Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in a rat hemisected spinal cord injury model

Nerve conduit is one of strategies for spine cord injury(SCI)treatment.Recently,studies showed that biomaterials could guide the neurite growth and promote axon regeneration at the injury site.However,the scaffold by itself was difficult to meet the need of SCI functional recovery.The basic fibroblast growth factor(bFGF)administration significantly promotes functional recovery after organ injuries.Here,using a rat model of T9 hemisected SCI,we aimed at assessing the repair capacity of implantation of collagen scaffold(CS)modified by collagen binding bFGF(CBD-bFGF).The results showed that CS combined with CBD-bFGF treatment improved survival rates after the lateral hemisection SCI.The CS/CBD-bFGF group showed more significant improvements in motor than the simply CS-implanted and untreated control group,when evaluated by the 21-point Basso-Beattie-Bresnahan(BBB)score and footprint analysis.Both hematoxylin and eosin(H&E)and immunohistochemical staining of neurofilament(NF)and glial fibrillary acidic protein(GFAP)demonstrated that fibers were guided to grow through the implants.These findings indicated that administration of CS modified with CBD-bFGF could promote spinal cord regeneration and functional recovery.     

bFGF通过抑制Nogo-A信号减少脊髓损伤后胶质瘢痕形成

脊髓损伤后胶质瘢痕的形成是阻碍神经恢复的关键原因之一。碱性成纤维细胞生长因子（basic fibroblast growth factor,bFGF）具有良好的神经保护及促进脊髓损伤的修复作用,然而其对于胶质瘢痕的影响及其机制仍不清楚。本研究通过采用血管动脉夹（30 g）夹闭雌性SD大鼠脊髓2 min造成急性脊髓损伤模型并予以每天皮下注射bFGF（80 μg/kg）,探讨bFGF促进脊髓损伤的恢复作用是否涉及到胶质瘢痕调控和Nogo-A/NgR信号的相关机制。通过检测损伤后28 d,各组BBB评分和斜板试验,发现bFGF显著促进脊髓损伤后大鼠运动功能的恢复。HE及尼氏染色显示,bFGF处理组相对于生理盐水处理组,其神经元明显增多,空洞面积减少。同时,星形胶质细胞标记物GFAP免疫荧光结果表明,bFGF减少胶质瘢痕形成,抑制星形胶质细胞过度激活。同样,通过Western 印迹检测发现,bFGF处理后,胶质瘢痕相关蛋白（如GFAP, neurocan）以及神经突生长抑制蛋白（Nogo-A）信号通路相关蛋白质表达量下降。上述结果表明,bFGF可能通过抑制Nogo-A信号蛋白的表达,从而抑制胶质瘢痕的形成,促进脊髓损伤的恢复。此机制研究为脊髓损伤的治疗和恢复提供全新的思路和药物靶点。     

Nanoparticle mediated controlled delivery of dual growth factors

Peripheral nerve functional recovery after nerve injury generally requires multiple growth factors by synergistic effect.However,the optical combination of multiple synergistic growth factors for axonal regeneration has been scarcely considered up to now.Meanwhile,the use of growth factors in promoting nerve regeneration was limited by its short biological half-life in vivo,its vulnerability to structure disruption or hydrolyzation,leading to loss of bioactivity.Herein,a novel polymeric nanoparticle delivery system composed of heparin andε-poly-L-lysine(PL)was prepared for control release of nerve growth factor(NGF)and basic fibroblast growth factor(bFGF).The nanoparticles were synthesized by polyelectrolyte complexation in aqueous solution at room temperature,followed by cross-linking with biological genipin.The obtained nanoparticles had a spherical shape,with a mean diameter of about 246 nm,and high growth factors encapsulation efficiency as well as good stability.NGF and bFGF were encapsulated in the nanoparticles and showed a continuous and slow release behavior in vitro.The bioactivities of the released growth factors were evaluated,and exhibited the synergistic effect.The controlled release of the dual synergistic growth factors would improve the treatment of peripheral nerve injury to mimic the natural cellular microenvironments.     

FGF1 improves functional recovery through inducing PRDX1 to regulate autophagy and anti‐ROS after spinal cord injury

Fibroblast growth factor 1 (FGF1) is thought to exert protective and regenerative effects on neurons following spinal cord injury (SCI), although the mechanism of these effects is not well understood. The use of FGF1 as a therapeutic agent is limited by its lack of physicochemical stability and its limited capacity to cross the blood‐spinal cord barrier. Here, we demonstrated that overexpression of FGF1 in spinal cord following SCI significantly reduced tissue loss, protected neurons in the ventricornu, ameliorated pathological morphology of the lesion, dramatically improved tissue recovery via neuroprotection, and promoted axonal regeneration and remyelination both in vivo and in vivo. In addition, the autophagy and the expression levels of PRDX1 (an antioxidant protein) were induced by AAV‐FGF1 in PC12 cells after H₂O₂ treatment. Furthermore, the autophagy levels were not changed in PRDX1‐suppressing cells that were treated by AAV‐FGF1. Taken together, these results suggest that FGF1 improves functional recovery mainly through inducing PRDX1 expression to increase autophagy and anti‐ROS activity after SCI.     

Chondroitinase and growth factors enhance activation and oligodendrocyte differentiation of endogenous neural precursor cells after spinal cord injury

The adult spinal cord harbours a population of multipotent neural precursor cells (NPCs) with the ability to replace oligodendrocytes. However, despite this capacity, proliferation and endogenous remyelination is severely limited after spinal cord injury (SCI). In the post-traumatic microenvironment following SCI, endogenous spinal NPCs mainly differentiate into astrocytes which could contribute to astrogliosis that exacerbate the outcomes of SCI. These findings emphasize a key role for the post-SCI niche in modulating the behaviour of spinal NPCs after SCI. We recently reported that chondroitin sulphate proteoglycans (CSPGs) in the glial scar restrict the outcomes of NPC transplantation in SCI by reducing the survival, migration and integration of engrafted NPCs within the injured spinal cord. These inhibitory effects were attenuated by administration of chondroitinase (ChABC) prior to NPC transplantation. Here, in a rat model of compressive SCI, we show that perturbing CSPGs by ChABC in combination with sustained infusion of growth factors (EGF, bFGF and PDGF-AA) optimize the activation and oligodendroglial differentiation of spinal NPCs after injury. Four days following SCI, we intrathecally delivered ChABC and/or GFs for seven days. We performed BrdU incorporation to label proliferating cells during the treatment period after SCI. This strategy increased the proliferation of spinal NPCs, reduced the generation of new astrocytes and promoted their differentiation along an oligodendroglial lineage, a prerequisite for remyelination. Furthermore, ChABC and GF treatments enhanced the response of non-neural cells by increasing the generation of new vascular endothelial cells and decreasing the number of proliferating macrophages/microglia after SCI. In conclusions, our data strongly suggest that optimization of the behaviour of endogenous spinal NPCs after SCI is critical not only to promote endogenous oligodendrocyte replacement, but also to reverse the otherwise detrimental effects of their activation into astrocytes which could negatively influence the repair process after SCI.     

Recombinant DNA Vaccine Against Inhibition of Neurite Outgrowth Promotes Functional Recovery Associated with Endogeous NGF Expression in Spinal Cord Hemisected Adult Rats

Axonal regeneration across the site of spinal cord lesion is often aborted in adult mammalian species. The use of DNA vaccine to nullify the inhibitory molecules has been shown to be effective in promoting axonal regeneration in injured spinal cord. The possible molecular mechanisms, however, remain to be elucidated. The present study showed that the administration of recombinant DNA vaccine encoding multiple domains, Nogo-66, Nogo-N, TnR, and MAG, significantly improved hindlimb locomotor functions in rats subjected to ablation of the dorsal halves of the cord. Western blot analysis demonstrated that nerve growth factor (NGF) levels in the spinal cord of immunized rats were significantly upregulated than those of control rats. Immunohistochemistry as well as in situ hybridization confirmed that NGF was expressed in neurons of the spinal cord. These findings indicated that functional recovery in immunized rats could be correlated with endogeous NGF expression in hemisected rat spinal cords. Y. Zhang and C.-G. Hao contributed equally to this work.     

Fibrin matrices with affinity‐based delivery systems and neurotrophic factors promote functional nerve regeneration

Glial‐derived neurotrophic factor (GDNF) and nerve growth factor (NGF) have both been shown to enhance peripheral nerve regeneration following injury and target different neuronal populations. The delivery of either growth factor at the site of injury may, therefore, result in quantitative differences in motor nerve regeneration and functional recovery. In this study we evaluated the effect of affinity‐based delivery of GDNF or NGF from fibrin‐filled nerve guidance conduits (NGCs) on motor nerve regeneration and functional recovery in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated consisting of GDNF or NGF and the affinity‐based delivery system (DS) within NGCs, control groups excluding the DS and/or growth factor, and nerve isografts. Groups with growth factor in the conduit demonstrated equivalent or superior performance in behavioral tests and relative muscle mass measurements compared to isografts at 12 weeks. Additionally, groups with GDNF demonstrated greater specific twitch and tetanic force production in extensor digitorum longus (EDL) muscle than the isograft control, while groups with NGF produced demonstrated similar force production compared to the isograft control. Assessment of motor axon regeneration by retrograde labeling further revealed that the number of ventral horn neurons regenerating across NGCs containing GDNF and NGF DS was similar to the isograft group and these counts were greater than the groups without growth factor. Overall, the GDNF DS group demonstrated superior functional recovery and equivalent motor nerve regeneration compared to the isograft control, suggesting it has potential as a treatment for motor nerve injury. Biotechnol. Bioeng. 2010;106: 970–979. © 2010 Wiley Periodicals, Inc.     

Epidermal growth factor attenuates blood‐spinal cord barrier disruption via PI3K/Akt/Rac1 pathway after acute spinal cord injury

After spinal cord injury (SCI), disruption of blood–spinal cord barrier (BSCB) elicits blood cell infiltration such as neutrophils and macrophages, contributing to permanent neurological disability. Previous studies show that epidermal growth factor (EGF) produces potent neuroprotective effects in SCI models. However, little is known that whether EGF contributes to the integrity of BSCB. The present study is performed to explore the mechanism of BSCB permeability changes which are induced by EGF treatment after SCI in rats. In this study, we demonstrate that EGF administration inhibits the disruption of BSCB permeability and improves the locomotor activity in SCI model rats. Inhibition of the PI3K/Akt pathways by a specific inhibitor, LY294002, suppresses EGF‐induced Rac1 activation as well as tight junction (TJ) and adherens junction (AJ) expression. Furthermore, the protective effect of EGF on BSCB is related to the activation of Rac1 both in vivo and in vitro. Blockade of Rac1 activation with Rac1 siRNA downregulates EGF‐induced TJ and AJ proteins expression in endothelial cells. Taken together, our results indicate that EGF treatment preserves BSCB integrity and improves functional recovery after SCI via PI3K‐Akt‐Rac1 signalling pathway.     

Transplantation of adult spinal cord grafts into spinal cord transected rats improves their locomotor function

Grafted embryonic central neural tissue pieces can recover function of hemisected spinal cord in neonatal rats and promote axonal growth in adults. However, spinal cord segments from adults have not been used as donor segments for allogeneic transplantation. Here, we utilized adult spinal cord tissue grafts(aSCGs) as donor constructs for repairing complete spinal cord injury(SCI). Moreover, to provide a favourable microenvironment for SCI treatment, a growth factor cocktail containing three growth factors(brain-derived neurotrophic factor, neurotrophin-3 and vascular endothelial growth factor), was applied to the aSCG transplants. We found that the locomotor function was significantly improved 12 weeks after transplantation of aSCGs into the spinal cord lesion site in adult rats. Transplantation of aSCGs combined with these growth factors enhanced neuron and oligodendrocyte survival and functional restoration. These encouraging results indicate that treatment of complete SCI by transplanting aSCGs, especially in the presence of growth factors, has a positive effect on motor functional recovery, and therefore could be considered as a possible therapeutic strategy for SCI.     

京尼平苷酸通过稳定微管促进脊髓损伤后轴突生长

脊髓损伤（spinal cord injury, SCI）是中枢神经系统最严重的创伤之一,其可造成患者感觉和运动功能障碍,并且引发一系列严重的并发症。促进轴突再生是修复脊髓损伤后功能恢复的关键因素。京尼平苷酸（geniposidic acid, GA）具有神经保护作用,但其在脊髓损伤后轴突生长的作用及机制方面尚未见报道。本研究通过提取原代神经元,并建立糖氧剥夺模型(oxygen glucose deprivation, OGD)。通过RT-PCR、Western印迹、免疫荧光等方法,探讨GA对神经元轴突的促进作用及其机制。结果发现,GA可以显著促进神经元轴突生长,并呈剂量依赖性。与OGD组神经元轴突长度（22±5.788 μm）相比,给予10 μmol/L的GA可使神经元轴突长度显著增加（68±17.73 μm）。同时,轴突生长相关蛋白（GAP43,MAP2）的基因和蛋白质水平都显著上升。不仅如此,我们发现,GA促进轴突生长与稳定神经元轴突微管相关,可使A/T的比值增加约1.5倍。同时,通过建立大鼠急性脊髓损伤模型评价GA在体内的效果,与对照组相比,每天腹腔注射GA（10 mg/kg）的大鼠在术后28 d的BBB评分（11.8分）和斜板试验（41.7°）均显著增高。上述结果表明,GA可能通过稳定微管从而促进轴突再生,最终促进脊髓损伤后运动功能的恢复。因此,GA 可能成为治疗脊髓损伤的有前景的候选药物。     

Neurotrophic factor gene delivery supports axonal regeneration after injury

A successful treatment for spinal cord injury (SCI) must include means to induce axonal regeneration and synaptogenesis. Though much research has demonstrated the effectiveness of neurotrophic factors (NFs) in supporting axonal regeneration, systemic delivery of doses sufficient to reach therapeutic concentrations and overcome their short half‐lives has caused adverse effects. Local expression of NFs would overcome these limitations. We tested whether local expression of NFs would induce axonal regeneration without adverse effects in two models of neural injury. In a chemical injury model the rat serotonergic system was lesioned with p‐chloroamphetamine. When an adenoviral vector carrying the gene for brain‐derived neurotrophic factor (BDNF) was injected into the denervated cortex BDNF expressed by the transfected cells induced serotonergic axon reinnervation only in area around the injection site. In a mechanical injury model the cortical spinal tract (CST) in rats was lesioned unilaterally at the level of the hindbrain. Neurotorphin‐3 (NT‐3) was expressed locally in the spinal cord either by direct injection of an adenoviral vector carrying the gene for NT‐3 or by retrograde delivery of the vector from the sciatic nerve. Axons were observed growing from the unlesioned CST across the midline to the denervated side. These data demonstrate that local expression of NFs will induce and support axonal regeneration in a circumscribed area after injury without adverse effects and suggest that a therapy for SCI based upon this strategy may include NF gene delivery. Acknowledgements: Supported by NIH grant NS35280 and Mission Connect of the TIRR Foundation.     

Regulation of Autophagy and Ubiquitinated Protein Accumulation by bFGF Promotes Functional Recovery and Neural Protection in a Rat Model of Spinal Cord Injury

The role of autophagy in the recovery of spinal cord injury remains controversial; in particular, the mechanism of autophagy regulated degradation of ubiquitinated proteins has not been discussed to date. In this study, we investigated the protective role of basic fibroblast growth factor (bFGF) both in vivo and in vitro and demonstrated that excessive autophagy and ubiquitinated protein accumulation is involved in the rat model of trauma. bFGF administration improved recovery and increased the survival of neurons in spinal cord lesions in the rat model. The protective effect of bFGF is related to the inhibition of autophagic protein LC3II levels; bFGF treatment also enhances clearance of ubiquitinated proteins by p62, which also increases the survival of neuronal PC-12 cells. The activation of the downstream signals of the PI3K/Akt/mTOR pathway by bFGF treatment was detected both in vivo and in vitro. Combination therapy including the autophagy activator rapamycin partially abolished the protective effect of bFGF. The present study illustrates that the role of bFGF in SCI recovery is related to the inhibition of excessive autophagy and enhancement of ubiquitinated protein clearance via the activation of PI3K/Akt/mTOR signaling. Overall, our study suggests a new trend for bFGF drug development for central nervous system injuries and sheds light on protein signaling involved in bFGF action.     

miR-22-3p enhances the intrinsic regenerative abilities of primary sensory neurons via the CBL/p-EGFR/p-STAT3/GAP43/p-GAP43 axis

Spinal cord injury (SCI) is a devastating disease. Strategies that enhance the intrinsic regenerative ability are very important for the recovery of SCI to radically prevent the occurrence of sensory disorders. Epidermal growth factor (EGF) showed a limited effect on the growth of primary sensory neuron neurites due to the degradation of phosphorylated-epidermal growth factor receptor (p-EGFR) in a manner dependent on Casitas B-lineage lymphoma (CBL) (an E3 ubiquitin-protein ligase). MiR-22-3p predicted from four databases could target CBL to inhibit the expression of CBL, increase p-EGFR levels and neurites length via STAT3/GAP43 pathway rather than Erk1/2 axis. EGF, EGFR, and miR-22-3p were downregulated sharply after injury. In vivo miR-22-3p Agomir application could regulate CBL/p-EGFR/p-STAT3/GAP43/p-GAP43 axis, and restore spinal cord sensory conductive function. This study clarified the mechanism of the limited promotion effect of EGF on adult primary sensory neuron neurite and targeting miR-22-3p could be a novel strategy to treat sensory dysfunction after SCI.     

Effects of combining methylprednisolone with rolipram on functional recovery in adult rats following spinal cord injury

Methylprednisolone (MP) has been widely used as a standard therapeutic agent for the treatment of spinal cord injury (SCI). Because of its controversial beneficial effects, the combination of MP and other pharmacological agents aimed at enhancing functional recovery is desirable. The phosphodiesterase 4 (PDE4) inhibitor rolipram has been implicated in promotion of regeneration due to elevating cAMP. In the present study, we sought to determine the effects of MP and rolipram, administered in combination, after spinal cord injury (SCI) in adult rats. Here we show that in vitro administration of rolipram and MP significantly increased neuron survival and promoted neurite outgrowth of neurons on the inhibitory substrate CSPGs by upregulation of MMP-2 expression; in vivo administration of rolipram and MP inhibited CSPG expression and increase CSPG digestion after rat SCI. Rolipram and MP combining treatment promoted significant neuroprotection through reduced motoneuron death, minimized lesion cavity, and increased regeneration of lesioned corticospinal tract (CST) axons beyond the lesion site after SCI. Enhanced functional recovery was also observed. Overall, our study strongly suggested that the combination treatment of MP and rolipram may represent a promising strategy for clinically applicable pharmacological therapy for rapid initiation of neuroprotection after SCI.     

Biochemical Monitoring of Spinal Cord Injury by FT-IR Spectroscopy—Effects of Therapeutic Alginate Implant in Rat Models

Spinal cord injury (SCI) induces complex biochemical changes, which result in inhibition of nervous tissue regeneration abilities. In this study, Fourier-transform infrared (FT-IR) spectroscopy was applied to assess the outcomes of implants made of a novel type of non-functionalized soft calcium alginate hydrogel in a rat model of spinal cord hemisection (n = 28). Using FT-IR spectroscopic imaging, we evaluated the stability of the implants and the effects on morphology and biochemistry of the injured tissue one and six months after injury. A semi-quantitative evaluation of the distribution of lipids and collagen showed that alginate significantly reduced injury-induced demyelination of the contralateral white matter and fibrotic scarring in the chronic state after SCI. The spectral information enabled to detect and localize the alginate hydrogel at the lesion site and proved its long-term persistence in vivo. These findings demonstrate a positive impact of alginate hydrogel on recovery after SCI and prove FT-IR spectroscopic imaging as alternative method to evaluate and optimize future SCI repair strategies.     

Multiple growth factor delivery for skin tissue engineering applications

Administration of exogenous growth factors (GFs) to a damaged site has been investigated for skin tissue regeneration. Among the many types of GFs and cytokines, epidermal growth factor, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, and hepatocyte growth factor could be specifically used for stimulating molecules in wound healing as well as for recovery of damaged skin tissues. It is speculated that delivered GFs could stimulate various cellular functions, including proliferation, migration, deposition of extracellular matrix molecules, and remodeling of collagen synthesis. Although the physiological wound healing process is complex, engineering strategies for proper delivery of multiple therapeutic GFs could enhance the quality and quantity of regenerated skin tissues. As compared to single delivery of a GF, recent studies have proven that any combination of multiple GFs and/or therapeutic chemical factors synergistically facilitates the regeneration of damaged skin tissues. In order to maximize the stability, bioactivity, intrinsic therapeutic functionality, and efficiency of internal delivery of cargo GFs, it is essential to utilize tissueengineered biomaterials and related composites as implantable platforms. Successful fabrication and development of skin tissue engineering applications as well as subsequent surgical implantation of these platforms might provide clinical treatment for superior skin regeneration. Therefore, the present review summarizes the biological functions, related signaling mechanisms, and recent developments of tissue engineering applications for multiple GF delivery.     

肌肉注射人神经生长因子基因逆轴突传递修复神经损伤的研究进展

神经生长因子(NGF)促进中枢及外周神经系统神经元细胞存活、分化、轴突再生等重要作用已得到临床的广泛证实。目前临床上主要以局部或肌肉注射NGF蛋白的方式对神经系统的损伤进行治疗。但NGF半衰期短、局部应用副作用大、费用昂贵、难以透过血脑屏障等缺点而限制临床应用。长期以来,科研工作者致力于寻求一种理想的途径或方法以克服这一缺陷。随着基因工程技术的飞速发展,研究人员发现通过骨骼肌肌肉注射途径,以非病毒载体介导外源的NGF基因体内表达并逆轴突传递到神经损伤部位,有望解决这一难题。本文将就NGF及受体的基本结构和特性、逆轴突传递的机制、非病毒载体结合骨骼肌肌肉注射的基因治疗等方面进行总结和阐述。     

Growth factor receptors in amyotrophic lateral sclerosis

The regional distribution of nerve growth factor (NGF) and insulin-like growth factor-1 (IGF-1) receptors in human spinal cords from controls and amyotrophic lateral sclerosis (ALS) patients was studied by quantitative autoradiography. High-affinity nerve growth factor receptors were found to be distributed to a similar extent within the various segments of the human spinal cord and predominantly within the substantia gelatinosa of the dorsal horn, whereas no significant binding could be detected in the motor-neuron areas. A similar pattern of binding was obtained in the ALS spinal cords. Moreover, no reexpression of NGF receptors could be demonstrated in the motor-neuron areas of ALS spinal cords. When comparing¹²⁵I-IGF-1 binding in the different spinal levels of normal spinal cord, the same distribution pattern was found in which the binding was highest in the central canal > dorsal horn > ventral horn > white matter. In the ALS cases, although a general upregulation of IGF-1 receptors was observed throughout the spinal cord, significant increases were observed in the cervical and sacral segments compared to controls. The cartography of IGF-1 receptors in the normal spinal cord as well as the change of these receptors in diseased spinal cord may be of importance in future treatment strategies of ALS.     

The human natural killer-1 (HNK-1) glycan mimetic ursolic acid promotes functional recovery after spinal cord injury in mouse

Human natural killer-1 (HNK-1) cell antigen is a glycan epitope involved in several neural events, such as neuritogenesis, myelination, synaptic plasticity and regeneration of the nervous system after injury. We have recently identified the small organic compound ursolic acid (UA) as a HNK-1 mimetic with the aim to test its therapeutic potential in the central nervous system. UA, a plant-derived pentacyclic triterpenoid, is well known for its multiple biological functions, including neuroprotective, antioxidant and anti-inflammatory activities. In the present study, we evaluated its functions in a mouse model of spinal cord injury (SCI) and explored the molecular mechanisms underlying its positive effects. Oral administration of UA to mice 1 h after SCI and thereafter once daily for 6 weeks enhanced the regaining of motor functions and axonal regrowth, and decreased astrogliosis. UA administration decreased levels of proinflammatory markers, including interleukin-6 and tumor necrosis factor-α, in the injured spinal cord at the acute phase of inflammation and activated the mitogen-activated protein kinase and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways in the injured spinal cord. Taken together, these results suggest that UA may be a candidate for treatment of nervous system injuries.     

药物及靶向治疗在脊髓损伤中的治疗新进展

脊髓损伤(spinalcordinjury,SCI)是一种严重的损伤,它对患者的影响是相当持久的,SCI治疗的难点主要是由于损伤后脊髓中的微环境不利于神经细胞的再生、轴突的生长和新突触的形成,从而影响了脊髓组织的修复。现在SCI治疗的策略就是要改善损伤脊髓微环境,减少不利因素,从而促进脊髓结构修复和功能重建。本研究综述近年来逐渐发展起来的药物及靶向治疗方法,为SCI的新治疗提供参考依据,真正提高患者的生活质量。