Spinal implantation of hNT neurons and neuronal precursors: graft survival and functional effects in rats with ischemic spastic paraplegia

Transient spinal ischemia, a complication associated with aortic cross-clamp may lead to spastic paraplegia. Once fully developed this deficit is permanent. Quantitative histopathological assessments and pharmacological studies show that the ischemic spasticity is secondary to the loss of lumbar GABA and glycinergic inhibitory interneurons. In the present study, we investigated whether human hNT neurons or committed Sprague-Dawley rat spinal neuronal precursors (SNPs) when grafted into previously ischemic spinal segments depleted of inhibitory neurons would restore local inhibitory tone and ameliorate spasticity. Rats with functionally and electrophysiologically defined spasticity that received spinal graft of hNT neurons or neuronal precursors and immunosuppressive treatment displayed a progressive recovery of motor function that correlated with the improvement of otherwise exacerbated peripheral motor response evoked by stimulation of motor cortex. In contrast, in control, medium-injected or oligodendrocyte-grafted animals no significant therapeutic effect was seen. Stereological quantification of grafted neurons revealed 1-2% survival at three months after transplantation. These surviving neurons displayed a robust axo-dendritic sprouting and expression of markers typical of mature neurons including NSE, NeuN and synaptophysin. In both treatment groups a subpopulation of grafted neurons developed GABA immunoreactivity. These data provide evidence that a region specific grafting of hNT neurons or other neuronally committed cells, which have a potential to develop inhibitory neurotransmitter phenotype, represent an effective treatment modality to modulate ischemia-induced spastic paraplegia.     

Partial recovery after treatment of chronic paraplegia in rat

While acute spinal cord injury has been the object of intensive research, chronic spinal cord injury has received less attention although most clinical cases of spinal cord injury become chronic. We attempted to surgically "repair" chronic and acute spinal cord injury in a complete transection rat model using a multiple peripheral nerve grafting protocol. The lesion extent was assessed by magnetic resonance imaging (MRI) before the repair procedure. Rats were treated immediately after injury or at 2, 4, or 8 months postinjury. Standard behavioral methods were used to evaluate functional recovery. Two novel tests, the Bipedal Test and the Head-scratch test, were also employed to evaluate hindpaw positioning, interlimb coordination, and stepping rhythmicity, and to indicate rostrocaudal pathway regeneration. MRI helped guide the treatment procedure that was applied to animals with chronic injury. Treated animals demonstrated significant motor recovery. Axonal regeneration resultant to treatment was demonstrated histologically. The results suggest that not only acute but also chronic total paraplegia can be reversed to a moderate degree in rats with regard to hindlimb motor function.     

截瘫后经马尾骶神经根重建自控性膀胱功能

目的 通过对截瘫患马尾骶神经根的桥接来改善膀胱功能,建立起自控性膀胱。方法 将2例截瘫后患行切断15前根,两例行L5-S2前根的桥接。结果 2例患近期表现为膀胱容量增大,顺应性提高,远期有敲击跟腱后引发排尿．最大尿流率11．0mL/s。结论 建立“腱反射—脊髓中枢—膀胱”的人工反射弧途径来达到重建自控性膀胱功能是可行的。     

加味补阳还五汤治疗急性脊髓损伤的实验研究

为探讨加味补阳还五汤对实验性脊髓损伤的作用和机理,取健康SD大白鼠60只,随机分为中药高剂量组、中药低剂量组、尼莫地平组、假手术组和模型组,每组12只,采用改良Allen氏装置,以288g*cm-1能量造成T9～T11节段脊髓不完全损伤的动物模型.以脊髓神经功能(CBS计分)、运动诱发电位、辣根过氧化酶(HRP)示踪、组织形态学作为观察指标进行实验观察.结果显示中药组脊髓神经功能CBS值明显下降,运动诱发电位的波幅明显提高,脊髓轴浆运输能力改善,髓鞘、神经元细胞结构恢复理想.提示加味补阳还五汤可以阻止脊髓的继发性损伤,促进神经元及损伤神经纤维的修复.     

Fine mapping and genetic heterogeneity in the pure form of autosomal dominant familial spastic paraplegia

We evaluated seven families segregating pure, autosomal dominant familial spastic paraplegia (SPG) for linkage to four recently identified SPG loci on chromosomes 2q (1), 8q (2), 12q (3), and 19q (4). These families were previously shown to be unlinked to SPG loci on chromosomes 2p, 14q, and 15q. Two families demonstrated linkage to the new loci. One family (family 3) showed significant evidence for linkage to chromosome 12q, peaking at D12S1691 (maximum lod=3.22). Haplotype analysis of family 3 did not identify any recombinants among affected individuals in the 12q candidate region. Family 5 yielded a peak lod score of 2.02 at marker D19S868 and excluded linkage to other known SPG loci. Haplotype analysis of family 5 revealed several crossovers in affected individuals, thereby potentially narrowing the SPG12 candidate region to a 5-cM region between markers D19S868 and D19S220. Three of the families definitively excluded all four loci examined, providing evidence for further genetic heterogeneity of pure, autosomal dominant SPG. In conclusion, these data confirm the presence of SPG10 (chromosome 12), potentially reduce the minimum candidate region for SPG12 (chromosome 19q), and suggest there is at least one additional autosomal dominant SPG locus. Electronic Publication     

Somatostatin-like neurons are expressed in fetal neocortical homografts in adult rat spinal cord

Fetal central nervous system homografts to adult spinal cord are considered a potential aid for recovery of function after paraplegia. This study utilizes somatostatin (SOM) immunohistochemistry to study the organization of an embryonic day 14 (E14) neocortical homograft into the spinal cord of an adult host over 6 postoperative months. Although the E14 homograft does not contain SOM-positive cells, SOM-reactive neurons are expressed by 30 days postimplantation and are still present in 6-month-old homografts. SOM-immunoreactive neurons are bitufted or multipolar and have dendrites that are confined to the graft. The homograft contains SOM-immunoreactive axons entering and/or exiting from lamina II in the host dorsal horn and SOM-positive homografted neurons send axons into the host ventral columns. These data show that the SOM peptide neocortical phenotype is preserved in homografts to spinal cord but there is anatomical host-homograft integration.     

胸椎结核继发椎管内结核并截瘫

目的：探讨胸椎结核继发椎管内结核并截瘫的临床特点及治疗。方法：回顾性分析37例胸椎结核继发椎管内结核并截瘫患者的临床资料。结果：37例中有14例术前麻痹平面与椎体病变节段所致麻面不符，占38％。37例经病灶清除，椎管侧前方扩大减压术，将远至病变椎体节段上或下，到3个节段的椎管内结核肉芽，干酪物，炎性增生的较硬较厚的纤维组织从硬膜上剥脱干净，术后截瘫恢复率100％。结论：胸椎结核继发椎管内结核并截瘫，不仅是将压迫脊髓的死骨，残余坏死间盘，脓汁，干酪物清除。而充分的侧前方减压，剥脱干净硬膜外结核病变组织和瘢痕组织是截瘫治愈的关键。     

SPG11 – the most common type of recessive spastic paraplegia in Norway?

Background –  Hereditary spastic paraplegias (HSP) are neurodegenerative diseases mainly characterized by lower limb spasticity with additional neurological symptoms and signs in complicated forms. Among the many autosomal recessive forms, SPG11 appears to be one of the most frequent.
Objective –  Our objective was to select potential SPG11 patients based on phenotypes in our material, identify eventual disease-causing variants with the collaboration of laboratories abroad, estimate the frequency and spectrum of SPG11-mutations and describe their associated phenotypes.
Material and Methods –  Two isolated cases and two affected members of one family with cognitive impairment and confirmed thin corpus callosum on magnetic resonance imaging were selected from our database for inclusion into a multicenter study.
Results –  Mutations were found in the two isolated cases but not in the proband of the family. Conclusion – We present the first SPG11-HSP in the Norwegian population. SPG11 should be suspected in patients with isolated or recessive HSP, thin corpus callosum and mental retardation.     

Spastic paraplegia 15: Linkage and clinical description of three Tunisian families

Hereditary spastic paraplegias (HSP) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by slowly progressive spasticity of the lower limbs. The locus designated spastic paraplegia 15 (SPG15), located in a 16‐Mb interval on chromosome 14q, is associated with a rare autosomal recessive complicated form of HSP known as Kjellin's syndrome. In this study, we describe three additional families, of Tunisian origin, linked to the SPG15 locus, one of which had a significant multipoint LOD score of 3.46. In accordance with previous reports, the phenotype of our patients consisted of early onset spastic paraparesis associated with mental impairment and severe progression. Retinal degeneration was not observed, however, but we extended the phenotype of this form to include peripheral neuropathy and white matter abnormalities on MRI. Interestingly, like retinal degeneration, thin corpus callosum is not a constant feature in this entity. © 2007 Movement Disorder Society     

Effect of Electrical Anterior Sacral Nerve Root Stimulation on Pelvic Floor Function in Paraplegic Subjects

The effect of the Brindley stimulator on pelvic floor function has been studied in seven paraplegic subjects by standard manometric, radiologic, and electrophysiologic methods. There was no difference in the maximum resting pressure in the anal canal between the stimulated group and paraplegic subjects without sacral stimulators acting as controls. The fall in pressure in response to the rectosphinteric reflex as a percentage of the original resting pressure was significantly less, indicating a proportional effect on the external sphincter. There was less descent of the pelvic floor at rest in the stimulated group, but no difference in the pudendoanal reflex latency, motor unit potential duration, or resting electromyogram activity of the external anal sphincter. The maximum resting pressure in the anal canal, the pudendoanal reflex response amplitude, and the external anal sphincter electromyogram activity increased, however, with the duration of the implant. The S4 root had the dominant effect on the pelvic floor, with decreasing effects from the S3 and S2 roots on the pressure and integrated electromyogram activity generated by the external anal sphincter. The anorectal angle had not changed at rest in the group with the stimulator, but S4 root stimulation made it more acute than S3 or S2 root stimulation. The results suggest profound effects of S4 anterior root stimulation on the pelvic floor with additional effects of S3 and S2 anterior roots on pelvic function.