右正中神经电刺激对重型颅脑损伤患者脑血流灌注影响的SPECT-CT观察

目的研究SPECT-CT融合机检测重型颅脑损伤昏迷患者行右正中神经电刺激前后脑血流灌注变化情况。方法选择我院重型颅脑损伤患者50例作为研究对象,伤后2周持续昏迷,接受右正中神经电刺激治疗。治疗前后7 d均进行SPECT-CT检查,评价脑血流灌注变化的情况。利用MATLAB和SPM软件对检测结果进行分析处理,得到昏迷患者的脑皮层血流及健康成人的比较值,使用区域分析法进行脑皮层分析,丘脑及脑干部位的血流灌注增加特征变化,利用图形重建迭加技术获得脑表面血流灌注增加值.并测量GCS和GOS评分,伤后1年作GOS预后评估。结果电刺激治疗后,患者脑血流有明显改善,血流灌注增加表现,GOS评分较电刺激后评分升高。结论右正中神经电刺激技术可以改善脑干血流灌注状况。     

高压氧及右正中神经电刺激对重型颅脑外伤患者的术后催醒作用

目的 探讨高压氧(HBO)及右正中神经电刺激(RMNS)对重型颅脑损伤患者术后催醒的影响. 方法 选择83例术后恢复期重型颅脑损伤患者,按随机数字表法分为治疗组(n=42)和对照组(n=41),其中对照组患者接受常规及对症治疗,治疗组在此基础上同时进行高压氧(HBO)及右正中神经电刺激(RMNS)治疗.3个月后比较2组患者的格拉斯哥昏迷评分(GCS)、格拉斯哥预后评分(GOS)、日常生活能力评分(ADL)、神经功能缺损评定(ESS)和远期生活质量评分(KPS),采用经颅三维多普勒彩色超声(TCD)和脑地形图(BEAM)分别评定脑血流量和脑电活动的变化. 结果与对照组比较,治疗组患者治疗1、3个月时各项评分均有改善,差异有统计学意义(P＜0.05);TCD检查显示治疗组患者病灶局部脑血流量明显提高,对照组仅有17例患者病灶局部脑血流量较前有所提高;与对照组比较,BEAM显示治疗组患者治疗后弥漫性慢波明显减少. 结论 高压氧及右正中神经电刺激治疗能促进重型颅脑损伤患者脑组织和脑神经功能的恢复,促进意识水平的改善.     

Femoral nerve regeneration and its accuracy under different injury mechanisms

Surgical accuracy has greatly improved with the advent of microsurgical techniques. However, complete functional recovery after peripheral nerve injury has not been achieved to date. The mechanisms hindering accurate regeneration of damaged axons after peripheral nerve injury are in urgent need of exploration. The present study was designed to explore the mechanisms of peripheral nerve regeneration after different types of injury. Femoral nerves of rats were injured by crushing or freezing. At 2, 3, 6, and 12 weeks after injury, axons were retrogradely labeled using 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate(Dil) and True Blue, and motor and sensory axons that had regenerated at the site of injury were counted. The number and percentage of Dil-labeled neurons in the anterior horn of the spinal cord increased over time. No significant differences were found in the number of labeled neurons between the freeze and crush injury groups at any time point. Our results confirmed that the accuracy of peripheral nerve regeneration increased with time, after both crush and freeze injury, and indicated that axonal regeneration accuracy was still satisfactory after freezing, despite the prolonged damage.     

Electrical stimulation of the vagus nerve protects against cerebral ischemic injury through an anti-infammatory mechanism

Vagus nerve stimulation exerts protective effects against ischemic brain injury; however, the underlying mechanisms remain unclear. In this study, a rat model of focal cerebral ischemia was established using the occlusion method, and the right vagus nerve was given electrical stimulation (constant current of 0.5 mA; pulse width, 0.5 ms; frequency, 20 Hz; duration, 30 seconds; every 5 minutes for a total of 60 minutes) 30 minutes, 12 hours, and 1, 2, 3, 7 and 14 days after surgery. Electrical stimulation of the vagus nerve substantially reduced infarct volume, improved neurological function, and decreased the expression levels of tumor necrosis factor-α and interleukin-6 in rats with focal cerebral ischemia. The experimental findings indicate that the neuroprotective effect of vagus nerve stimulation following cerebral ischemia may be associated with the inhibition of tumor necrosis factor-α and interleukin-6 expression.     

Electrical stimulation does not enhance nerve regeneration if delayed after sciatic nerve injury: the role of fibrosis

Electrical stimulation has been shown to accelerate and enhance nerve regeneration in sensory and motor neurons after injury, but there is little evidence that focuses on the varying degrees of fibrosis in the delayed repair of peripheral nerve tissue. In this study, a rat model of sciatic nerve transection injury was repaired with a biodegradable conduit at 1 day, 1 week, 1 month and 2 months after injury, when the rats were divided into two subgroups. In the experimental group, rats were treated with electrical stimuli of frequency of 20 Hz, pulse width 100 ms and direct current voltage of 3 V; while rats in the control group received no electrical stimulation after the conduit operation. Histological results showed that stained collagen fibers comprised less than 20% of the total operated area in the two groups after delayed repair at both 1 day and 1 week but after longer delays, the collagen fiber area increased with the time after injury. Immunohistochemical staining revealed that the expression level of transforming growth factor β(an indicator of tissue fibrosis) decreased at both 1 day and 1 week after delayed repair but increased at both 1 and 2 months after delayed repair. These findings indicate that if the biodegradable conduit repair combined with electrical stimulation is delayed, it results in a poor outcome following sciatic nerve injury. One month after injury, tissue degeneration and distal fibrosis are apparent and are probably the main reason why electrical stimulation fails to promote nerve regeneration after delayed repair.     

Nonpharmacological, somatic treatments of depression: electroconvulsive therapy and novel brain stimulation modalities

Until recently, a review of nonpharmacological, somatic treatments of psychiatric disorders would have included only electroconvulsive therapy (ECT). This situation is now changing very substantially. Although ECT remains the only modality in widespread clinical use, several new techniques are under investigation. Their principal indication in the psychiatric context is the treatment of major depression, but other applications are also being studied. All the novel treatments involve brain stimulation, which is achieved by different technological methods. The treatment closest to the threshold of clinical acceptability is transcranial magnetic stimulation (TMS). Although TMS is safe and relatively easy to administer, its efficacy has still to be definitively established. Other modalities, at various stages of research development, include magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). We briefly review the development and technical aspects of these treatments, their potential role in the treatment of major depression, adverse effects, and putative mechanism of action. As the only one of these treatment modalities that is in widespread clinical use, more extended consideration is given to ECT Although more than half a century has elapsed since ECT was first introduced, it remains the most effective treatment for major depression, with efficacy in patients refractory to antidepressant drugs and an acceptable safety profile. Although they hold considerable promise, the novel brain stimulation techniques reviewed here will be need to be further developed before they achieve clinical acceptability.     

Pulsed electrical stimulation protects neurons in the dorsal root and anterior horn of the spinal cord after peripheral nerve injury

Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 m A and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers.     

Structural and functional connectivity in traumatic brain injury

Traumatic brain injury survivors often experience cognitive deficits and neuropsychiatric symptoms.However,the neurobiological mechanisms underlying specific impairments are not fully understood.Advances in neuroimaging techniques(such as diffusion tensor imaging and functional MRI)have given us new insights on structural and functional connectivity patterns of the human brain in both health and disease.The connectome derived from connectivity maps reflects the entire constellation of distributed brain networks.Using these powerful neuroimaging approaches,changes at the microstructural level can be detected through regional and global properties of neuronal networks.Here we will review recent developments in the study of brain network abnormalities in traumatic brain injury,mainly focusing on structural and functional connectivity.Some connectomic studies have provided interesting insights into the neurological dysfunction that occurs following traumatic brain injury.These techniques could eventually be helpful in developing imaging biomarkers of cognitive and neurobehavioral sequelae,as well as predicting outcome and prognosis.     

Bacterial melanin promotes recovery after sciatic nerve injury in rats

Bacterial melanin, obtained from the mutant strain of Bacillus Thuringiensis, has been shown to promote recovery after central nervous system injury. It is hypothesized, in this study, that bacterial melanin can promote structural and functional recovery after peripheral nerve injury. Rats subjected to sciatic nerve transection were intramuscularly administered bacterial melanin. The sciatic nerve transected rats that did not receive intramuscular administration of bacterial melanin served as controls. Behavior tests showed that compared to control rats, the time taken for instrumental conditioned reflex recovery was significantly shorter and the ability to keep the balance on the rotating bar was significantly better in bacterial melanin-treated rats. Histomorphological tests showed that bacterial melanin promoted axon regeneration after sciatic nerve injury. These findings suggest that bacterial melanin exhibits neuroprotective effects on injured sciatic nerve, contributes to limb motor function recovery, and therefore can be used for rehabilitation treatment of peripheral nerve injury.     

Biological conduit small gap sleeve bridging method for peripheral nerve injury: regeneration law of nerve fibers in the conduit

The clinical effects of 2-mm small gap sleeve bridging of the biological conduit to repair peripheral nerve injury are better than in the traditional epineurium suture, so it is possible to replace the epineurium suture in the treatment of peripheral nerve injury. This study sought to identify the regeneration law of nerve fibers in the biological conduit. A nerve regeneration chamber was constructed in models of sciatic nerve injury using 2-mm small gap sleeve bridging of a biodegradable biological conduit. The results showed that the biological conduit had good histocompatibility. Tissue and cell apoptosis in the conduit apparently lessened, and regenerating nerve fibers were common. The degeneration regeneration law of Schwann cells and axons in the conduit was quite different from that in traditional epineurium suture. During the prime period for nerve fiber regeneration(2–8 weeks), the number of Schwann cells and nerve fibers was higher in both proximal and distal ends, and the effects of the small gap sleeve bridging method were better than those of the traditional epineurium suture. The above results provide an objective and reliable theoretical basis for the clinical application of the biological conduit small gap sleeve bridging method to repair peripheral nerve injury.     

Use of nerve elongator to repair short-distance peripheral nerve defects: a prospective randomized study

Repair techniques for short-distance peripheral nerve defects, including adjacent joint flexion to reduce the distance between the nerve stump defects, nerve splint suturing, and nerve sle eve connection, have some disadvantages. Therefore, we designed a repair technique involving intraoperative tension-free application of a nerve elongator and obtained good outcomes in the repair of short-distance peripheral nerve defects in a previous animal study. The present study compared the clinical outcomes between the use of this nerve elongator and performance of the conventional method in the repair of short-distance transection injuries in human elbows. The 3-, 6-, and 12-month postoperative follow-up results demonstrated that early neurological function recovery was better in the nerve elongation group than in the conventional group, but no significant difference in long-term neurological function recovery was detected between the two gro ups. In the nerve elongation group, the nerves were sutured without tension, and the duration of postoperative immobilization of the elbow was decreased. Elbow function rehabilitation was significantly better in the nerve elongation group than in the control group. Moreover, there were no security risks. The results of this study confirm that the use of this nerve elongator for repair of short-distance peripheral nerve defects is safe and effective.     

Stability of rat models of fluid percussion-induced traumatic brain injury: comparison of three different impact forces

Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm(101.32 ± 11.16 k Pa), 2.6 ± 0.16 atm(263.44 ± 16.21 k Pa), and 3.6 ± 0.16 atm(364.77 ± 16.21 k Pa), respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.     

右正中神经电刺激对颅脑创伤昏迷患者脑血流灌注的影响:SPECT-CT显像观察

目的 利用SPECT - CT融合机脑血流灌注显像技术检测重型颅脑创伤昏迷患者行右正中神经电刺激前后脑血流灌注变化情况.方法 重型颅脑损伤患者32例,伤后2周仍昏迷,接受右正中神经电刺激治疗.治疗前及治疗第7天,行SPECT - CT评价脑血流灌注变化情况.利用MATLAB和SPM软件对检测结果进行分析处理,得到昏迷患者脑皮层丘脑血流与健康成人比较值,用区域分析法分析脑皮层、丘脑和脑干部位的血流灌注增加的特征改变,利用图像重建迭加技术获得脑表面(含颅底面)血流灌注增加值.结果 颅脑创伤昏迷患者与健康成人相比较,其感觉运动皮层、双侧丘脑和脑干部位脑血流灌注出现明显下降,经电刺激治疗后,患者缺血部位脑血流明显改善,且额叶底面、海马回等区域也出现血流灌注增加表现.结论 颅脑创伤昏迷状况下存在脑血流灌注低下区域,右正中神经电刺激术不仅可显著改善颅脑创伤昏迷患者皮层及丘脑和脑干血流灌注状况,而且可以增加额叶、颞叶底面皮质的血流灌注,提示右正中神经电刺激可能通过改善脑重要功能部位血流状况达到促醒作用.     

Neurobiological consequences of traumatic brain injury

Traumatic brain injury (TBI) is a worldwide public health problem typically caused by contact and inertial forces acting on the brain. Recent attention has also focused on the mechanisms of injury associated with exposure to blast events or explosions. Advances in the understanding of the neuropathophysiology of TBI suggest that these forces initiate an elaborate and complex array of cellular and subcellular events related to alterations in Ca(++) homeostasis and signaling. Furthermore, there is a fairly predictable profile of brain regions that are impacted by neurotrauma and the related events. This profile of brain damage accurately predicts the acute and chronic sequelae that TBI survivors suffer from, although there is enough variation to suggest that individual differences such as genetic polymorphisms and factors governing resiliency play a role in modulating outcome. This paper reviews our current understanding of the neuropathophysiology of TBI and how this relates to the common clinical presentation of neurobehavioral difficulties seen after an injury.     

Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury

The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 si RNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.     

正中神经电刺激对创伤性颅脑损伤昏迷促醒作用的Meta分析

目的系统评价正中神经电刺激（MNS）对创伤性颅脑损伤（TBI）昏迷促醒作用。 方法全面检索Pubmed、Web of Science、Embase、The Cochrane Library、中国知网、中国生物医学文献数据库、万方数据库及维普数据库收录的关于MNS治疗与常规昏迷促醒疗法治疗TBI昏迷患者的随机对照试验,检索时间均自建库至2022年3月。由2名研究者按照纳入与排除标准进行文献筛选、数据提取和质量评价。按照干预措施的不同,将患者分为常规治疗组和MNS组,常规治疗组采用常规治疗方法,MNS组在常规治疗方法的基础上采用MNS治疗。采用Stata12.0软件进行Meta分析的合并效应量计算、异质性检验和发表偏倚检验。 结果本研究纳入21篇文献,共计1684例患者。Meta分析结果显示,治疗1、2、3、4周后,与常规治疗相比,MNS可以提高患者GCS评分（P<0.001）,且苏醒率更高（OR=2.13,95%CI：1.56~2.91）。MNS组的脑功能障碍评分（SMD=-0.66,95%CI：-0.96~-0.36）低于常规治疗组,运动能评分（SMD=0.25,95%CI：0.00~0.50）、生活质量评分（SMD=0.85,95%CI：0.53~1.18）、EEG评分（SMD=1.04,95%CI：0.23~1.86）均高于常规治疗组。 结论MNS能够改善4周内TBI昏迷患者意识水平,具有促进清醒的作用。     

A novel therapeutic target for peripheral nerve injury-related diseases: aminoacyl-tRNA synthetases

Aminoacyl-t RNA synthetases(Amino ARSs) are essential enzymes that perform the first step of protein synthesis. Beyond their original roles, Amino ARSs possess non-canonical functions, such as cell cycle regulation and signal transduction. Therefore, Amino ARSs represent a powerful pharmaceutical target if their non-canonical functions can be controlled. Using Amino ARSs-specific primers, we screened m RNA expression in the spinal cord dorsal horn of rats with peripheral nerve injury created by sciatic nerve axotomy. Of 20 Amino ARSs, we found that phenylalanyl-t RNA synthetase beta chain(FARSB), isoleucyl-t RNA synthetase(IARS) and methionyl-t RNA synthetase(MARS) m RNA expression was increased in spinal dorsal horn neurons on the injured side, but not in glial cells. These findings suggest the possibility that FARSB, IARS and MARS, as a neurotransmitter, may transfer abnormal sensory signals after peripheral nerve damage and become a new target for drug treatment.     

Exogenous nerve growth factor protects the hypoglossal nerve against crush injury

Studies have shown that sensory nerve damage can activate the p38 mitogen-activated protein kinase(MAPK)pathway,but whether the same type of nerve injury after exercise activates the p38MAPK pathway remains unclear.Several studies have demonstrated that nerve growth factor may play a role in the repair process after peripheral nerve injury,but there has been little research focusing on the hypoglossal nerve injury and repair.In this study,we designed and established rat models of hypoglossal nerve crush injury and gave intraperitoneal injections of exogenous nerve growth factor to rats for 14 days.p38MAPK activity in the damaged neurons was increased following hypoglossal nerve crush injury;exogenous nerve growth factor inhibited this increase in acitivity and increased the survival rate of motor neurons within the hypoglossal nucleus.Under transmission electron microscopy,we found that the injection of nerve growth factor contributed to the restoration of the morphology of hypoglossal nerve after crush injury.Our experimental findings indicate that exogenous nerve growth factor can protect damaged neurons and promote hypoglossal nerve regeneration following hypoglossal nerve crush injury.     

Phrenic nerve transfer to the musculocutaneous nerve for the repair of brachial plexus injury: electrophysiological characteristics

Phrenic nerve transfer is a major dynamic treatment used to repair brachial plexus root avulsion. We analyzed 72 relevant articles on phrenic nerve transfer to repair injured brachial plexus that were indexed by Science Citation Index. The keywords searched were brachial plexus injury, phrenic nerve, repair, surgery, protection, nerve transfer, and nerve graft. In addition, we performed neurophysiological analysis of the preoperative condition and prognosis of 10 patients undergoing ipsilateral phrenic nerve transfer to the musculocutaneous nerve in our hospital from 2008 to 201 3 and observed the electromyograms of the biceps brachii and motor conduction function of the musculocutaneous nerve. Clinically, approximately 28% of patients had brachial plexus injury combined with phrenic nerve injury, and injured phrenic nerve cannot be used as a nerve graft. After phrenic nerve transfer to the musculocutaneous nerve, the regenerated potentials first appeared at 3 months. Recovery of motor unit action potential occurred 6 months later and became more apparent at 12 months. The percent of patients recovering ‘excellent' and ‘good' muscle strength in the biceps brachii was 80% after 18 months. At 12 months after surgery, motor nerve conduction potential appeared in the musculocutaneous nerve in seven cases. These data suggest that preoperative evaluation of phrenic nerve function may help identify the most appropriate nerve graft in patients with an injured brachial plexus. The functional recovery of a transplanted nerve can be dynamically observed after the surgery.     

Clinical translation of stem cell therapy in traumatic brain injury: the potential of encapsulated mesenchymal cell biodelivery of glucagon-like peptide-1

Traumatic brain injury remains a major cause of death and disability; it is estimated that annually 10 million people are affected. Preclinical studies have shown the potential therapeutic value of stem cell therapies. Neuroprotective as well as regenerative properties of stem cells have been suggested to be the mechanism of action in preclinical studies. However, up to now stem cell therapy has not been studied extensively in clinical trials. This article summarizes the current experimental evidence and points out hurdles for clinical application. Focusing on a cell therapy in the acute stage of head injury, the potential of encapsulated cell biodelivery as a novel cell-therapeutic approach will also be discussed.