Enhanced motor cortex excitability after spinal cord injury

Transcranial magnetic stimulation（TMS）represents a useful non-invasive approach to studying cortical physiology,in addition to the descending motor pathways（Hallett,2000）,and may also be used to investigate the intracortical facilitatory and inhibitory mechanisms.

Supplementary motor area deactivation impacts the recovery of hand function from severe peripheral nerve injury

Although some patients have successful peripheral nerve regeneration,a poor recovery of hand function often occurs after peripheral nerve injury.It is believed that the capability of brain plasticity is crucial for the recovery of hand function.The supplementary motor area may play a key role in brain remodeling after peripheral nerve injury.In this study,we explored the activation mode of the supplementary motor area during a motor imagery task.We investigated the plasticity of the central nervous system after brachial plexus injury,using the motor imagery task.Results from functional magnetic resonance imaging showed that after brachial plexus injury,the motor imagery task for the affected limbs of the patients triggered no obvious activation of bilateral supplementary motor areas.This result indicates that it is difficult to excite the supplementary motor areas of brachial plexus injury patients during a motor imagery task,thereby impacting brain remodeling.Deactivation of the supplementary motor area is likely to be a serious problem for brachial plexus injury patients in terms of preparing,initiating and executing certain movements,which may be partly responsible for the unsatisfactory clinical recovery of hand function.

Protective effect of sodium valproate on motor neurons in the spinal cord following sciatic nerve injury in rats

BACKGROUND: Sodium valproate (VPA) is used to be an effective anti-epileptic drug. VPA possesses the characteristics of penetrating rapidly through the blood-brain barrier (BBB) and increasing levels of Bcl-2 and growth cone-associated protein (GAP) 43 in spinal cord. OBJECTIVE: To observe the effect of VPA on Bcl-2 expression and motor neuronal apoptosis in spinal cord of rats following sciatic nerve transection. DESIGN: Randomized controlled experiment. SETTING: Department of Hand Surgery and Microsurgery, Wuhan Puai Hospital. MATERIALS: A total of 30 male healthy SD rats of clean grade and with the body mass of 180-220 g were provided by Experimental Animal Center of Medical College of Wuhan University. Sodium Valproate Tablets were purchases from Hengrui Pharmaceutical Factory, Jiangsu. METHODS: The experiment was performed in the Central Laboratory of Wuhan Puai Hospital and Medical College of Wuhan University from February to May 2006. Totally 30 rats were randomly divided into two groups: treatment group (n =15) and model group (n =15). Longitudinal incision along backside of right hind limbs of rats was made to expose sciatic nerves, which were sharply transected 1 cm distal to the inferior margin of piriform muscle after nerve liberation under operation microscope to establish sciatic nerve injury rat models. Sodium Valproate Tablets were pulverized and diluted into 50 g/L suspension with saline. On the day of operation, the rats in the treatment group received 6 mL/kg VPA suspension by gastric perfusion, once a day, whereas model group received 10 mL/kg saline by gastric perfusion, once a day. L4-6 spinal cords were obtained at days 1, 4, 7, 14 and 28 after operation, respectively. Terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) technique and immunohistochemical method (SP method) were used to detect absorbance (A) of neurons with positive Bcl-2 expression. Apoptotic rate of cells (number of apoptotic cells/total number of cells×100%) was calculated. MAIN OUTCOME MEASURES: A value of neurons with positive Bcl-2 expression and apoptotic rate in spinal cord of rats in the two groups. RESULTS: A total of 30 SD rats were involved in the result analysis. ①expression of positive Bcl-2 neurons: A value of positive Bcl-2 neurons were 0.71±0.02, 0.86±0.04, 1.02±0.06 at days 4, 7 and 14, respectively after operation in the treatment group, which were obviously higher than those in the model group (0.62±0.03, 0.71±0.05, 0.89±0.04, t = 3.10-4.50, P < 0.05). ②apoptotic result of motor neurons: Apoptotic rate of motor neurons in spinal cord was (6.91±0.89)% and (15.12±2.34)% at days 7 and 14 in the treatment group, which was significantly lower than those in the model group [(9.45±1.61)%, (19.35±0.92)%, t = 2.39, 3.03. P < 0.05]. CONCLUSION: VPA can increase expression of Bcl-2 in spinal cord and reduce neuronal apoptosis in rats following sciatic nerve injury, and has protective effect on motor neuron in spinal cord of rats.

End-to-side neurorrhaphy repairs peripheral nerve injury：sensory nerve induces motor nerve regeneration

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve.It involves suturing the distal stump of the disconnected nerve（recipient nerve） to the side of the intimate adjacent nerve（donor nerve）.However,the motor-sensory specificity after end-to-side neurorrhaphy remains unclear.This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy.Thirty rats were randomized into three groups：（1） end-to-side neurorrhaphy using the ulnar nerve（mixed sensory and motor） as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve;（2） the sham group：ulnar nerve and cutaneous antebrachii medialis nerve were just exposed;and（3） the transected nerve group：cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied.At 5 months,acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group,and none of the myelinated axons were stained in either the sham or transected nerve groups.Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%.In contrast,no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment.These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.

Expression changes of nerve cell adhesion molecules L1 and semaphorin 3A after peripheral nerve injury

The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A m RNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration.

Effect of electroacupuncture on the mRNA and protein expression of Rho-A and Rho-associated kinase Ⅱ in spinal cord injury rats

Electroacupuncture is beneficial for the recovery of spinal cord injury, but the underlying mechanism is unclear. The Rho/Rho-associated kinase（ROCK） signaling pathway regulates the actin cytoskeleton by controlling the adhesive and migratory behaviors of cells that could inhibit neurite regrowth after neural injury and consequently hinder the recovery from spinal cord injury. Therefore, we hypothesized electroacupuncture could affect the Rho/ROCK signaling pathway to promote the recovery of spinal cord injury. In our experiments, the spinal cord injury in adult Sprague-Dawley rats was caused by an impact device. Those rats were subjected to electroacupuncture at Yaoyangguan（GV3）, Dazhui（GV14）, Zusanli（ST36） and Ciliao（BL32） and/or monosialoganglioside treatment. Behavioral scores revealed that the hindlimb motor functions improved with those treatments. Real-time quantitative polymerase chain reaction, fluorescence in situ hybridization and western blot assay showed that electroacupuncture suppressed the m RNA and protein expression of Rho-A and Rho-associated kinase Ⅱ（ROCKⅡ） of injured spinal cord. Although monosialoganglioside promoted the recovery of hindlimb motor function, monosialoganglioside did not affect the expression of Rho-A and ROCKⅡ. However, electroacupuncture combined with monosialoganglioside did not further improve the motor function or suppress the expression of Rho-A and ROCKⅡ. Our data suggested that the electroacupuncture could specifically inhibit the activation of the Rho/ROCK signaling pathway thus partially contributing to the repair of injured spinal cord. Monosialoganglioside could promote the motor function but did not suppress expression of Rho A and ROCKⅡ. There was no synergistic effect of electroacupuncture combined with monosialoganglioside.

Inhibition of Autophagy by Estradiol Promotes Locomotor Recovery after Spinal Cord Injury in Rats

17β-estradiol（E2） has been shown to have neuroprotective effects in different central nervous system diseases. The mechanisms underlying estrogen neuroprotection in spinal cord injury（SCI） remain unclear. Previous studies have shown that autophagy plays a crucial role in the course of nerve injury. In this study, we showed that E2 treatment improved the restoration of locomotor function and decreased the loss of motor neurons in SCI rats. Realtime PCR and western blot analysis revealed that the protective function of E2 was related to the suppression of LC3 II and beclin-1 expression. Immunohistochemical study further confirmed that the immunoreactivity of LC3 in the motor neurons was down-regulated when treated with E2. In vitro studies demonstrated similar results that E2 pretreatment decreased the autophagic activity induced by rapamycin（autophagy sensitizer） and increased viability in a PC12 cell model. These results indicated that the neuroprotective effects of E2 in SCI are partly related to the suppression of excessive autophagy.

Anterior subcutaneous transposition of the ulnar nerve improves neurological function in patients with cubital tunnel syndrome

Although several surgical procedures exist for treating cubital tunnel syndrome, the best surgical option remains controversial. To evaluate the efficacy of anterior subcutaneous transposition of the ulnar nerve in patients with moderate to severe cubital tunnel syndrome and to analyze prognostic factors, we retrospectively reviewed 62 patients（65 elbows） diagnosed with cubital tunnel syndrome who underwent anterior subcutaneous transposition. Preoperatively, the initial severity of the disease was evaluated using the Mc Gowan scale as modified by Goldberg： 18 patients（28%） had grade IIA neuropathy, 20（31%） had grade IIB, and 27（42%） had grade III. Postoperatively, according to the Wilson ＆ Krout criteria, treatment outcomes were excellent in 38 patients（58%）, good in 16（25%）, fair in 7（11%）, and poor in 4（6%）, with an excellent and good rate of 83%. A negative correlation was found between the preoperative Mc Gowan grade and the postoperative Wilson ＆ Krout score. The patients having fair and poor treatment outcomes had more advanced age, lower nerve conduction velocity, and lower action potential amplitude compared with those having excellent and good treatment outcomes. These results suggest that anterior subcutaneous transposition of the ulnar nerve is effective and safe for the treatment of moderate to severe cubital tunnel syndrome, and initial severity, advancing age, and electrophysiological parameters can affect treatment outcome.

Recording of spared motor evoked potentials and its augmentation by 4-aminopyridine in chronic spinal cord-injured rats

Objective To research the direct electrophysiological evidence of discomplete spinal cord injury (SCI) and the effect of 4-aminopyridine on it.Methods Motor evoked potentials (MEPs), both spinal cord recorded MEPs (scMEPs) and extracellularly recorded MEPs (exMEPs) were recorded and characterized on a T13 epidural electrode (scMEPs) and an extracellular microelectrode (exMEPs) for 10 normal rats and 40 rats with lesions of various severity (sham, 35?g*cm force (gcf), 70?gcf, 100?gcf impact injury) at the T8-T9 cord using the Allen's drop model. The incline plane and Tarlov techniques were used to assess clinical neurological function. Results MEPs in the normal rats were elicited by applying transcortical suprathreshold stimulation consisting of 3-4 early negative peaks (N1, N2, N3 and N4) followed by several late waves. The N1 and N2 peaks were largest in the anterior and ventrolateral funiculus, respectively, which was indicative of extrapyramidal pathways. The 100?gcf impact injuries and the cord transection abolished the MEP distal to the lesion, whereas the 35?gcf injuries resulted in a latency shift and amplitude decrement of the MEP peaks. Eighteen of the 20 rats with 70?gcf injuries showed clinical paraplegia. Among them, 7 rats had neurophysiological evidence of residual conduction pathways through the lesioned cord segment, such as the presence of N1 and N2 peaks in the scMEPs or exMEPs. After 4-aminopyridine (4-AP) administrations (1?mg/kg), the amplitude of the spared exMEP increased significantly and spread more widely. Conclusions MEPs evoked by transcortical stimulation travel mostly in the extrapyramidal tract. MEP monitoring could provide an excellent method of detecting the functional integrity of the motor tracts after SCI, and could even detect spared motor fibers after discomplete SCI. Furthermore, the use of 4-AP or other K+ channel blocking agents may be a potential treatment for patients with chronic moderate to severe SCI.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.