Single-Cell Sequencing Technology and Its Application in the Study of Central Nervous System Diseases.

The mammalian central nervous system consists of a large number of cells, which contain not only different types of neurons, but also a large number of glial cells, such as astrocytes, oligodendrocytes, and microglia. These cells are capable of performing highly refined electrophysiological activities and providing the brain with functions such as nutritional support, information transmission and pathogen defense. The diversity of cell types and individual differences between cells have brought inspiration to the study of the mechanism of central nervous system diseases. In order to explore the role of different cells, a new technology, single-cell sequencing technology has emerged to perform specific analysis of high-throughput cell populations, and has been continuously developed. Single-cell sequencing technology can accurately analyze single-cell expression in mixed-cell populations and collect cells from different spatial locations, time stages and types. By using single-cell sequencing technology to compare gene expression profiles of normal and diseased cells, it is possible to discover cell subsets associated with specific diseases and their associated genes. Therefore, scientists can understand the development process, related functions and disease state of the nervous system from an unprecedented depth. In conclusion, single-cell sequencing technology provides a powerful technology for the discovery of novel therapeutic targets for central nervous system diseases.

Effects and mechanisms of salidroside on the behavior of SPS-induced PTSD rats.

Post-traumatic stress disorder (PTSD) is a complex mental disorder, closely associated with stress and traumatic events. Salidroside (Sal) has been reported to possess neuroprotective effects. However, the behavioral effects and mechanisms of Sal on PTSD remain unknown. In this study, we utilized a rat model of PTSD induced by single prolonged stress (SPS) and administered Sal intraperitoneally (25, 50, 75 mg/kg/d) for 14 days. We then examined the behavioral effects and underlying mechanisms of Sal on SPS-induced PTSD rats. Our findings demonstrated that Sal alleviated anxiety-like behavior and spatial learning and memory impairment in SPS-induced PTSD rats. Furthermore, Sal treatment preserved the histomorphology of the hippocampal region. It was observed that Sal protected against hippocampal neuronal apoptosis in PTSD rats by reducing the number of TUNEL-positive cells and modulating apoptosis-related proteins (Bcl-2 and Bax). Additionally, Sal inhibited the activation of the NF-κB/iNOS/COX-2 signaling pathway in the hippocampus of PTSD rats, thereby suppressing the release of inflammatory factors (TNF-α and IL-1ß) and the activation of microglia. Notably, Sal increased the expression of synapse-associated proteins PSD95 and Synapsin I in the hippocampus, while also enhancing dendritic density in the region. In conclusion, our results demonstrated that Sal could attenuate SPS-induced PTSD-like behaviors by inhibiting hippocampal neuronal apoptosis, enhancing hippocampal synaptic plasticity, and reducing neuroinflammatory responses. These findings may provide a foundation for the potential clinical application of Sal in the treatment of PTSD.

Effects and mechanisms of tanshinone IIA on PTSD-like symptoms.

BACKGROUND: In recent years, Salvia miltiorrhiza and its active substances have remarkably progressed in treating central neurological disorders. Tanshinone IIA (TSA) is an active ingredient derived from the rhizome of Salvia miltiorrhiza that has been found to alleviate the symptoms of several psychiatric illnesses. Post-traumatic stress disorder (PTSD) is a mental disorder that results after experiencing a serious physical or psychological injury. The currently used drugs are not satisfactory for the treatment of PTSD. However, it has been reported that TSA can improve PTSD-like symptoms like learning and memory, cognitive disorder, and depression through multi-target regulation. PURPOSE: This paper discusses the ameliorative effects of TSA on PTSD-like symptoms and the possible mechanisms of action in terms of inhibition of neuronal apoptosis, anti-neuroinflammation, and anti-oxidative stress. Based on the pathological changes and clinical observations of PTSD, we hope to provide some reference for the clinical transformation of Chinese medicine in treating PTSD. METHODS: A large number of literatures on tanshinone in the treatment of neurological diseases and PTSD were retrieved from online electronic PubMed and Web of Science databases. CONCLUSION: TSA is a widely studied natural active ingredient against mental illness. This review will contribute to the future development of TSA as a new clinical candidate drug for improving PTSD-like symptoms.

The role of RNA splicing factor PTBP1 in neuronal development.

Alternative pre-mRNA splicing, which produces various mRNA isoforms with distinct structures and functions from a single gene, is regulated by specific RNA-binding proteins and is an essential method for regulating gene expression in mammals. Recent studies have shown that abnormal change during neuronal development triggered by splicing mis-regulation is an important feature of various neurological diseases. Polypyrimidine tract binding protein 1 (PTBP1) is a kind of RNA-binding proteins with extensive biological functions. As a well-known splicing regulator, it affects the neuronal development process through its involvement in axon formation, synaptogenesis, and neuronal apoptosis, according to the most recent studies. Here, we summarized the mechanism of alternative splicing, structure and function of PTBP1, and the latest research progress on the role of alternative splicing events regulated by PTBP1 in axon formation, synaptogenesis and neuronal apoptosis, to reveal the mechanism of PTBP1-regulated changes in neuronal development process.

Syntaphilin mediates axonal growth and synaptic changes through regulation of mitochondrial transport: a potential pharmacological target for neurodegenerative diseases.

Mitochondria are a crucial energy source for maintaining neuronal growth and synaptic function. Neurons possess unique morphological characteristics, which make the proper regulation of mitochondrial transport essential for meeting their energy demands. Syntaphilin (SNPH) is capable of specifically targeting the outer membrane of axonal mitochondria, anchoring them to microtubules, and thereby preventing their transport. SNPH also interacts with other mitochondrial proteins to regulate mitochondrial transport. The regulation of mitochondrial transport and anchoring mediated by SNPH is indispensable for axonal growth during neuronal development, maintenance of ATP levels during neuronal synaptic activity, and regeneration of mature neurons following damage. Precise blocking of SNPH may be an effective therapeutic strategy for neurodegenerative diseases and related mental disorders.

Effects and mechanisms of extremely cold environment on body response after trauma.

With the outbreak of the Ukrainian crisis, extremely cold environment warfare has once again become the focus of international attention. People exposed to extremely cold environments may suffer from cold damage, further aggravate trauma, trigger high disability and mortality rates, and even cause serious sequelae. To declare the effects and mechanisms of the extremely cold environment on the body after trauma, this paper reviews, firstly, physiological reaction of human body in an extremely cold environment. Then, the post-traumatic body response in an extremely cold environment was introduced, and finally, the sequelae of trauma in extremely cold environment was further summarized in the paper. The results indicated that extremely cold environment can cause a series of damage to the body, especially the body after trauma. The extremely cold factor is a double-edged sword, showing a favorable and unfavorable side in different aspects. Moreover, in addition to the trauma suffered by the body, the subsequent sequelae such as cognitive dysfunction, anxiety, depression and even post-traumatic stress disorder may also be induced. The paper summarizes the human body's physiological response in an extremely cold environment, and declares the effects and mechanisms of the extremely cold environment on the body after trauma, which may provide a theoretical basis for effectively improving the level of combat trauma treatment in extremely cold regions.

The ameliorative effects and mechanisms of abscisic acid on learning and memory.

Abscisic acid (ABA), a conserved hormone existing in plants and animals, not only regulates blood glucose and inflammation but also has good therapeutic effects on obesity, diabetes, atherosclerosis and inflammatory diseases in animals. Studies have shown that exogenous ABA can pass the blood-brain barrier and inhibit neuroinflammation, promote neurogenesis, enhance synaptic plasticity, improve learning, memory and cognitive ability in the central nervous system. At the same time, ABA plays a crucial role in significant improvement of Alzheimer's disease, depression, and anxiety. Here we review the previous research progress of ABA on the physiological effects and clinical application in the related diseases. By summarizing the biological functions of ABA, we aim to reveal the possible mechanisms of ameliorative function of ABA on learning and memory, to provide a theoretical basis that ABA as a novel and safe drug improves learning memory and cognitive impairment in central system diseases such as aging, neurodegenerative diseases and traumatic brain injury.

The latest role of nerve-specific splicing factor PTBP1 in the transdifferentiation of glial cells into neurons.

Central nervous system injury diseases can cause the loss of many neurons, and it is difficult to regenerate. The field of regenerative medicine believes that supplementing the missing neurons may be an ideal method for nerve injury repair. Recent studies have found that down-regulation of polypyrimidine tract binding protein 1 (PTBP1) expression can make glial cells transdifferentiate into different types of neurons, which is expected to be an alternative therapy to restore neuronal function. This article summarized the research progress on the structure and biological function of the PTBP family, the mutual regulation of PTBP1 and PTBP2, their role in neurogenesis, and the latest research progress in targeting PTBP1 to mediate the transdifferentiation of glial cells into neurons, which may provide some new strategies and new ideas for the future treatment of central nervous system injury and neurodegenerative diseases. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing.

Potential of thrombospondin-1 in treatment of polycystic ovary syndrome rat model: a preliminary study.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease in reproductive women, and the endocrine levels are also affected by diseases. The aim of this study was to determine the effect of thrombospondin-1 (TSP-1) on PCOS rat model. METHODS: We established the PCOS rat model, the serum hormones including TSP-1 expression were determined and morphological characteristics were investigated to evaluate the model. These above endocrine and morphological features were investigated again to evaluate the effect of TSP-1 treatment. RESULTS: In the PCOS model group, the serum hormones change (higher luteinizing hormone, testosterone and estrogen) and decreased TSP-1 expression levels were found compared with the control group. Besides, the morphological characteristics of PCOS were also observed in the model group. After TSP-1 treatment, the higher TSP-1, ANGPT2, PDGFB and PDGFD expression levels, the lower LH and T levels, decreased vessel density as well as VEGFA and ANGPT1 expression levels were found compared with the control group, and the ovary morphological changes were also observed in the TSP-1 experimental group. CONCLUSIONS: TSP-1 delivery system might be an alternative therapy for PCOS treatment.

Chlorogenic Acid Improves PTSD-like Symptoms and Associated Mechanisms.

Chlorogenic acid (CGA) is a kind of traditional Chinese medicine, abundant in honeysuckle and eucommia, and has a wide range of biological activities, and pharmacological effects. Previous studies have shown that CGA can regulate learning, memory, cognitive ability, coupled with improvement to anxiety, depression, and other post-traumatic stress disorder (PTSD)-like symptoms. This article explores the protective effects of CGA on neurons through its anti-apoptotic effect, inhibition of neuroinflammation and oxidative stress, which may be the mechanisms of its improvement of PTSD-like symptoms. It may provide a new therapeutic strategy for the treatment of PTSD and its comorbidities.

The Effects of P75NTR on Learning Memory Mediated by Hippocampal Apoptosis and Synaptic Plasticity.

Neurological diseases bring great mental and physical torture to the patients, and have long-term and sustained negative effects on families and society. The attention to neurological diseases is increasing, and the improvement of the material level is accompanied by an increase in the demand for mental level. The p75 neurotrophin receptor (p75NTR) is a low-affinity neurotrophin receptor and involved in diverse and pleiotropic effects in the developmental and adult central nervous system (CNS). Since neurological diseases are usually accompanied by the regression of memory, the pathogenesis of p75NTR also activates and inhibits other signaling pathways, which has a serious impact on the learning and memory of patients. The results of studies shown that p75NTR is associated with LTP/LTD-induced synaptic enhancement and inhibition, suggest that p75NTR may be involved in the progression of synaptic plasticity. And its proapoptotic effect is associated with activation of proBDNF and inhibition of proNGF, and TrkA/p75NTR imbalance leads to pro-survival or proapoptotic phenomena. It can be inferred that p75NTR mediates apoptosis in the hippocampus and amygdale, which may affect learning and memory behavior. This article mainly discusses the relationship between p75NTR and learning memory and associated mechanisms, which may provide some new ideas for the treatment of neurological diseases.

Variations in the Profiles of Vascular-Related Factors Among Different Sub-Types of Polycystic Ovarian Syndrome in Northern China.

Recently, a growing body of evidence has suggested that abnormal ovarian angiogenesis, secondary to the imbalance between various angiogenic markers, is involved in the pathogenesis of PCOS, and this has led to the use of various interventions (such as Diane-35) to restore the normal ovarian angiogenesis. Therefore, we conducted the current investigation to determine the role of such markers (endothelial growth factor (VEGF), endostatin (ES), and thrombospondin-1 (TSP-1)) in the pathogenesis of PCOS along with the associated changes in ovarian blood flow in patients with PCOS compared to healthy controls, both before and after a course of oral contraception. A total of 381 patients with PCOS and 98 healthy females of childbearing age were recruited from July 2014 to June 2017 at the Reproductive Center of the Second Affiliated Hospital of Harbin Medical University. The serum levels of VEGF, ES, and TSP-1 were determined by enzyme-linked immunosorbent assay, while ovarian perfusion was measured by the pulsatility index (PI) and resistance index (RI) by using transvaginal color Doppler ultrasound. Repeated analyses were carried out after 3 months of Diane-35 treatment. Post-treatment serum levels of luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio of patients with PCOS decreased significantly (P <0.05). The RI values of most PCOS patients increased after treatment (P<0.05), while PI was significantly increased in all patients (P<0.05). However, variable changes in the serum levels of TSP-1, VEGF, and ES after treatment were observed. Serum VEGF levels showed a negative correlation with serum LH/FSH ratio, T concentration, and ES (P <0.05), while ES levels were negatively correlated with serum T concentrations only (P<0.05). The markers of angiogenesis (VEGF, ES, and TSP-1) were expressed differently among PCOS patients, who also responded differently to the same course of Diane-35 treatment. This field still warrants further investigation to reach a more definitive conclusion.

Nucleic Acid Vaccine Targeting Nogo-66 Receptor and Paired Immunoglobulin-Like Receptor B as an Immunotherapy Strategy for Spinal Cord Injury in Rats.

Nogo-66 receptor (NgR) and paired immunoglobulin-like receptor B (PirB) are two common receptors of various myelin-associated inhibitors (MAIs) and, thus, play an important role in MAIs-induced inhibitory signalling of regeneration following spinal cord injury (SCI). Based on the concept of protective autoimmunity, vaccine approaches could induce the production of antibodies against inhibitors in myelin, such as using purified myelin, spinal cord homogenates, or MAIs receptor NgR, in order to block the inhibitory effects and promote functional recovery in SCI models. However, due to the complication of the molecules and the mechanisms involved in MAIs-mediated inhibitory signalling, these immunotherapy strategies have yielded inconsistent outcomes. Therefore, we hypothesized that the choice and modification of self-antigens, and co-regulating multiple targets, may be more effective in repairing the injured spinal cord and improving functional recovery. In this study, NgR and PirB were selected to construct a double-targeted granulocyte-macrophage colony stimulating factor-NgR-PirB (GMCSF-NgR-PirB) nucleic acid vaccine, and investigate the efficacy of this immunotherapy in a spinal cord injury model in rats. The results showed that this vaccination could stimulate the production of antibodies against NgR and PirB, block the inhibitory effects mediated by various MAIs, and promote nerve regeneration and functional recovery after spinal cord injury. These findings suggest that nucleic acid vaccination against NgR and PirB can be a promising therapeutic strategy for SCI and other central nervous system diseases and injuries.

Synaptic Plasticity in PTSD and associated Comorbidities: The Function and Mechanism for Diagnostics and Therapy.

The studying of synaptic plasticity, the ability of synaptic connections between neurons to be weakened or strengthened and specifically long-term potentiation (LTP) and long-term depression (LTD), is one of the most active areas of research in neuroscience. The process of synaptic connections playing a crucial role in improving cognitive processes is important to the processing of information in brain. In general, the dysfunction of synaptic plasticity was involved in a wide spectrum of central nervous system (CNS) disorders, including some neurodegenerative disorders. Thus, synaptic plasticity which is a dysfunction reported in neurodegenerative disorders may also be involved in posttraumatic stress disorder (PTSD), an anxiety and/or memory disorder developed after experiencing natural disasters, domestic violence or combat-related trauma. In this review, we mainly focus on discussing the biological function and mechanism for diagnostics and therapy of synaptic plasticity in PTSD and associated comorbidities, such as schizophrenia, depression, sleep disturbances and alcohol dependence, and further studying the molecular mechanisms of PTSD with a particular focus on the LTP/LTD, glutamatergic ligand-receptor systems, voltage-gated calcium channels (VGCCs) and brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB). The summarized function and mechanism of synaptic plasticity in PTSD and its comorbidities may help us further understand PTSD and provide insight into novel neuroplasticity modifying for diagnostics and treatment for PTSD.

Protective effect of arctigenin on ethanol-induced neurotoxicity in PC12 cells.

As a neurotropic substance, ethanol can damage nerve cells through an increase in the production of free radicals, interference of neurotrophic factor signaling pathways, activation of endogenous apoptotic signals and other molecular mechanisms. Previous studies have revealed that a number of natural drugs extracted from plants offer protection of nerve cells from damage. Among these, arctigenin (ATG) is a lignine extracted from Arctium lappa (L.), which has been found to exert a neuroprotective effect on scopolamine­induced memory deficits in mice with Alzheimer's disease and glutamate-induced neurotoxicity in primary neurons. As a result, it may offer beneficial effects on ethanol-induced neurotoxicity. However, the effects of ATG on ethanol­induced nerve damage remain to be elucidated. To address this issue, the present study used rat pheochromocytoma PC12 cells to investigate the neuroprotective effects of ATG on ethanol-induced cell damage by performing an MTT reduction assay, cell cycle analysis, Hoechst33342/propidium iodide fluorescence staining and flow cytometry to examine apoptosis. The results showed that 10 µM ATG effectively promoted the proliferation of damaged cells, and increased the distribution ratio of the cells at the G2/M and S phases (P<0.05). In addition, the apoptosis and necrosis of the PC12 cells were significantly decreased following treatment with ATG. Therefore, it was concluded that 10 µM ATG had a protective effect on ethanol­induced injury in PC12 cells.

Beneficial effects of chlorogenic acid on alcohol-induced damage in PC12 cells.

As one of the most commonly abused psychotropic substances, ethanol exposure has deleterious effects on the central nervous system (CNS). The most detrimental results of ethanol exposure during development are the loss of neurons in brain regions such as the hippocampus and neocortex, which may be related to the apoptosis and necrosis mediated by oxidative stress. Recent studies indicated that a number of natural drugs from plants play an important role in protection of nerve cells from damage. Among these, it has been reported that chlorogenic acid (CA) has neuroprotective effects against oxidative stress. Thus, it may play some beneficial effects on ethanol-induced neurotoxicity. However, the effects of CA on ethanol-induced nerve damage remain unclear. In order to investigate the protective effects of CA on alcohol-induced apoptosis in rat pheochromocytoma PC12 cells, in the present study, cell viability and the optimal dosage of CA were first quantified by MTT assay. Then, the cell apoptosis and cell cycle were respectively investigated by Hoechst 33258 staining and flow cytometer (FCM). To further clarify the possible mechanism, followed with the test of mitochondria transmembrane potential with Rhodamine 123 (Rho 123) staining, the expression of Bcl-2, Capase-3 and growth associated protein-43 (GAP-43) were analyzed by immunofluorescence assay separately. The results showed that treatment with 500 mM alcohol decreased the cell viability and then significantly induced apoptosis in PC12 cells. However, when pretreated with different concentrations of CA (1, 5, 10, 50 µM), cell viability increased in different degree. Comparatively, CA with the concentration of 10 µM most effectively promoted the proliferation of damaged cells, increased the distribution ratio of the cells at the G2/M and S phases, and enhanced mitochondria transmembrane potential. This appears to be in agreement with up-regulation of the expression of Bcl-2 and GAP-43, and down-regulation of the expression of Capsae-3. Taken together, CA can increase cell viability and promote cell differentiation by preventing alcohol-induced cell from apoptosis. The mechanism may be related to the enhancement of the expression of GAP-43 and the inhibition of mitochondrial apoptotic pathway including promotion of mitochondria transmembrane potential, up-regulation of the expression of Bcl-2, and down-regulation of the expression of Capsae-3.

Experimental and Clinical Advances in Immunotherapy Strategies for Spinal Cord Injury Target on MAIs and Their Receptors.

In the injured adult mammalian central nervous system (CNS), the failure of axonal regeneration is thought to be attributed, at least in part, to various myelin-associated inhibitors (MAIs), such as Nogo, myelinassociated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp) around the damaged site. Interestingly, these three structurally different inhibitors share two common receptors, Nogo-66 receptor (NgR) and paired immunoglobulin-like receptor B (PirB), and transduce the inhibitory signal into neurons via their complex combinant and co-receptors, such as p75 neurotrophin receptor (p75NTR), Nogo receptor-interacting protein 1 (LINGO-1), and TROY. Accordingly, targeting of the whole myelin or just portions by immunization has been proved to be neuroprotective and is able to promote regeneration in the injured spinal cords. In the past few years, vaccine approaches were initially achieved and could induce the production of antibodies against inhibitors in myelin to block the inhibitory effects and promote functional recovery in spinal cord injury (SCI) models by immunizing with MAIs, such as purified myelin, spinal cord homogenates, or their receptors with the concept of protective autoimmunity formulated. However, for safety consideration, further work is necessary before the immunotherapy strategies can be adopted to treat human injured spinal cords.

Update on the role of p75NTR in neurological disorders: A novel therapeutic target.

As a low-affinity neurotrophins receptor, p75 neurotrophin receptor (p75NTR) is a transmembrane receptor involved in a diverse array of cellular responses, including apoptosis, survival, neurite outgrowth, migration, and cell cycle arrest, which may be related to some neurological disorders, such as Alzheimer's disease (AD), schizophrenia, major depressive disorder (MDD), posttraumatic stress disorder (PTSD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Indeed, a series of studies during the last decade has demonstrated that the p75NTR signaling plays key roles in most aspects of the neurological disorder diseases. In spite of the limited information available, this review still tried to summary the relationship between p75NTR and diverse neurological disorder diseases, and tried to further clarify the possible mechanism, which may provide a novel therapeutic target for the treatment of neurological disorders.

Immunotherapy strategies for spinal cord injury.

Regeneration in the central nervous system (CNS) of adult mammalian after traumatic injury is limited, which often causes permanent functional motor and sensory loss. After spinal cord injury (SCI), the lack of regeneration is mainly attributed to the presence of a hostile microenvironment, glial scarring, and cavitation. Besides, inflammation has also been proved to play a crucial role in secondary degeneration following SCI. The more prominent treatment strategies in experimental models focus mainly on drugs and cell therapies, however, only a few strategies applied in clinical studies and therapies still have only limited effects on the repair of SCI. Recently, the interests in immunotherapy strategies for CNS are increasing in number and breadth. Immunotherapy strategies have made good progresses in treating many CNS degenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and multiple sclerosis (MS). However, the strategies begin to be considered to the treatment of SCI and other neurological disorders in recent years. Besides anti-inflamatory therapy, immunization with protein vaccines and DNA vaccines has emerged as a novel therapy strategy because of the simplicity of preparation and application. An inflammatory response followed by spinal cord injury, and is controled by specific signaling molecules, such as some cytokines playing a crucial role. As a result, appropriate immunoregulation, the expression of pro-inflammatory cytokines and anti-inflammatory cytokines may be an effective therapy strategy for earlier injury of spinal cord. In addition, myelinassociated inhibitors (MAIs) in the injured spinal cord, such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte- myelin glycoprotein (OMgp) are known to prevent axonal regeneration through their co-receptors, and to trigger demyelinating autoimmunity through T cell-mediated harmful autoimmune response. The antagonism of the MAIs through vaccinating with protein or DNA vaccines targeting Nogo, MAG, OMgp, and their co-receptors, may be an effective strategy for the treatment of SCI. However, immunotherapy such as anti-inflammtory therapy or vaccine targeting MAIs or their receptors, accompanied with the potential in risking autoimmune diseases. As a result, in order to optimize the anti-inflammtory therapy and design of protein or DNA vaccines for their use in the future clinical application, we need to further understand the possible mechanisms of neuroprotective immunity. This review presents recent advances in the development of immunotherapy strategies for the treatment of axonal degeneration and demyelination, and improvement of motor function after SCI.

Ameliorative Effects of p75NTR-ED-Fc on Axonal Regeneration and Functional Recovery in Spinal Cord-Injured Rats.

As a co-receptor of Nogo-66 receptor (NgR) and a critical receptor for paired immunoglobulin-like receptor (PirB), p75 neurotrophin receptor (p75NTR) mediates the inhibitory effects of myelin-associated inhibitors on axonal regeneration after spinal cord injury. Therefore, the p75NTR antagonist, such as recombinant p75NTR protein or its homogenates may block the inhibitory effects of myelin and promote the axonal regeneration and functional recovery. The purposes of this study are to subclone and express the extracellular domain gene of human p75NTR with IgG-Fc (hp75NTR-ED-Fc) in prokaryotic expression system and investigate the effects of the recombinant protein on axonal regeneration and functional recovery in spinal cord-injured rats. The hp75NTR-ED-Fc coding sequence was amplified from pcDNA-hp75NTR-ED-Fc by polymerase chain reaction (PCR) and subcloned into vector pET32a (+), then the effects of the purified recombinant protein on neurite outgrowth of dorsal root ganglion (DRG) neurons cultured with myelin-associated glycoprotein (MAG) were determined, and the effects of the fusion protein on axonal regeneration, functional recovery, and its possible mechanisms in spinal cord-injured rats were further investigated. The results indicated that the purified infusion protein could promote neurite outgrowth of DRG neurons, promote axonal regeneration and functional recovery, and decrease RhoA activation in spinal cord-injured rats. Taken together, the findings revealed that p75NTR still may be a potential and novel target for therapeutic intervention for spinal cord injury and that the hp75NTR-ED-Fc fusion protein treatment enhances functional recovery by limiting tissue loss and stimulating axonal growth in spinal cord-injured rats, which may result from decreasing the activation of RhoA.