effectively promoted neuronal myelin repair, axonal regeneration, and improved motor functional recovery in rats. Notably, neuropilin-1 (Nrp1) expression exhibited Hmgcs1-dependent regulation.