Control of membrane sealing in injured mammalian spinal cord axons

The process of sealing of damaged axons was examined in isolated strips of white matter from guinea pig spinal cord by recording the "compound membrane potential," using a sucrose-gap technique, and by examining uptake of horseradish peroxidase (HRP). Following axonal transection, exponential recovery of membrane potential occurred with a time constant of 20 +/- 5 min, at 37 degrees C, and extracellular calcium activity ([Ca(2+)](o)) of 2 mM. Most axons excluded HRP by 30 min following transection. The rate of sealing was reduced by lowering calcium and was effectively blocked at [Ca(2+)](o) 相似文献   

The critical role of voltage-dependent calcium channel in axonal repair following mechanical trauma

Membrane disruption following mechanical injury likely plays a critical role in the pathology of spinal cord trauma. It is known that intracellular calcium is a key factor that is essential to membrane resealing. However, the differential role of calcium influx through the injury site and through voltage dependent calcium channels (VDCC) has not been examined in detail. Using a well-established ex vivo guinea-pig spinal cord white matter preparation, we have found that axonal membrane resealing was significantly inhibited following transection or compression in the presence of cadmium, a non-specific calcium channel blocker, or nimodipine, a specific L-type calcium channel blocker. Membrane resealing was assessed by the changes of membrane potential and compound action potential (CAP), and exclusion of horseradish peroxidase 60 min following trauma. Furthermore, 1 microM BayK 8644, a VDCC agonist, significantly enhanced membrane resealing. Interestingly, this effect was completely abolished when the concentration of BayK 8644 was increased to 30 microM. These data suggest that VDCC play a critical role in membrane resealing. Further, there is likely an appropriate range of calcium influx through VDCC which ensures effective axonal membrane resealing. Since elevated intracellular calcium has also been linked to axonal deterioration, blockage of VDCC is proposed to be a clinical treatment for various injuries. The knowledge gained in this study will likely help us better understand the role of calcium in various CNS trauma, which is critical for designing new approaches or perhaps optimizing the effectiveness of existing methods in the treatment of CNS trauma.     

Temperature dependence of membrane sealing following transection in mammalian spinal cord axons

Using an in vitro sucrose-gap recording chamber, sealing of cut axons in isolated strips of white matter from guinea pig spinal cord was measured by recording the "compound membrane potential". This functional sealing was found to correlate well with anatomical resealing, measured by a horseradish peroxidase uptake assay. Near-complete functional and anatomical recovery of the axonal membrane occurred routinely within 60 min following transection at 37 degrees C in regular Krebs' solution. The rate of membrane potential recovery is exponential, with a time-constant of 20+/-5 min. The sealing process at 31 degrees C was similar to that at 37 degrees C, and was effectively blocked at 25 degrees C, under which condition most axons continued to take up horseradish peroxidase for more than 1h, and failed to substantially recover their membrane potential. Seventy-five percent of the cords transected at 40 degrees C had similar sealing behavior to those at 37 degrees C and 31 degrees C. The balance failed to seal the cut end. Two-dimensional morphometric analysis has shown that raising the temperature from 25 degrees C to above 31 degrees C significantly decreases axonal permeabilization to horseradish peroxidase (increases the sealing of transected ends) across all areas of a transverse section of spinal cord. Moreover, this enhancement of sealing exists across all axon calibers. Since severe cooling compromises membrane resealing, caution needs to be taken when hypothermic treatment (below 25 degrees C) is applied within the first 60 min following mechanical injury.In summary, we have found that at normal temperature (37 degrees C), nerve fibers repair their damaged membrane following physical injury with an hour. This is similar at mildly lower (31 degrees C) and relatively higher (40 degrees C) temperature, although some fibers tend to collapse under this febrile temperature. Moreover, severely low temperature (25 degrees C) hindered the repair of damaged membranes. Based on our study, caution is needed in treating spinal cord injury with low temperatures.     

Coupling of calcium homeostasis to axonal sodium in axons of mouse optic nerve

Axonal populations in neonatal and mature optic nerves were selectively stained with calcium dyes for analysis of calcium homeostasis and its possible coupling to axonal Na. Repetitive nerve stimulation causes a rise in axonal [Ca(2+)](i) the posttetanus recovery of which is impeded by increasing the number of action potentials in the tetanus. This effect is augmented in 4-aminopyridine (4-AP; 1 mM), which dramatically increases the calcium and presumably sodium load during the tetanus. Increasing axonal [Na](i) with the Na-ionophore monensin (4-50 microM) and ouabain (30 microM) retards posttetanus calcium decline, suggesting that efficient calcium clearance depends on a low level of axonal [Na](i). Posttetanus calcium clearance is not affected by K-mediated depolarization. To further examine coupling between axonal [Na](i) and [Ca(2+)](i), the resting axonal [Ca(2+)](i) was monitored as axonal [Na(+)](i) was elevated with ouabain, veratridine, and monensin. In all cases, elevation of axonal [Na(+)](i) evokes a calcium influx into axons. This influx is unrelated to activation of calcium channels but is consistent with calcium influx via reversal of the Na/Ca exchanger expected as a consequence of axonal [Na(+)](i) elevation. In conclusion, this study demonstrates that calcium homeostasis in the axons of the optic nerve is strongly coupled to axonal [Na(+)](i) in a manner consistent with the Na/Ca exchanger playing a major role in extruding calcium following nerve activity.     

The dynamics of axolemmal disruption in guinea pig spinal cord following compression

Membrane damage has been postulated as a critical factor in mediating axonal degeneration in brain and spinal cord trauma. Despite compelling evidence of membrane disruption as a result of physical insults in both in vivo and in vitro studies, the dynamics of such damage over the time post injury in in vivo studies has not been well documented. Using a well-characterized in vivo guinea pig spinal cord compression model and horseradish peroxidase exclusion assay, we have documented significant membrane disruption at 1 hr, 3 days, and 7 days following injury. Furthermore, the membrane damage was found to spread laterally 10 mm beyond the center of original compression site in both rostral and caudal directions. A second-degree polynomial fit of the measured data predicts a bilateral spread of approximately 20-21 mm of membrane disruption from the epicenter of injury over a period of about 20 days. Thus, this study shows that membrane damage exists days, and possibly weeks, after spinal cord trauma in live guinea pigs. This provides the evidence necessary to investigate the role of membrane damage in triggering axonal deterioration in the future. Furthermore, this study has also revealed a long therapeutical window for membrane repair and functional enhancement following traumatic injury in the central nervous system.     

Tissue calcium levels following spinal cord transection in rats

Adult rats were subjected to midthoracic spinal cord transections. Three segments of spinal cord, each approximately 5 mm in length, were removed from each animal at intervals from 5 min to 48 h postlesion; one from the lesion site and one each immediately rostral and caudal to the transection. Total tissue calcium concentrations ([Ca]t) for each spinal cord segment were determined using atomic absorption spectrophotometry and compared to control segments from untransected animals. [Ca]t levels in the segment at the lesion site was significantly elevated above control values at 30 min post-lesion, but decreased to control levels by 1 h. All other segments remained at control levels for the duration of the postlesion period. The rapid rise and fall of [Ca]t at the lesion site differs from spinal cord contusion studies in which [Ca]t remains at elevated levels for extended periods. It is postulated that the "open" transection injury permits the rapid clearance of calcium from the injury site.     

Expression of L-type calcium channel alpha(1)-1.2 and alpha(1)-1.3 subunits on rat sacral motoneurons following chronic spinal cord injury

In the presence of the monoamines serotonin and norepinephrine, motoneurons readily generate large persistent inward currents (PICs). The resulting plateau potentials amplify and sustain motor output. Monoaminergic input to the cord originates in the brainstem and the sharp reduction in monoamine levels that occurs following acute spinal cord injury greatly decreases motoneuron excitability. However, recent studies in the adult sacral cord of the rat have shown that motoneurons reacquire the ability to generate PICs and plateau potentials within 1-2 months following spinal transection. Ca(v)1.3 L-type calcium channels are involved in generating PICs in both healthy and injured animals. Additionally, expression of Ca(v)1.2 and Ca(v)1.3 L-type calcium channels is altered in several pathological conditions. Therefore, in this paper we analyzed the expression of L-type calcium channel alpha(1) subunits within the motoneuron pool following a complete transection of the spinal cord at the level of the sacral vertebra (S)2 segment. The analysis was done both caudally (S4 segment) and rostrally [thoracic vertebra (T)6 segment] from the injury site. The S4 segment was significantly reduced in diameter when compared with control animals, and this reduction was more evident in the white matter. Ca(v)1.2 alpha(1) subunit expression significantly increased (26%) in the motoneuron pool located caudally but not rostrally from the injury site. In contrast, the expression of Ca(v)1.3 alpha(1) subunit remained unchanged in both S4 and T6 segments. The differential expression of the two alpha(1) subunits in spinal injury suggests that Ca(v)1.2 and Ca(v)1.3 channels have different functions in neuronal adaptation following spinal cord injury.     

Ganglioside-induced regeneration and reestablishment of axonal continuity in spinal cord-transected rats

In this study we examined the effect of chronic GM-1 ganglioside treatment on the reestablishment of axonal continuity and functional recovery in spinal cord-transected rats. Previous studies have shown that chronic treatment with GM-1 ganglioside is effective in producing regeneration of lesioned mesostriatal dopaminergic neurons in the central nervous system [1, 2]. In addition, GM-1 ganglioside advances peripheral nerve regeneration following nerve crush injury [12]. Axonal continuity was determined by the ability of the spinal cord to transport horseradish peroxidase across the region of transection. Comparisons between ganglioside-treated and saline-treated controls showed that ganglioside treatment resulted in the reestablishment of axonal continuity between the spinal cord distal to the level of the transection and the brainstem. Saline-treated controls showed little evidence of axonal continuity between these two regions. Thus gangliosides induce reestablishment of axonal continuity and thereby could advance functional recovery in rats following spinal cord transection.     

Changes in the axonal membrane potential and Ca2+ concentration associated with peripheral nerve grafting after spinal cord injury

We performed peripheral nerve allografting in rats with spinal cord injury, and measured motor function and axonal membrane potential as well as Ca(2+) concentration of the nerve grafting spinal cord area by using a behavior observation system and a confocal laser-scanning microscope, respectively. In our experiments, we produced a model of peripheral nerve grafting after spinal cord injury by peripheral nerve allografting (sciatic nerve) in rats with spinal cord injury (thoracic cord hemisection). The group with spinal cord injury that underwent peripheral nerve grafting showed improvement in motor function, a significant increase in the axonal action potential, and a slight increase in the Ca(2+) concentration compared with the group that did not undergo nerve grafting.     

神经组织工程修复脊髓损伤的研究进展

由于脊髓损伤的重大影响,针对损伤后促进神经轴突的再生进行了大量的研究。作为一个新兴的迅速发展的领域,因能作为神经轴突生长的导向,组织工程已经受到了广泛的关注。众多的组织工程基质包括:支架材料、细胞和生物分子,其已经显示出支持轴突再生和促进功能恢复的潜力。就促进神经修复的支架材料、细胞、生物分子和目前治疗脊髓损伤的方法做一综述。     

Resealing of transected myelinated mammalian axons in vivo: evidence for involvement of calpain.

The mechanisms underlying resealing of transected myelinated rat dorsal root axons were investigated in vivo using an assay based on exclusion of a hydrophilic dye (Lucifer Yellow-biocytin conjugate). Smaller caliber axons (<5 microm outer diameter) resealed faster than larger axons. Resealing was Ca2+ dependent, requiring micromolar levels of extracellular [Ca2+] to proceed, and further accelerated in 1 mM Ca2+. Two hours after transection, 84% of axons had resealed in saline containing 2 mM Ca2+, 28% had resealed in saline containing no added Ca2+ and only 3% had resealed in the Ca2+ buffer BAPTA (3 mM). The enhancing effect of Ca2+ could be overcome by both non-specific cysteine protease inhibitors (e.g., leupeptin) and inhibitors specific for the calpain family of Ca2+ -activated proteases. Resealing in 2 mM Ca2+ was not inhibited by an inhibitor of phospholipase A2. Resealing in low [Ca2+] was not enhanced by agents which disrupt microtubules, but was enhanced by dimethylsulfoxide (0.5-5%). These results suggest that activation of endogenous calpain-like proteases by elevated intra-axonal [Ca2+] contributes importantly to membrane resealing in transected myelinated mammalian axons in vivo.     

Passive immunization with tenascin-R (TN-R) polyclonal antibody promotes axonal regeneration and functional recovery after spinal cord injury in rats

Tenascin-R (TN-R) is a neural specific protein and an important molecule involved in inhibition of axonal regeneration after spinal cord injury (SCI). Here we report on rabbit-derived TN-R polyclonal antibody, which acts as a TN-R antagonist with high titer and high specificity, promoted neurite outgrowth and sprouting of rat cortical neurons cultured on the inhibitory TN-R substrate in vitro. When locally administered into the lesion sites of rats received spinal cord dorsal hemisection, these TN-R antibodies could significantly decrease RhoA activation and improve functional recovery from corticospinal tract (CST) transection. Thus, passive immunotherapy with specific TN-R antagonist may represent a promising repair strategy following acute SCI.     

移植自聚合肽纳米纤维材料与RhoA-siRNA复合物修复脊髓损伤

背景：脊髓损伤后RhoA表达增高是神经再生困难的主要原因之一,本课题在前期研究证明自聚合肽纳米纤维材料能较好地促进脊髓损伤后结构与功能修复的基础上,构建了自聚合肽纳米纤维材料与RhoA-siRNA复合材料用于修复脊髓损伤。 目的：探讨自聚合肽纳米纤维材料介导siRNA干扰RhoA表达促进脊髓损伤修复。 方法：54只昆明小鼠随机数字表法分为4组。假手术组仅作脊髓暴露,其他3组在切除1 mm脊髓组织制备全横断脊髓损伤模型后,分别于损伤腔内填充生理盐水、自聚合肽纳米纤维支架或含有RhoA特异性siRNA复合物。通过FAM标记检测siRNA转染效率;免疫组化检测RhoA表达;免疫组化和定量分析检测再生神经纤维;行为学检测评定后肢功能恢复。 结果与结论：移植FAM标记的含有RhoA特异性siRNA复合物后,在脊髓内的神经纤维及大脑皮质运动区神经元胞体内均可检测到FAM荧光信号,提示siRNA可从复合材料中释放到组织中并成功导入靶细胞。与SAPNS组和生理盐水组相比,含有RhoA特异性siRNA复合物和自聚合肽纳米纤维支架组可显著降低RhoA在神经元的表达,提高脊髓损伤区内NF阳性神经纤维的密度,促进后肢功能的恢复。结果提示通过自聚合肽纳米纤维支架的介导,含有RhoA特异性siRNA复合物能有效干扰RhoA表达,从而促进脊髓损伤的修复。     

Emergence of highly neurofilament-immunoreactive zipper-like axon segments at the transection site in scalpel-cordotomized adult rats

Following transection of the spinal cord, severed axonal ends retract from the lesion site and attempt regeneration within 24 h of injury. Molecular mechanisms underlying such rapid axonal reactions after severance are not fully characterized so far. To better understand the early axonal degenerating and regenerating processes, we examined the immunohistological expression of axonal cytoskeletal proteins from 5 min to 48 h after scalpel-transection of adult rat spinal cord white matter. Within 30 min of transection, expression of neurofilament (NF)- and peripherin-like immunoreactivity (-IR) was enhanced in severed axonal ends, which conversely lost beta-III-tubulin-IR expression, indicating differential expression of beta-III-tubulin-IR and NF/peripherin-IR. During the next few hours, the strongly-NF/peripherin-IR-positive severed axonal ends adhered to each other and these cytoskeletal alterations expanded bi-directionally (rostro-caudally) 100-300 microm away from the transection point. Within 6 h of transection, secondary axotomy occurred at about 300 microm-rostral and -caudal to the primary transection point, which finally formed strongly-NF/peripherin-IR-positive zipper-like axon segments at the transection site. Notably, sprouting of secondarily severed axons was observed within 6 h of injury. The regenerative axons, which extended toward the transection site, could not traverse the transection site where the zipper-like axon segments resided. The zipper-like axon segments showed abnormal axolemmal permeability through the leakage of an axonal tracer. Western blot analysis revealed a slight increase in peripherin content in transected spinal cord. Local treatment with cycloheximide suppressed the axotomy-induced peripherin-IR-enhancement in severed ends, suggesting the occurrence of intra-axonal peripherin synthesis in vivo. Treatment with calpain inhibitors frequently formed abnormally swollen microtubule-free ends, which suggests that calpain-activation is critical for functional growth cone formation in adult rat spinal cord. These observations indicate that adult rat cordotomy with a scalpel results in the rapid formation of intensely NF-IR-positive zipper-like axon segments at the transection site, which are similar to "preserved fibers" reported by Ramon y Cajal [Ramon y Cajal S (1928) Degeneration and regeneration in the nervous system. New York: Hafner]. On the other hand, axonal regenerative responses start within 6 h of injury, which may be supported by calpain-activation and intra-axonal protein synthesis.     

Matrix inclusion within synthetic hydrogel guidance channels improves specific supraspinal and local axonal regeneration after complete spinal cord transection

We have previously shown that a novel synthetic hydrogel channel composed of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (pHEMA-MMA) is biocompatible and supports axonal regeneration after spinal cord injury. Our goal was to improve the number and type of regenerated axons within the spinal cord through the addition of different matrices and growth factors incorporated within the lumen of the channel. After complete spinal cord transection at T8, pHEMA-MMA channels, having an elastic modulus of 263+/-13 kPa were implanted into adult Sprague Dawley rats. The channels were then filled with one of the following matrices: collagen, fibrin, Matrigel, methylcellulose, or smaller pHEMA-MMA tubes placed within a larger pHEMA-MMA channel (called tubes within channels, TWC). We also supplemented selected matrices (collagen and fibrin) with neurotrophic factors, fibroblast growth factor-1 (FGF-1) and neurotrophin-3 (NT-3). After channel implantation, fibrin glue was applied to the cord-channel interface, and a duraplasty was performed with an expanded polytetrafluoroethylene (ePTFE) membrane. Controls included animals that had either complete spinal cord transection and implantation of unfilled pHEMA-MMA channels or complete spinal cord transection. Regeneration was assessed by retrograde axonal tracing with Fluoro-Gold, and immunohistochemistry with NF-200 (for total axon counts) and calcitonin gene related peptide (CGRP, for sensory axon counts) after 8 weeks survival. Fibrin, Matrigel, methylcellulose, collagen with FGF-1, collagen with NT-3, fibrin with FGF-1, and fibrin with NT-3 increased the total axon density within the channel (ANOVA, p<0.05) compared to unfilled channel controls. Only fibrin with FGF-1 decreased the sensory axon density compared to unfilled channel controls (ANOVA, p<0.05). Fibrin promoted the greatest axonal regeneration from reticular neurons, and methylcellulose promoted the greatest regeneration from vestibular and red nucleus neurons. With Matrigel, there was no axonal regeneration from brainstem motor neurons. The addition of FGF-1 increased the axonal regeneration of vestibular neurons, and the addition of NT-3 decreased the total number of axons regenerating from brainstem neurons. The fibrin and TWC showed a consistent improvement in locomotor function at both 7 and 8 weeks. Thus, the present study shows that the presence and type of matrix contained within synthetic hydrogel guidance channels affects the quantity and origin of axons that regenerate after complete spinal cord transection, and can improve functional recovery. Determining the optimum matrices and growth factors for insertion into these guidance channels will improve regeneration of the injured spinal cord.     

胶质细胞源性神经营养因子缓释微球及NogoA,ChABC缓释微球联合应用损伤脊髓再生的形态学变化

背景：促进轴突再生的原则是改善抑制再生的环境和提高轴突生长能力,措施主要有轴突生长抑制因子阻滞剂和神经营养因子应用。用可降解微球加载药物是一种在局部提供持续药物释放的方法。 目的：探讨胶质细胞源性神经营养因子、NogoA、ChABC 缓释微球联合应用促进大鼠损伤脊髓再生病理形态学修复的作用。 方法：建立SD大鼠T10 脊髓完全横断伤模型,分别在损伤局部给予生理盐水、胶质细胞源性神经营养因子、胶质细胞源性神经营养因子缓释微球、NogoA缓释微球、ChABC 缓释微球及3种微球联合治疗,并设立未造模的正常组及假手术组。损伤后10周,每组行四甲基若丹明葡聚糖胺顺行示踪,及神经丝蛋白200、生长相关蛋白43、胶质细胞源性神经营养因子免疫组化检查,并采用免疫组化图像分析系统进行定量分析。 结果与结论：胶质细胞源性神经营养因子、NogoA、ChABC 缓释微球联合能提高脊髓损伤局部神经丝蛋白200、生长相关蛋白43、胶质纤维酸性蛋白的表达水平,显示局部脊髓再生修复加强,其效果优于单用胶质细胞源性神经营养因子缓释微球。提示,胶质细胞源性神经营养因子缓释微球及NogoA,ChABC 缓释微球联合促大鼠损伤脊髓再生修复其效果优于单用胶质细胞源性神经营养因子缓释微球。     

Serotonin facilitates a persistent calcium current in motoneurons of rats with and without chronic spinal cord injury

In the months after spinal cord transection, motoneurons in the rat spinal cord develop large persistent inward currents (PICs) that are responsible for muscle spasticity. These PICs are mediated by low-threshold TTX-sensitive sodium currents (Na PIC) and L-type calcium currents (Ca PIC). Recently, the Na PIC was shown to become supersensitive to serotonin (5-HT) after chronic injury. In the present paper, a similar change in the sensitivity of the Ca PIC to 5-HT was investigated after injury. The whole sacrocaudal spinal cord from acute spinal rats and spastic chronic spinal rats (S2 level transection 2 mo previously) was studied in vitro. Intracellular recordings were made from motoneurons and slow voltages ramps were applied to measure PICs. TTX was used to block the Na PIC. For motoneurons of chronic spinal rats, a low dose of 5-HT (1 microM) significantly lowered the threshold of the Ca PIC from -56.7 +/- 6.0 to -63.1 +/- 7.1 mV and increased the amplitude of the Ca PIC from 2.4 +/- 1.0 to 3.0 +/- 0.73 nA. Higher doses of 5-HT acted similarly. For motoneurons of acute spinal rats, low doses of 5-HT had no significant effects, whereas a high dose (about 30 microM) significantly lowered the threshold of the L-Ca PIC from -58.5 +/- 14.8 to -62.5 +/- 3.6 mV and increased the amplitude of the Ca PIC from 0.69 +/- 1.05 to 1.27 +/- 1.1 nA. Thus Ca PICs in motoneurons are about 30-fold supersensitive to 5-HT in chronic spinal rats. The 5-HT-induced facilitation of the Ca PIC was blocked by nimodipine, not by the I(h) current blocker Cs(+) (3 mM) or the SK current blocker apamin (0.15 microM), and it lasted for hours after the removal of 5-HT from the nCSF, even increasing initially after removing 5-HT. The effects of 5-HT make motoneurons more excitable and ultimately lead to larger, more easily activated plateaus and self-sustained firing. The supersensitivity to 5-HT suggests the small amounts of endogenous 5-HT below the injury in a chronic spinal rat may act on supersensitive receptors to produce large Ca PICs and ultimately enable muscle spasms.     

Recovery of locomotion correlated with axonal regeneration after a complete spinal transection in the eel.

This research has examined the relationship between axonal regeneration and the return of normal movement following complete transection of the spinal cord. We made measurements of tail beat frequency and amplitude of the caudal body wave from video recordings of eels (Anguilla anguilla) swimming in a water tunnel at several speeds. Each eel was then anaesthetised and the spinal cord cut caudal to the anus; in some animals the resulting gap was filled with a rubber block. All animals were kept at 25 degrees C for recovery periods ranging from 7 to 128 days, during which their swimming performance was monitored regularly. Each fish was then re-anaesthetised and perfused with fixative and the regrowing descending axons labelled with 1,1'-diotadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate.For all animals and at all speeds after surgery, tail beat frequency increased, while amplitude decreased. In non-blocked animals, an improvement in performance was first seen from 8 days following transection and thereafter tail beat frequency decreased progressively until it had returned to normal after 35 to 45 days, while amplitude remained below baseline until at least 45 days. In these animals, few axonal growth cones had penetrated the caudal stump by 7 days, but some had extended as much as 3 mm by 15 days. Many had reached as far as 6 mm between 25 and 36 days, while by 128 days they had progressed up to 10.5 mm. Contralateral crossing was never observed. Functional recovery was never witnessed in animals in which the cord had been blocked and these eels swam at all times with elevated tail beat frequency and reduced caudal amplitude. No labelled axons could be traced into the caudal spinal cord at any recovery stage in such animals.We conclude that re-innervation of only 1-2 segments caudal to the injury is necessary for functional recovery, although continued axonal growth may be important for the refinement of some aspects of movement.     

神经营养因子对脊髓损伤修复作用研究进展

脊髓损伤(SCI)是一种严重的神经系统创伤,后果严重常导致患者不同程度地瘫痪和大小便障碍,其致残率与耗费高给家庭及社会造成严重的负担.因此研究脊髓组织损伤后的再生和修复具有重要的现实意义.大量实验研究表明神经营养因子对脊髓损伤后的神经组织修复过程有重要作用.就这一领域新的研究进展作一综述.     

建立脊髓横断模型大鼠的系统评价

背景：建立一种成功率较高、安全可靠的标准脊髓横断模型是研究脊髓修复的前提条件。目的：评价大鼠脊髓横断模型制备的价值及椎板切除对脊髓的影响。方法：检索美国国立医学图书馆(PubMed)、中国知网(CNKI)、重庆维普(VIP)、万方数据库中所用关于大鼠脊髓横断模型的随机对照研究。结果与结论：11篇随机对照研究符合纳入标准(英文2篇,中文9篇),共394只大鼠纳入研究,脊髓半横断组与椎板切除组1-6周内下肢运动功能评分(BBB评分)、4周内电生理差异有显著性意义(WMD=-12.86,95%CI-16.10至-9.62,P < 0.01)、(WMD=15.36,95%CI 11.36-19.36,P < 0.01),半横断组6周后BBB评分差异无显著性意义(WMD=-10.28;95%CI -24.20-3.64;P=0.15);脊髓全横断组与椎板切除组1-6周内BBB评分、4周内电生理差异有显著性意义(WMD=-18.83,95%CI -20.64至-17.01,P < 0.01)、(WMD= -11.21,95%CI -16.35至-6.08,P < 0.01)。椎板切除组与正常组4周内BBB评分与电生理评分差异无显著性意义(WMD=-0.00,95%CI -0.01-0.01,P=1)、(WMD= 0.43,95%CI -0.35-1.21,P=0.28);大鼠脊髓横断组和椎板切除组死亡数差异无显著性意义(RD=0.05,95%CI -0.03-0.13;P=0.26)。说明脊髓横断法是一种稳定性好、可复制性强、存活率高的脊髓损伤研究模型,但其横断的准确性、术后护理及对照组的设立有待商榷。中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程