【作者】 卢培刚；

【导师】 冯华；

【作者基本信息】 第三军医大学 ， 外科学， 2008， 博士

【摘要】 神经保护是指在神经损伤发生前或神经损伤早期采用药物治疗或某些处理措施将神经的损伤降低到最低程度的一种治疗策略。脊髓损伤防治涵盖的内容较广,涉及继发损害的防治、亚急性/慢性阶段的神经保护、轴索/神经元的持续再生以及神经再支配的获得。每一部分又包含着若干亟待解决的课题。近20年来国内外学者对脊髓损伤的生物学机制进行了大量的实验和临床研究,已经在细胞水平和分子水平对脊髓损伤机制有了更深入的了解,在此基础上研究者致力于寻求神经保护治疗手段,以求改善脊髓损伤的预后。预处理作为一种与传统有别的神经保护的重要防治手段,近年来已开始越来越多地引起人们的兴趣和关注,成为神经科学研究领域中的一个热点。预处理可触发或动员机体内在的防御系统,从而对随后的严重损伤产生强大的保护作用。目前对于低氧缺血预处理对中枢神经缺血再灌注损伤保护的研究取得了很大的进展,还有药物预处理的研究也不断深入,因上述预处理受伦理学限制,难以在临床推广,故高压氧预处理有良好的应用前景。但高压氧预处理对脊髓损伤神经保护的研究尚处于初级探索阶段。本实验采用SD大鼠为脊髓损伤打击模型,分组给予高压氧和低压缺氧预处理,观察预处理对脊髓损伤的神经保护效应,并对保护机制进行初步探讨,同时对高压氧治疗脊髓损伤的疗效给予评估。本文共分为以下三个部分内容:一、高压氧和低压缺氧预处理对大鼠脊髓损伤后神经保护效应的实验研究目的:通过建立高压氧和低压缺氧预处理脊髓损伤动物模型,观察预处理对成年大鼠急性脊髓损伤后不同时期神经功能的影响,以探讨预处理对脊髓损伤后的神经保护效应。方法:1、高压氧和低压缺氧预处理动物模型的建立:成年雌性大鼠随机分组后,利用实验动物高压氧舱和低压氧舱,在相应的实验条件下,分别预处理5天。2、脊髓损伤模型的建立:麻醉状态下,手术显露椎管及硬膜囊,用30g冲击棒自5cm高度自由落体下坠致伤脊髓。冲击棒下端直径3mm,致伤能量为150gcf,建立脊髓损伤模型。3、观察项目:(1)行为学评价:采用BBB运动功能评分法,分别在脊髓损伤后1d、1w、2w、4w和8w进行评分。(2)诱发电位的测定:各组大鼠分别在损伤后不同时期测定体感诱发电位和运动诱发电位检测。(3)透射电镜:灌注固定后取损伤区中心1mm3置入10%戊二醛液,制片,电镜下观察采图。(4) HE染色光镜下观察:各组大鼠分别在损伤后不同时期灌注固定取材,行脊髓矢状和冠状石蜡切片的HE染色观察(6)神经束路示踪:生物素化萄聚糖胺顺行示踪和辣根过氧化物酶逆行示踪,观察上行和下行轴突再生情况,预处理对轴突再生的影响。4、实验内容数据采用SPSS12.0软件进行统计处理。结果:1、本实验高压氧和低压缺氧预处理及大鼠脊髓打击伤模型建立可靠稳定,具有较好的可重复性。2、大鼠脊髓打击模型在伤后1d BBB评分为0分,1w为2.86+1.03分,以后逐渐恢复,8w为14.12+2.15分,经高压氧和低压缺氧预处理后在各时期与非预处理损伤组相比较,1w为3.56+2.43分和3.98+0.02分,8w分别为15.63+2.02分和16.38+1.18分,评分明显增高,低压缺氧预处理组更为明显,差异有显著性(p<0.05),4w后进入平台期。3、运动诱发电位和体感诱发电位的潜伏期在脊髓损伤后明显延长, 1w MEP及SEP潜伏期分别为(30.68+4.35)ms和(25.38+1.42)ms,4w后分别为(17.98+6.62)ms和(18.08+3.12)ms ,经高压氧和低压缺氧预处理1w分别为(27.56+5.86)ms、(24.15+1.23)ms和(24.21+3.69)ms、(24.15+1.23)ms,4w后分别为(14.67+2.05)ms、(17.05+5.02)ms和(17.42+2.75)ms、(15.26+3.16)ms,在1w-4w各时期与非预处理损伤组相比较,潜伏期缩短,低压缺氧预处理组更为明显,差异有显著性(p<0.05),4w后相对稳定。4、光镜及电镜观察:脊髓损伤后1d可见,损伤区中央灰质出现大片出血、细胞肿胀、尼氏体消失,并有大量单核或多核炎性细胞浸润;脊髓损伤第1w损伤区组织出现大片坏死灶,炎性反应加剧;2w后脊髓损伤及周围区炎性细胞浸润减轻,4w损伤脊髓组织出现囊腔样变化,8w以胶质瘢痕为主。电镜下凋亡样细胞主要表现为胞浆减少,核深染、固缩状态。经高压氧和低压缺氧预处理后脊髓损伤2w内,病理变化较非预处理损伤组减轻,尤其在损伤区周围更为明显,4w后差异不显著。5、神经束路示踪显示经高压氧和低压缺氧预处理后,上行和下行示踪标志阳性纤维明显增多,低压缺氧预处理组较高压氧预处理组更为显著。结论:1、大鼠打击伤SCI模型与人类SCI有一定相似性,个体差异不明显,模型制备简单,稳定重复性强。2、高压氧和低压缺氧预处理后,大鼠在脊髓损伤后不同时期脊髓功能改善,运动诱发电位和体感诱发电位潜伏期缩短,病理变化减轻,神经束路示踪标志阳性纤维明显增多,提示对大鼠脊髓损伤均有神经保护作用。3、高压氧和低压缺氧预处理对大鼠脊髓损伤具有一定的神经保护作用。(本实验建立的是中度脊髓损伤模型)。4、在本实验条件下,低压缺氧预处理对脊髓损伤的内源性保护作用较高压氧预处理的保护作用更为显著。二、高压氧和低压缺氧预处理对大鼠脊髓损伤后神经保护作用机制的探讨目的:探讨高压氧和低压缺氧预处理对大鼠脊髓损伤后神经保护作用机制,为脊髓损伤的防治提供理论基础。方法:预处理及脊髓打击伤实验动物模型建立分组后,在不同时期内取材,行免疫组织化学染色,RT-PCR和Westblot(蛋白印迹法)检测,观察预处理对脊髓损伤后神经细胞凋亡、神经干细胞、神经胶质细胞、血管内皮生长因子、轴突生长抑制因子和嘌呤受体的影响。实验内容数据采用SPSS12.0软件进行统计处理。观察项目:1、神经细胞凋亡,TUNEL染色观察2、GFAP免疫组织化学染色观察3、Nestin免疫组织化学染色观察4、VEGF免疫组织化学染色观察5、Nogo免役组织化学染色观察6、P2X7嘌呤受体mRNA和蛋白的定量观察结果:1、非预处理脊髓损伤1d TUNEL阳性细胞逐渐增多,分布不均匀,灰质和白质中均可见,1w后TUNEL染色的阳性细胞逐渐减少,阳性细胞主要位于周围白质中, 2w后可见少量的阳性细胞。经预处理后细胞凋亡出现的时间与非预处理损伤组基本相似,但分布和数量不同,即损伤区内TUNEL阳性细胞数相对较少, TUNEL阳性细胞主要分布在损伤区的边缘部位,1w后TUNEL阳性细胞较非预处理损伤组明显减少。2、GFAP表达于正常脊髓的中央灰质和周围白质。非预处理损伤组:1d在损伤区周围增加,2w达到高峰,以脊髓中央管室管膜区表达最为明显。4w囊腔开始形成,GFAP主要表达在囊腔周围的星形胶质细胞的胞体及突起,数量减少。低压缺氧预处理组:2w内阳性细胞数量明显增多,4w明显减少,而高压氧预处理组在各时期表达与非预处理损伤组比较明显增加。3、非预处理SCI1w,脊髓实质中即可见到少量的nestin免疫染色阳性细胞,2 w后观察到大量的nestin免疫染色阳性细胞,胞体为多角形或卵圆形,有较多突起,部分细胞突起的伸展方向和细胞的长轴一致,损伤附近的脊髓灰质可见少数nestin呈阳性表达的神经元,4 w以后, nestin阳性表达明显下调。预处理后1w-4w表达增加,尤其以低压缺氧预处理组更为显著。4、非预处理SCI 1d VEGF在大鼠脊髓损伤区及损伤周边区高表达,主要出现在软脊膜和脊髓灰、白质血管壁上的血管内皮细胞胞浆内,脊髓灰、白质内的神经胶质细胞和巨噬细胞胞浆内也出现表达,一般脊髓白质中更为多见,1w后下调,而预处理组1w VEGF的表达较正常组增加。5、非预处理SCI后1d,在脊髓损伤区中央,未见到nogo阳性细胞。2w后,损伤区附近白质, nogo阳性免疫细胞有少量表达,SCI后8w,见胶质瘢痕区nogo阳性表达反应,并且nogo表达阳性区与胶质瘢痕区相一致;高压氧和低压缺氧预处理组与非预处理损伤组表达无差异。6、SCI后P2X7受体的表达变化:在低压缺氧预处理组,伤后12h、3d、5d目的条带几乎不可见,而高压氧预处理组和非预处理损伤组却表现明显,尤其高压氧预处理组在12h表达更为明显。伤后7d三组无明显差异。结论:1、高压氧和低压缺氧预处理均可以通过抑制神经细胞凋亡起到神经保护作用。2、在脊髓损伤的早期(本实验观察到为2w之内),高压氧和低压缺氧预处理均可以促进星形胶质细胞活化,起到保护神经元的作用。脊髓损伤后期(本实验观察到为4w之后),高压氧预处理有促进胶质细胞过度增生,增强胶质瘢痕形成的可能。3、脊髓损伤后可以激活神经干细胞或前体细胞,高压氧和低压缺氧预处理均可以促进神经干细胞增殖和分化,尤其低压缺氧预处理更为显著。4、脊髓损伤可以导致内源性VEGF在脊髓实质中的表达增强,高压氧和低压缺氧预处理可以促进这一过程,通过促进血管生成、改善局部微循环间接地保护神经免受缺血缺氧损伤。5、脊髓损伤后期(本实验观察到为4w之后),轴突生长抑制因子nogo的高表达是影响轴突生长的重要因素,高压氧和低压缺氧预处理对脊髓损伤后nogo表达的影响不显著。6、低压缺氧预处理可以在短期内通过抑制P2X7受体的表达,对脊髓损伤起到神经保护作用,而高压氧预处理则不能,是通过其他途径起到神经保护作用的。三、高压氧治疗实验性大鼠脊髓损伤的疗效评价目的:通过分组高压氧治疗,评估治疗效果,为脊髓损伤的治疗提供依据。方法:1、实验大鼠分为四组:非预处理损伤组、非预处理损伤后高压氧治疗组、高压氧预处理后的高压氧治疗组和低压缺氧预处理后的高压氧治疗组,立即分别给予高压氧治疗2周。2、观察项目:(1)行为学评价:采用BBB运动功能评分法,分别在治疗后1w、2w、4w和8w进行评分。(2)诱发电位的测定:各组大鼠分别在治疗后不同时期进行体感诱发电位和运动诱发电位检测。(3)透射电镜:灌注固定后取损伤区中心1mm3置入10%戊二醛液,制片,电镜下观察采图。(4) HE染色光镜下观察:各组大鼠分别在治疗后不同时期灌注固定取材,行脊髓石蜡切片的HE染色观察。(5)免疫组织化学染色:观察高压氧治疗后nestin和GFAP的表达变化。(6)神经束路示踪:生物素化萄聚糖胺(BDA)顺行示踪观察下行轴突再生情况,观察高压氧治疗对轴突再生的影响。3、实验内容数据采用SPSS12.0软件进行统计处理。结果:1、经高压氧治疗后各组在各时期与非预处理损伤组相比较,评分明显增高,非预处理损伤组SCI后1w为2.86+1.03分,8w为14.12+2.15分,而低压缺氧预处理后高压氧治疗组1w为5.38+1.22分,8w为18.18+1.72分,差异最为明显(p<0.01)。2、运动诱发电位和体感诱发电位的潜伏期在脊髓损伤后明显延长,经高压氧治疗后各组在各时期与非预处理损伤组相比较,潜伏期缩短,低压缺氧预处理后高压氧治疗组更为明显,差异有显著性。3、经高压氧治疗后各组在各时期与非预处理损伤组相比较病理变化减轻,尤其在损伤区周围更为明显。4、经高压氧治疗后各组GFAP和nestin表达增加,2 w-4 w较非预处理损伤组差异显著,低压缺氧预处理后高压氧治疗组更为明显。5、神经束路示踪显示高压氧治疗后损伤区远端及胶质瘢痕周围的下行阳性纤维增加。结论:1、SCI后早期行高压氧治疗可以减轻脊髓损伤后的病理反应,促进内源性神经干细胞增殖,促进胶质细胞活化,促进轴突再生,有利于脊髓损伤后神经功能恢复。2、脊髓损伤前行低压缺氧预处理,损伤后立即行高压氧治疗,是脊髓损伤防治的重要策略之一。更多还原

【Abstract】 Neuroprotection treatment is applied before or after nerve injury by means of medicine or some special procedure to minimize the degree of nerve injury.There are many aspects of prevention and cure for spinal cord injury(SCI),including prevention for secondary lesion,neuroprotection for subacute and chronic stage,neuraxis and neuron regeneration and reinnervation obtaining etc.,and there are many issues remained unclear in each aspect.In the past two decades, researchers in and abroad did a lot experimental and clinical studies to investigate the biology mechanism of SCI,which led to a more profound understanding of SCI on cellular and molecular level.Based on these researches,this study is to explore new neuroprotection treatment for improving the prognosis of SCI. Preconditioning is an important prevention method which is different from traditional neuroprotection treatments,and researchers has been paying more and more attention on this new subject.Preconditioning could mobilize the defence system in corpore so as to produce powful protection for the sequentia major injury.Hypoxia preconditioning has been studied a lot in the protection for ischemical reperfusion injury in central nervous system and made significant progress,but the study of its role in SCI protection is just started.This study utilized SD rat as a SCI model, divided them into different groups applying hyperbaric oxygen(HBO) and hypobaric hypoxia preconditioning respectively, observed the neuroprotective effect for SCI,investigated its possible mechanism in each group,and also evalutaed the curative effect of HBO treatment for SCI.There are three parts in this study as follows:1.neuroprotective effect of HBO and hypobaric hypoxia preconditioning on SCI in ratsObject:To establish an animal model for HBO and hypobaric hypoxia preconditioning, investi- gate the impact of such preconditioning on the adult rat in different preriod after acute SCI,and evaluate the neuroprotective effect of such preconditioning in SCI.Method:1) Animal model establishment for HBO and hypobaric hypoxia preconditioning:SD rats were divided into two groups randomly,and preconditioned for 5 days respectively in HBO or hypobaric hypoxia chambers.2) SCI animal model establishment: Micrurgy were applied on the rats under anaesthesia to expose canalis spinalis and dural sac,utilizing a 30g lash stick to strike on the spinal cord from a height of 5 cm.The inferior extremity of the lash stick is 3 mm in diameter,with a shock energy of 150 gcf.3) Observation items:(1) Behavioral assessment:We applied BBB motor function score system in this study, and assessed the score at 1d,1w,2w,4w,and 8w after SCI.(2) Evoked potential examination: Somatosensory evoked potentia(SEP) and motor evoked potential(MEP)were detected at different time after SCI in each group.(3) Transmission electron microscope(TEM) observation:We removed a volume of 1 mm3 tissue right in the central of the injured region after being reperfused and fixed,placed the tissue into 10% glutaric dialdehyde fluid,made TEM slices and did the observation.(4) HE dyeing and observation under light microscope: the samples of spinal cord were obtained at different time after SCI, made paraffin section in anteroposterior axes,performed HE dyeing and observed the slices under light microscope.(5) Nerve-tract tracing: Anterogradely and retrogradely traceing were performed using biotin dextran amine(BDA) and horseradish peroxidase(HRP) respectively,observed the regenerated neuraxis ascendingly and descendingly,so as to identify the effect of such preconditioning on neuraxis regeneration.4) Data were analyzed by using SPSS12.0 statistics software.Result:1)The experimental animal model established is reliable and stable,presenting a good repeatability.2) The BBB score was dramatically dropped right after SCI,and then gradually increased afterward.The score of preconditioning groups was higher than the control group,especially in the hypobaric hypoxia group of which the difference was significant;the score in all groups entered a platform 4w after the SCI.3) SEP and MEP showed a prolonged lantency after SCI in all groups,the lantency in preconditioning groups was shorter compared with control group, and there was significant difference in hypobaric hypoxia preconditioning group.The SEP and MEP was relatively stable 4w after SCI.4) light microscope and TEM observation: In control group, the central gray of injured region appeared hemorrhage,cellular swelling,tigroid body abolition,and a great quantity of mononuclear or polynuclear inflammatory cells infiltration at 1d after SCI;Necrosis focuses appeared in injured region at 1w after SCI,and the inflammatory reaction was stronger;the inflammatory cell infiltration began to abate at 2w after SCI in injured and peri-injured region;capsular space-like change occurred in injured myeloid tissue at 4w after SCI, and at 8w after SCI glial scar became the major component.Apoptotic cells showed cytoplasm depletion,karyo-anachromasis and karyopyknosis under electron microscope.In HBO and hypobaric hypoxia preconditioning groups,the pathological change were less severe within 2w after SCI compared with control group,especially the surrounding area of injured region,and no significant difference were found after 4w after SCI.5) Nerve tract tracing revealed that the number of regeneration neuraxis ascending and descending increased in preconditioning groups,of which the hypobaric hypoxia group was much more obvious.Conclusion:1)the rat SCI model is resemblant with human SCI ,which is reliable with an insignificant individual difference and a good reproducibility,and a simple preparation process.2) Compared with the control group,rats in the preconditioning groups present a higher BBB score,a shorter lantency of SEP and MEP,a less severe pathological change,an increased regeneration neuraxis etc.,which indicate a neuroprotective effect of such preconditioning on rat SCI.3) Our study indicates that HBO and hypobaric hypoxia preconditioning have an effect of neuroprotection at certain degree.4) Hypobaric hypoxia preconditioning is more effective in neuroprotection for SCI than HBO preconditioning.2.Mechanism of the neuroprotective effect of HBO and hypobaric hypoxia preconditioning in rat SCI.Object:To investigate the mechanism of the neuroprotective effect of HBO and hypobaric hypoxia preconditioning in rat SCI,so as to provide rationale for its clinical application.Method:After divided into different groups for distinct preconditioning situation and preparation for SCI model, samples were collected at different time after SCI,then immunohistochemistry,RT-PCR and Westernblot were performed to identify neurocyte apoptosis,nerve stem cells,neuroglia cells,vascular endothelial growth factor,axon growth inhibitor and purinoceptor etc. Data were analyzed by using SPSS12.0 statistics software.Observation items:1) neurocyte apoptosis observation by means of TUNEL.2) immunohistochemistry for GFAP observation.3) immunohistochemistry for Nestin observation.4) immunohistochemistry for VEGF observation.5) immunohistochemistry for Nogo observation.6) quantitative observation for P2X7 purinoceptor.Result:1)In control group,apoptotic-positive cells increased from 1d after SCI,with a maldistribution in both gray and white matter, then gradually deceased from 1w after SCI with a mainly distribution in white matter surrounding the injured area,and only few apoptic-positive cells were found 2w after SCI.In preconditioning groups apoptic-positive cells appeared simultaneously with control group,but mainly concentrated in marginal part of injured region,and at 1w after SCI the apoptic-positive cells in preconditioning groups are much more less than that in control group.2) GFAP expresses in both gray matter and white matter in normal spinal cord.In the control group,GFAP expression began to increase surrounding the injured region at 1d till 2w after SCI,especially in the ependyma of spinal medullary canal.Capsular space began to form 4w after SCI,and GFAP expression decreased and mainly centered in the glia cell body and process surrouding the capsular space.GFAP expression in HBO preconditioning group is similar with control group;while in the hypobaric hypoxia preconditioning group,GFAP-positive cells were notablely increased at 2w after SCI and significantly decreased at 4w after SCI compared with control group.3) In control group,a few nestin immunostaining positive cells were observed at 1w after SCI in spinal cord parenchyma,and at 2w after SCI,a large amount of nestin-positive cells were seen.Most nestin-positive cells were polygon or orbicular-ovate in cell body with a lot of processes, which extended coincidently with the cell long axis;a minority of nestin-positive neurons were found in the vicinal gray matter of injured region.Nestin- positive cells were obviously decreased at 4w after SCI.In the preconditioning groups, nestin expression was stronger than that in control group after SCI,and hypobaric hypoxia preconditioning group is much more significant.4) VEGF expression increased in the injured and perimeter region at 1d after SCI,mainly in the cytoplasm of vascular endothelia cell(VEC) of the spinal pia mater and gray and white matter of spinal cord, as well as glial cell and macrophage of white matter;VEGF expression began to decrease at 1w after SCI.While in the preconditioning groups, VEGF expression was stronger than that of control group.5) In control group, no nogo-positive cells were found at 1d after SCI;2w later,a few nogo-positive cells were observed in the white matter nearby the injured region;8w after SCI,nogo were strongly expressed in the glial scar.No significant difference were seen in preconditioning groups.6) P2X7 receptor expression:In the HBO preconditioning and control group,strap for P2X7 receptor were obtained at 12h,3d and 5d after SCI,while in the hypobaric hypoxia preconditioning group nothing were found.No significant difference were found after between each group 7d after SCI.Conclusion:1)HBO and hypobaric hypoxia preconditioning has an effect of inhibiting nerve cell apoptosis;2) In the early state after SCI,HBO and hypobaric hypoxia preconditioning could both promote horizontal cell activation so as to protect neuron;while in the later stage, it may facilitate the hyperplasy of glial cell to form glial scar.3) Spinal cord injury could activate nerve stem or precursor cell,and HBO and hypobaric hypoxia preconditioning have an effect of promoting nerve stem or precursor cell proliferation and differentiation,while hypobaric hypoxia preconditioning is more effective.4) VEGF expression is stronger after SCI, and both preconditioning treatments could enhance its expression,thus to promote vascularizaiton and improve microcirculation to protect the nerve from hypoxia.5) In the later stage after SCI,the strong expression of axon growth inhibitor nogo may play an important role in hindering axon growth,and both HBO and hypobaric hypoxia preconditioning has no obvious impact on the nogo expression.6) After SCI,hypobaric hypoxia preconditioning could inhibit P2X7 receptor expression in a short term so as to lead a neuroprotective role,however,the HBO preconditioning is not involved in the same process.3.Evaluation of curative effect of HBO on experimental rat SCI Object:To evaluate the curative effect of HBO on rat SCI and provide reliable evidence for its clinical useage.Method:1)Rats were divided into 4 groups:SCI control group(group 1),SCI with HBO therapy group(group 2),SCI with HBO preconditioning and HBO therapy group(group 3) and SCI with hypobaric hypoxia preconditioning and HBO therapy group(group 4).The HBO therapy duration is 2w.2) Observation items:(1) behavioral assessment: BBB motor function score system was utilized in this study, and assessed the score at 1d,1w,2w,4w,and 8w after SCI.(2) Evoked potential examination: Somatosensory evoked potentia(SEP) and motor evoked potential(MEP)were detected at different time after SCI in each group.(3) TEM observation:Removed a volume of 1 mm3 tissue right in the central of the injured region after being perfused and fixed,placed the tissue into 10% glutaric dialdehyde fluid,made TEM slices and did the observation.(4) HE dyeing and observation: the samples of spinal cord were obtained at different time after SCI, made paraffin section in anteroposterior axes,performed HE dyeing and observed the slices under light microscope.(5) immunohistochemistry for nestin and GFAP expression.(6) Nerve-tract tracing: Anterogradely traceing were performed using biotin dextran amine(BDA) to see the regeneration of neuraxis descendingly,so as to identify the effect of HBO therapy on SCI.3) Data were analyzed by using SPSS12.0 statistics software.Result:1)BBB score in HBO therapy groups are higher than the control group,and the difference between group4 and group 1 is significant.(2) SEP and MEP showed a prolonged lantency after SCI in all groups,while after HBO therapy,the lantency in group2,3 and 4 is shortened compared with group1,and the difference in group 4 is significant.(3) The pathological change is lighter in group 2,3 and 4 compared with group 1,especially in the vicinity of the injured region.(4) GFAP and nestin expression increases in HBO therapy groups which is much more notable during 2w~4w after SCI,and group 4 shows a significant differnence.(5) Nerve-tract tracing indicates that the descending regeneration neuraxis increases in the distal end of injured region and peremeter of glial scar after HBO therapy.Conclusion:1)HBO therapy could relieve the pathological change after SCI,promote endogenous nerve stem or precusor cell proliferation,glial cell activation and neuraxis regeneration,thus to facilitate recovery of neurofuction after SCI.2) Combination of Hypobaric hypoxia preconditioning and immediately HBO treatment is effective in SCI prevention and cure.更多还原