A combination therapy of neural and glial restricted precursor cells and chronic quipazine treatment paired with passive cycling promotes quipazine-induced stepping in adult spinalized rats

Abstract

Introduction

In order to develop optimal treatments to promote recovery from complete spinal cord injury (SCI), we examined the combination of: (1) a cellular graft of neural and glial restricted precursor (NRP/GRP) cells, (2) passive exercise, and (3) chronic quipazine treatment on behavioral outcomes and compared them with the individual treatment elements. NRP/GRP cells were transplanted at the time of spinalization.

Methods

Daily passive exercise began 1 week after injury to give sufficient time for the animals to recover. Chronic quipazine administration began 2 weeks after spinalization to allow for sufficient receptor upregulation permitting the expression of its behavioral effects. Behavioral measures consisted of the Basso, Beattie, and Bresnahan (BBB) locomotor score and percent of weight-supported steps and hops on a treadmill.

Results

Rats displayed an increased response to quipazine (BBB ≥ 9) beginning at 8 weeks post-injury in all the animals that received the combination therapy. This increase in BBB score was persistent through the end of the study (12 weeks post-injury).

Conclusion

Unlike the individual treatment groups which never achieved weight support, the combination therapy animals were able to perform uncoordinated weight-supported stepping without a body weight support system while on a moving treadmill (6.5 m per minute) and were capable of supporting their own weight in stance during open field locomotion testing. No regeneration of descending serotonergic projections into and through the lesion cavity was observed. Furthermore, these results are a testament to the capacity of the lumbar spinal cord, when properly stimulated, to sustain functioning locomotor circuitry following complete SCI.     

Understanding transition for youth with spinal cord injury: Youth and caregiver perceptions

Objective: The purpose of this study is to understand facilitators of and barriers to achieving positive transition results among youth with spinal cord injury (SCI), and to identify areas for intervention to improve transition outcomes.

Design: This study utilized qualitative methods and analysis was completed using Interpretive Phenomenological Analysis. Participants: Participants included adolescents (n?=?9, range?=?13–18 years old), young adults (n?=?14, range?=?22–30 years old) with an SCI, and their respective caregivers (n?=?17).

Results: The majority of participants had paraplegia (78%) and complete injuries (52%). The majority of caregivers were mothers (88%). Two primary themes were identified: Facilitators of Transition and Barriers to Transition. From these, five subthemes were developed for each category.

Conclusion: Youth with SCI and caregivers would benefit from organizations offering dynamic and progressive care options including social reintegration programs, peer-mentoring opportunities, and programs to teach individuals with SCI and families ways to develop motivation, resilience, and independent living skills. Last, better communication among healthcare providers and an increase of interdisciplinary and accessible adult healthcare facilities would foster greater transition successes for individuals with SCI.     

A combination therapy of neural and glial restricted precursor cells and chronic quipazine treatment paired with passive cycling promotes quipazine-induced stepping in adult spinalized rats

IntroductionIn order to develop optimal treatments to promote recovery from complete spinal cord injury (SCI), we examined the combination of: (1) a cellular graft of neural and glial restricted precursor (NRP/GRP) cells, (2) passive exercise, and (3) chronic quipazine treatment on behavioral outcomes and compared them with the individual treatment elements. NRP/GRP cells were transplanted at the time of spinalization.MethodsDaily passive exercise began 1 week after injury to give sufficient time for the animals to recover. Chronic quipazine administration began 2 weeks after spinalization to allow for sufficient receptor upregulation permitting the expression of its behavioral effects. Behavioral measures consisted of the Basso, Beattie, and Bresnahan (BBB) locomotor score and percent of weight-supported steps and hops on a treadmill.ResultsRats displayed an increased response to quipazine (BBB ≥ 9) beginning at 8 weeks post-injury in all the animals that received the combination therapy. This increase in BBB score was persistent through the end of the study (12 weeks post-injury).ConclusionUnlike the individual treatment groups which never achieved weight support, the combination therapy animals were able to perform uncoordinated weight-supported stepping without a body weight support system while on a moving treadmill (6.5 m per minute) and were capable of supporting their own weight in stance during open field locomotion testing. No regeneration of descending serotonergic projections into and through the lesion cavity was observed. Furthermore, these results are a testament to the capacity of the lumbar spinal cord, when properly stimulated, to sustain functioning locomotor circuitry following complete SCI.     

Changes in soleus muscle function and fiber morphology with one week of locomotor training in spinal cord contusion injured rats

The purpose of this study is two-fold: (1) to examine skeletal muscle function in a rat model of midthoracic contusion spinal cord injury (SCI) and (2) to evaluate the therapeutic influence of a short bout (1 week) of treadmill locomotor training on soleus muscle function (peak force, fatigability, contractile properties, fiber types), size (fiber area), and motor deficit and recovery (BBB scores) after SCI. The rats were injured with a moderate T8 spinal cord contusion and were assigned to either receive treadmill locomotor training (TM), starting 1 week after SCI for 5 consecutive days (20 min/trial, 2 trials/day) or not to receive any exercise intervention (no TM). Locomotor training resulted in a significant improvement in overall locomotor function (32% improvement in BBB scores) when compared to no TM. Also, the injured animals that trained for 1 week had 38% greater peak soleus tetanic forces (p < 0.05), a 9% decrease in muscle fatigue (p < 0.05), 23% larger muscle fiber CSA (p < 0.05), and decreased immunoexpression of fast heavy chain fiber types than did rats receiving no TM. In addition, there was a good correlation (0.704) between the BBB scores of injured animals and peak soleus muscle force regardless of group assignment. No significant differences were seen in twitch or time to peak tension values across groups. Collectively, these results indicate that 1 week of treadmill locomotor training, initiated early after SCI, can significantly improve motor recovery following SCI. The magnitude of these changes is remarkable considering the relatively short training interval and clearly illustrates the potential that initiating treadmill locomotor training shortly after injury may have on countering some of the functional deficits resulting from SCI.     

Weight change after spinal cord injury

Objectives: To study the patterns of weight change after spinal cord injury (SCI) and identify associated risk factors.

Study design: Cohort study.

Setting: Sixteen Spinal Cord Injury Model Systems (SCIMS), USA.

Participants: One thousand and ninety-four individuals with an SCI who were entered into the SCIMS and had a 1-year follow-up between October 2006 and November 2012.

Intervention: Not applicable.

Outcome measure: Change in body mass index (BMI) during the first year of injury. Height and weight were assessed during inpatient rehabilitation and 1 year after injury.

Results: Mean BMI decreased from 26.3 to 25.8?kg/m² during the first year after SCI (mean change: ?0.5?kg/m² (standard deviation: 3.58)). Weight loss was mainly observed among individuals classified as overweight or obese during rehabilitation (n = 576) with a BMI decrease of 1.4?kg/m², which varied significantly by sex, education, neurological level, and the presence of vertebral injury. Weight gain was noted among individuals classified as underweight or normal weight during rehabilitation (n?=?518) with a BMI increase of 0.5?kg/m², with the greatest increase among individuals of Hispanic origin (1.2?kg/m²), other marital status (1.2?kg/m²), age group 31–45 years (1.1?kg/m²), with less than high school education (1.1?kg/m²), without spinal surgery (0.9?kg/m²), and with motor functionally incomplete injury (0.8?kg/m²).

Conclusion: Our findings suggest that strategies for weight management should be addressed after a SCI to ameliorate the potential for unhealthful weight change, particularly among at-risk groups.     

“Low-intensity laser therapy effect on the recovery of traumatic spinal cord injury”

Scientific advances have been made to optimize the healing process in spinal cord injury. Studies have been developed to obtain effective treatments in controlling the secondary injury that occurs after spinal cord injury, which substantially changes the prognosis. Low-intensity laser therapy (LILT) has been applied in neuroscience due to its anti-inflammatory effects on biological tissue in the repairing process. Few studies have been made associating LILT to the spinal cord injury. The objective of this study was to investigate the effect of the LILT (GaAlAs laser—780 nm) on the locomotor functional recovery, histomorphometric, and histopathological changes of the spinal cord after moderate traumatic injury in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were used, which were divided into seven groups: control without surgery (n?=?3), control surgery (n?=?3), laser 6 h after surgery (n?=?5), laser 48 h after surgery (n?=?5), medullar lesion (n?=?5) without phototherapy, medullar lesion?+?laser 6 h after surgery (n?=?5), and medullar lesion?+?laser 48 h after surgery (n?=?5). The assessment of the motor function was performed using Basso, Beattie, and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The assessment of urinary dysfunction was clinically performed. After 21 days postoperative, the animals were euthanized for histological and histomorphometric analysis of the spinal cord. The results showed faster motor evolution in rats with spinal contusion treated with LILT, maintenance of the effectiveness of the urinary system, and preservation of nerve tissue in the lesion area, with a notorious inflammation control and increased number of nerve cells and connections. In conclusion, positive effects on spinal cord recovery after moderate traumatic spinal cord injury were shown after LILT.     

自噬蛋白p62在急性脊髓损伤大鼠脊髓组织中的表达

目的观察p62在早期急性脊髓损伤(SCI)模型大鼠脊髓组织中的表达变化,探讨p62在急性SCI的作用。方法将SD大鼠随机分为假手术组和造模后1、3、7、14 d组,每组6只。采用高空重物坠落击打方法造成大鼠SCI。采用Basso、Beattie、Bresnahan(BBB)评分法评估大鼠神经功能,取损伤的脊髓组织进行HE染色,观察病理学改变。通过实时荧光定量PCR、蛋白质印迹法和免疫组织化学方法检测急性SCI后大鼠脊髓组织中p62的表达变化。结果造模后1、3、7、14 d组BBB评分分别为(2.00±0.89)分、(4.67±1.03)分、(7.83±0.75)分、(14.50±1.05)分,均低于假手术组(21.00分),差异有统计学意义(P 0.05)。造模后1、3、7、14 d组损伤的脊髓组织神经元和白质髓鞘发生肿胀,随时间的延长逐渐出现变性和坏死。造模后1、3、7、14 d组p62表达逐渐增加,并呈持续增长趋势。结论 p62在大鼠发生急性SCI后表达持续增加,提示p62在急性SCI后发挥一定作用。     

Well on wheels intervention: Satisfaction with life and health for adults with spinal cord injuries

Objective/Background: To examine how demographic and injury characteristics identify satisfaction with life (SWL), and assess the differential effects of a wellness intervention by baseline SWL groups.

Design: Baseline and longitudinal analysis of a randomized controlled pilot intervention using decision tree regression and linear mixed models.

Setting: Community based.

Participants: Seventy-two individuals with spinal cord injury (SCI) were randomized to an intervention group (n?=?39) or control group (n?=?33). Participants were aged 44.1?±?13.0 years and 13.1?±?10.6 years post-injury. Most participants were male (n?=?50; 69.4%) and had paraplegia (n?=?38; 52.7%). Participants were classified as high versus low SWL at baseline using a cutoff score of 20.

Interventions: The intervention aimed to increase self-efficacy, and in turn, increase engagement in health-promoting behaviors related to SWL. Six 4-hour in-person workshops were conducted over a 3-month period led by experts and peer-mentors who were available for support.

Outcome measure(s): Self-efficacy for health practices, secondary condition severity, health-promoting behaviors, perceived stress, and SWL.

Results: At baseline, participants with low SWL were recently injured (<4.5 years), while persons with high SWL were married and younger (<49 years old). Intervention participants with low SWL at baseline significantly improved SWL over time compared to those with high SWL (P?=?0.02).

Conclusion: Certain injury and demographic characteristics were associated with SWL, and intervention participants with low SWL at baseline improved their SWL over 2 years. Healthcare providers should consider time post-injury, marital status, and age in identifying individuals at risk for low SWL that may benefit from wellness interventions.     

Beneficial effects of local profound hypothermia and the possible mechanism after experimental spinal cord injury in rats

Objective: The primary focus of this study was to investigate the effects of local profound hypothermia and to explore the possible mechanism in adult rats with spinal cord injury.

Study Design and Methods: Spinal cord injury models were established by placing aneurysm clips on T10. An epidural perfusion device was applied to maintain a steady temperature (18?°C) for 120?min with gradual rewarming to 37?°C Total hypothermic duration lasted up to about 170?min. The expression of axon regeneration inhibitors was tested by Western blot and real-time PCR. Luxol Fast Blue (LFB) stain and Bielschowsky silver stain were used to observe spinal cord morphology. Motor function of the hind limbs (BBB score) was monitored for 21 days.

Results: The expressions of RhoA, ROCK-II, NG2, Neurocan, Brevican, and Nogo-A were downregulated by regional hypothermia (RH) after spinal cord injury. Subsequent observation showed that rats that had received RH had an alleviated demyelinating condition and a greater number of nerve fibers. Furthermore, the RH group achieved higher BBB scores than the spinal cord injury (SCI) group.

Conclusions: Recovery of hind limb function in rats can be promoted by local profound hypothermia; this may be caused by the suppression of axon regeneration inhibitors.     

黄连素在脊髓损伤中对线粒体的保护作用及机制

目的探讨黄连素对脊髓损伤(SCI)后线粒体氧化损伤的作用和可能机制。方法将36只C57小鼠随机分为假手术组、SCI组(伤后立即腹腔注射10 mg/kg生理盐水)和黄连素组(SCI后立即腹腔注射10 mg/kg黄连素),每组12只。使用PSI-IH脊髓打击器建立小鼠SCI模型,于损伤后24 h处死小鼠,取脊髓组织。使用全自动酶标仪检测各组小鼠脊髓组织线粒体内丙二醛(MDA)、还原型谷胱甘肽(GSH)和超氧化物歧化酶(SOD)的变化;用蛋白质印迹法检测脊髓组织caspase-3、cleaved caspase-3的表达及细胞质内和线粒体内细胞色素C(Cyt C)的表达;用免疫荧光双标染色法检测脊髓组织中神经细胞凋亡情况。结果与假手术组相比,SCI组小鼠脊髓组织线粒体内MDA水平升高,GSH、SOD水平降低;细胞质内Cyt C和脊髓组织中caspase-3、cleaved caspase-3表达水平增高,线粒体内Cyt C表达水平降低;脊髓组织中神经元凋亡比例增高;差异均有统计学意义(P 0.05)。与SCI组相比,黄连素组小鼠脊髓组织线粒体内MDA水平降低,SOD和GSH水平增高;细胞质内Cyt C和脊髓组织中caspase-3、cleaved caspase-3表达水平降低,线粒体内Cyt C表达水平增高;脊髓组织中神经细胞凋亡比例减少;差异均有统计学意义(P 0.05)。结论黄连素可减轻SCI小鼠脊髓组织中神经细胞凋亡,这可能与其抑制线粒体氧化损伤、减少Cyt C释放、降低凋亡蛋白表达有关。     

同种异体骨髓间充质干细胞移植治疗大鼠脊髓损伤的时效性分析

目的：观察脊髓损伤后不同时间点骨髓间充质干细胞（bone mesenchymal stem cells,BMSCs）移植治疗后大鼠行为学变化、脊髓的病理改变及脑源性神经营养因子（brain—derived neurotrophic factor,BDNF）和神经生长因子（nervegrowthfactor,NGF）表达变化,探讨BMSCs的最佳移植时间。方法：80只健康成年SD大鼠随机分为8组,每组10只。A组为假损伤组,暴露胸10段脊髓但不造成冲击伤,B、C、D、E、F、G、H组以改良Allen法建立脊髓损伤模型。造模成功后,C、D、E、F、G、H组分别于损伤后0h、6h、24h、3d、5d和7d,将lxl0。体外培养的BMSCs用微量注射器注入于脊髓损伤局部,B组为单纯造模组,用等量细胞培养液代替。各组分别于损伤后1、2、4周进行脊髓运动功能BBB（Basso,Beattie,Bresnahan）运动学评分;分别取各组脊髓损伤组织0．5cm,制作HE染色病理切片,观察其形态学改变;Elisa法检测各组大鼠脊髓BDNF和NGF表达情况。结果：假手术组1、2、4周大鼠脊髓功能BBB评分均明显高于其余7组（P〈0．01）;术后l周细胞移植各组评分与单纯造模组相比差异无统计学意义（P〉0．05）;术后2周和4周细胞移植各组评分高于单纯造模组（P〈0．05）;损伤后2周BBB评分从高到低依次为F、E、G、D、H、C组,但6组组间比较差异无统计学意义（P〉0．05）;损伤后4周BBB评分,F组与其余5组（C,D,E,G,H组）比较差异有统计学意义（P〈0．05）,但其余5组组间差异无统计学意义（P〉O．05）。EUSA检测结果显示,F组BDNF和NGF含量均高于其他7组（P〈0．05）。大鼠脊髓标本切片HE染色,假手术组脊髓组织结构完整清楚,无中性粒细胞浸润;其余7组局部组织水肿明显,灰白质交界处模糊,周围可见不同程度胶质细胞增生及炎细胞浸润。结论：大鼠脊髓损伤后同种异体BMSCs移植对脊髓功能恢复有一定疗效,损伤后3d可能是BMSCs最佳移植时间。     

急性脊髓损伤脑脊液中炎性因子IL-6、IL-8的表达

目的了解急性脊髓损伤(SCI)后脑脊液中炎性因子白介素(IL)-6和IL-8的表达情况,探索其与SCI程度的关系。方法急性SCI患者31例,均在脊髓休克恢复后按Frankel分级进行神经功能评价,分为A级组4例、B级组7例、C级组12例、D级组8例。所有患者均在48 h内行手术减压植骨融合内固定治疗,随访6个月。在患者受伤后12、24、36、48、72 h行腰椎穿刺术并收集脑脊液,采用ELISA法检测IL-6和IL-8的浓度。结果 Frankel分级A级组1例死亡,3例神经功能无明显改善;其他组均有一定比例的患者神经功能改善。IL-6和IL-8在SCI早期(12 h)即出现高表达,且SCI越严重IL-6和IL-8升高越明显,损伤程度最严重的A级组IL-6和IL-8的表达分别为其他组的2.4~9.1倍和2.0~17.8倍;IL-6和IL-8的峰值分别在36 h和24 h;其中IL-6升高幅度更大、更持久,浓度变化大,且与SCI程度相关,损伤程度最严重的A级组IL-6在24、36、48 h的表达与12 h时的比值分别为3.6、5.6、4.7,而其他组的相应比值范围为0.74~2.40。结论急性SCI早期脑脊液中IL-6和IL-8浓度变化可在一定程度上作为判断SCI程度的指标,对帮助临床判断是否进行早期手术治疗有一定的参考价值。     

Protective effect of deferoxamine on experimental spinal cord injury in rat

Objective

To observe the protective effect of deferoxamine on experimental spinal cord injury (SCI) in rats.

Methods

Sprague-Dawley rats were randomly divided into the following four groups. Control group: rats were performed laminectomy only; SCI group: rats were performed laminectomy with SCI; DFO group: rats were injected intraperitoneally a bolus of 100 mg/kg deferoxamine after SCI; vehicle group: rats were injected intraperitoneally 0.9% saline after SCI. The SCI of animal model was made by using a modified Allen's method on T₁₀. Six rats of each group were sacrificed at 4 h after injured, and the levels of free iron and malondialdehyde (MDA) of involved spinal cord segments were measured by bleomycin assay and the thiobarbituric acid (TBA) separately. The recovery of function was assessed by Modified Tarlov's scale and inclined plane method at 7, 14, 21 d after SCI. The histologic changes of the damaged spinal cord were also examined at 7 d after SCI.

Results

Following SCI, the levels of free iron and MDA were increased significantly and the Modified Tarlov's score and inclined plane angles decreased in SCI group and vehicle group. In DFO group, the levels of free iron and MDA were not increased, but the Modified Tarlov's score and inclined plane angles decreased, the histological findings were improved as well.

Conclusion

Deferoxamine can reduce the levels of free iron and lipid peroxidation, and improve the hind limb functional status of rats with spinal cord injury.     

脊髓损伤后脂质蓄积对损伤灶自发荧光强度的影响

目的 :研究小鼠脊髓损伤后损伤灶的脂质蓄积与自发荧光强度之间的关系,探索硫酸铜能否消除脊髓损伤灶的自发荧光。方法:选取鼠龄8~12周,体重18~24 g的野生型小鼠36只,随机分为正常对照组(4只)与脊髓损伤组(32只)。脊髓损伤组于损伤后1、2、4、8周分别随机抽取8只处死,以损伤灶为中心取脊髓组织标本行冰冻切片(正常对照组取相同节段的脊髓,标本放入4%多聚甲醛溶液进行后固定),在荧光显微镜的绿色通道下观察自发荧光,进行油红O染色显示损伤灶的脂质蓄积,并分析自发荧光强度与脂质蓄积量的相关性。配制硫酸铜缓冲液处理切片以消除自发荧光,并优化硫酸铜浓度与作用时间。结果:正常脊髓组织切片未发现明显自发荧光或脂质染色,而脊髓损伤后在损伤灶出现自发荧光,并且强度随损伤后时间延长而增强。油红O染色显示损伤灶的脂质同样随伤后时间延长而蓄积,并且增长趋势与自发荧光的增强趋势呈正相关。应用硫酸铜缓冲液后,自发荧光强度显著降低,优化硫酸铜浓度与作用时间后效果更好。结论:脊髓损伤后损伤灶脂质蓄积可能在决定自发荧光的强度上起重要作用,自发荧光强度可以作为评估脂质过氧化损害的简便指标;优化的硫酸铜法能够显著消除脊髓损伤后损伤灶的自发荧光,有利于免疫荧光染色技术在脊髓损伤研究中的应用。     

大剂量甲基强的松龙对大鼠急性脊髓半切损伤的早期神经保护作用

目的研究大剂量甲基强的松龙（methylprednisolone,MP）对大鼠急性脊髓半切损伤的早期神经保护作用。方法 50只SD大鼠随机取10只仅行椎板切除,作为对照组。其余40只随机分为2组,脊髓半切损伤组及MP治疗组各20只。各组动物再随机平分为2个小组,分别在脊髓半切损伤后1d、7d进行BBB法神经功能评分、脊髓组织形态学观察、神经中丝（neurofilament NF）和胶质纤维酸性蛋白（glial fibrillary acidic protein,GFAP）免疫组化测定。结果脊髓半切损伤后立即使用大剂量MP明显提高了伤后7d时MP治疗组的BBB评分;对损伤脊髓的组织形态学有明显改善;明显提高了NF的表达,抑制了GFAP的表达。结论早期大剂量使用MP对大鼠急性脊髓半切损伤有神经保护作用。     

低剂量他克莫司治疗大鼠急性脊髓损伤的实验研究

目的：探讨低剂量他克莫司（tacrolimus，又名FK506）对大鼠急性脊髓损伤是否具有神经保护作用。方法：雄性Wistar大鼠72只，随机分为假手术组（12只）、损伤组（30只）和FK506治疗组（30只）。采用Allen’s打击法致伤大鼠T10脊髓，假手术组仅做椎板切除术。FK506治疗组在脊髓损伤后5min一次性经尾静脉注射FK5060．3mg／kg，其余两组以相同方法给予等量生理盐水。致伤后30min、6h、24h、48h、72h取伤段脊髓组织行病理观察及原位末端标记法（TUNEL）检测神经细胞凋亡，伤后1、3、7、14、21d行脊髓功能BBB评分和斜板实验。结果：伤后3、7、14、21d，FK506治疗组斜板实验和BBB评分明显优于损伤组，两组间比较差异有显著性（P〈0．05）；伤后各时间点FK506治疗组脊髓损伤区出血坏死较损伤组轻；伤后6、24、48、72h神经细胞凋亡FK506治疗组较损伤组明显减少，两组间比较差异有显著性（P〈0．05）。结论：在大鼠急性脊髓损伤后早期应用低剂量他克莫司（0．3mg/kg）治疗对神经具有保护作用，可减少神经细胞凋亡，减轻脊髓继发性损伤，促进脊髓功能恢复。     

胶质细胞源性神经营养因子对大鼠脊髓损伤后运动功能的影响

目的:研究胶质细胞源性神经营养因子（GDNF）对大鼠脊髓损伤后后肢运动功能恢复的影响。方法:采用改良Nystr(?)m法后路压迫大鼠胸段脊髓造成损伤模型,经蛛网膜下腔置管局部连续给予NGF （10μg/d）或GDNF（10μg/d）1周,对照组给予生理盐水。伤后4周3组分别观测:①伤段脊髓残存组织面积;②采用斜板试验和运动功能评分观察大鼠后肢运动功能恢复情况。结果:大鼠脊髓损伤后4～14d,GDNF治疗组后肢运动功能评分明显高于NGF组和生理盐水对照组（P<0.05）。伤后28d GDNF组伤段残存脊髓组织面积大于对照组和NGF组（P<0.01）。结论:外源性GDNF能减少脊髓损伤后伤区的坏死、萎缩并促进大鼠后肢运动功能的早期恢复。     

An ovine model of spinal cord injury

Objective: To develop a large animal model of spinal cord injury (SCI), for use in translational studies of spinal cord stimulation (SCS) in the treatment of spasticity. We seek to establish thresholds for the SCS parameters associated with reduction of post-SCI spasticity in the pelvic limbs, with implications for patients.

Study Design: The weight-drop method was used to create a moderate SCI in adult sheep, leading to mild spasticity in the pelvic limbs. Electrodes for electromyography (EMG) and an epidural spinal cord stimulator were then implanted. Behavioral and electrophysiological data were taken during treadmill ambulation in six animals, and in one animal with and without SCS at 0.1, 0.3, 0.5, and 0.9?V.

Setting: All surgical procedures were carried out at the University of Iowa. The gait measurements were made at Iowa State University.

Material and Methods: Nine adult female sheep were used in these institutionally approved protocols. Six of them were trained in treadmill ambulation prior to SCI surgeries, and underwent gait analysis pre- and post-SCI. Stretch reflex and H-reflex measurements were also made in conscious animals.

Results: Gait analysis revealed repeatable quantitative differences in 20% of the key kinematic parameters of the sheep, pre- and post-SCI. Hock joint angular velocity increased toward the normal pre-injury baseline in the animal with SCS at 0.9?V.

Conclusion: The ovine model is workable as a large animal surrogate suitable for translational studies of novel SCS therapies aimed at relieving spasticity in patients with SCI.     

Observation of locomotor functional recovery in adult complete spinal rats with BWSTT using semiquantitative and qualitative methods

STUDY DESIGN: Experimental rat model of spinal cord transection .SETTING: China rehabilitation research center. OBJECTIVE: To investigate locomotor functional recovery in spinal rats with BWSTT using semiquantitative and qualitative methods. METHODS: Five-day postoperative (dpo), adult female complete spinal rats (at T(8) level) received 40 days of body weight-supported treadmill training (BWSTT). Signs of functional recovery were examined with average combined scores (ACOS) and Basso Beattie and Bresnahan (BBB) scales at different time points. RESULTS: At 1-dpo, none of the spinal rats exhibited hindlimb movements. The spinal rats displayed functional progress with time, but the rare could recover to full weight-bearing hindlimb at 45-dpo. BBB and ACOS scores in the BWSTT group obtained better scores than those in the spinal cord injury (SCI) group at 30- and 45-dpo. Furthermore, all BBB and ACOS scores of spinal rats reached statistical significance between 7- and 30-dpo, and between 15- and 30-dpo. However, only ACOS but not BBB scores in the SCI and BWSTT groups showed statistics differences between 15- and 45-dpo, and between 30- and 45-dpo. The Spearman correlation coefficients of BBB and ACOS scores were 0.913 and 0.972 for the SCI and BWSTT groups, respectively. CONCLUSIONS: The results confirmed the existence of partial spontaneous hindlimb functional recovery in adult chronically spinal cord-transected rats, and that BWSTT can improve motor performance. In addition, our study suggests that qualitative and semiquantiative methods are strongly correlated with locomotor recovery in spinal rats, and the latter may be more sensitive in reflecting minor variance at different time points.     

Resection of glial scar following spinal cord injury

While many studies have focused on modulating the immune response and enhancing axonal regeneration after spinal cord injury (SCI), there is limited work being performed on evaluating the role of glial scar in SCI. We sought to evaluate the effects of glial scar resection in contusion models and dorsal hemisection models of SCI. At 1‐week postinjury, 2 mm of glial scar was excised from specimens in one of the two groups from each injury model. Functional outcome was measured weekly using the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale along with histologic evaluation of spinal cord tracts to determine axonal regeneration. Within the dorsal hemisection model, there was no significant difference in recovery for animals that underwent glial scar excision versus animals that did not have scar excision (p = 0.61). Animals subjected to the contusion model, however, demonstrated lower BBB scores in the glial resection group during the earlier postoperative periods (<4 weeks; p < 0.05). Histological analysis revealed no axons within the glial resection contusion model, and moderate axonal growth within the nonresection contusion group and both hemisection groups (p > 0.05 for differences among the three groups). While glial scar may serve to stabilize the preserved axonal tracts and thereby permit modest recovery in a contusion model of SCI, it may be of less importance with a dorsal hemisection model. These experiments highlight that basic biologic processes following SCI may vary tremendously based on the injury mechanism and that the role of glial scar in spinal cord regeneration must be elucidated. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 931–936, 2009