Vimentin as a potential target for diverse nervous system diseases

Vimentin is a major type Ⅲ intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protein, it also exists in the extracellular matrix and at the cell surface. Previous studies have shown that vimentin may exert multiple physiological effects in different nervous system injuries and diseases. For example, the studies of vimentin in spinal cord injury and stroke mainly focus on the formation of reactive astrocytes. Reduced glial scar, increased axonal regeneration, and improved motor function have been noted after spinal cord injury in vimentin and glial fibrillary acidic protein knockout(GFAPVIM) mice. However, attenuated glial scar formation in post-stroke in GFAP–/– VIM–/– mice resulted in abnormal neuronal network restoration and worse neurological recovery. These opposite results have been attributed to the multiple roles of glial scar in different temporal and spatial conditions. In addition, extracellular vimentin may be a neurotrophic factor that promotes axonal extension by interaction with the insulin-like growth factor 1 receptor. In the pathogenesis of bacterial meningitis, cell surface vimentin is a meningitis facilitator, acting as a receptor of multiple pathogenic bacteria, including E. coli K1, Listeria monocytogenes, and group B streptococcus. Compared with wild type mice, VIMmice are less susceptible to bacterial infection and exhibit a reduced inflammatory response, suggesting that vimentin is necessary to induce the pathogenesis of meningitis. Recently published literature showed that vimentin serves as a double-edged sword in the nervous system, regulating axonal regrowth, myelination, apoptosis, and neuroinflammation. This review aims to provide an overview of vimentin in spinal cord injury, stroke, bacterial meningitis, gliomas, and peripheral nerve injury and to discuss the potential therapeutic methods involving vimentin manipulation in improving axonal regeneration, alleviating infection, inhibiting brain tumor progression, and enhancing nerve myelination.

Ameliorative effects of standardized extract from Trigonella foenum-graecum L.seeds on painful peripheral neuropathy in rats

Objective:To evaluate the effects of the standardized extract of fenugreek(Trigonella foenumgraecum L.Family:Leguminasae) seed(IND01) in animal models of peripheral neuropathy. Methods:IND01 was prepared from fenugreek seeds and standardized by high performance liquid chromatography to a marker compound,trigonelline.The effects of daily oral administration of IND01(50,100 and 200 mg/kg) were studied in rats after partial sciatic nerve ligation(PSNL) and sciatic nerve crush injury(SNCI) during 30-days period.The measurements on thermal hyperalgesia(TH),motor function test(MFT) score and motor nerve conduction velocity (MNCV) were recorded.Results:IND01 offered sustained protection against TH and deranged MFT scores in both models from 7-day onwards.Fifteen days of daily oral administration of IND01 restored MNCV reduction in rats with SNCI but not with PSNL.Conclusions:IND01 was found to be effective in rat models of painful peripheral neuropathy.

Glymphatic system:a gateway for neuroinflammation

The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the brain.Accumulating evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic diseases.Systemic diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous system.This review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system inflammation.In addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and neurodegeneration.Future research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.

Traditional Chinese Medicine syndrome analysis on oxaliplatin-induced peripheral neuropathy and clinical efficacy of Bushen Yiqi formula(补肾益气方):a prospective randomized controlled study

OBJECTIVES:To analyze the distribution characteristics of Traditional Chinese Medicine(TCM)syndromes in patients with oxaliplatin-induced peripheral neuropathy(OIPN)and observe the clinical efficacy of Bushen Yiqi formula(补肾益气方,BSYQF)in treating patients with OIPN.METHODS:A total of 89 patients with OIPN were enrolled in this study.The TCM syndrome characteristics were investigated by frequency analysis methodology after collecting and analyzing the TCM syndrome elements of the patients with the OIPN TCM syndrome element scale.Further,62 cases of cold-dampness obstruction syndrome and kidney-Qi deficiency and cold syndrome were selected and randomly divided into the control group(n=31)and the treatment group(n=31).The patients in the treatment group were treated with modified BSYQF,while those in the control group were treated with mecobalamin tablets for 3 weeks.The Levi sensory neurotoxicity score and the neuro-electrophysiological changes were observed before and after the treatment in both groups.RESULTS:The distribution of TCM syndrome types in 89 patients with OIPN were in order of kidney-Qi deficiency and cold syndrome(44 cases),cold-dampness obstruction syndrome(18 cases),Yin deficiency of liver and kidney syndrome(11 cases),blood stasis obstruction syndrome(7 cases),and dampness-heat obstruction syndrome(5 cases).Improvement in Levi sensory neurotoxicity score:After 3-week treatment,the total effective rate in the treatment group was higher than that in the control group(P<0.05).The subgroup analysis showed that the total effective rate in the treatment group of patients with kidney-Qi deficiency and cold syndrome was higher than that in the control group before and after treatment(P<0.05).Improvement in nerve conduction velocity:The sensory nerve conduction velocity of bilateral ulnar nerves improved in the control group after treatment compared with that before treatment(P<0.05).The sensory and motor nerve conduction velocities of the bilateral ulnar and bilateral peroneal nerves improved in the treatment group compared with those before treatment and after treatment in the control group(P<0.05).CONCLUSIONS:The modified BSYQF had a definite therapeutic effect on the OIPN in patients with kidney-Qi deficiency and cold syndrome and those with cold-dampness obstruction syndrome.It could effectively reduce the grade of peripheral nerve toxicity and improve nerve conduction velocity,and its curative effect was better than that of mecobalamin tablets.

Morphological changes in interstitial cells of Cajal in the deep muscular plexus and enteric motor neurons of the intestine in rats with multiple organ dysfunction syndrome

BACKGROUND：Gastrointestinal motility dysfunction in multiple organ dysfunction syndrome （MODS） has been reported to be related to damage to interstitial cells of Cajal （ICC）. In the entedc nervous system, ICC and smooth muscle cells are connected in a network to form a special functional unit. Many gastrointestinal motility dysfunction diseases are associated with damage to this network.OBJECTIVE：To investigate the morphological changes of intestinal ICC, and to explore the mechanisms underlying gastrointestinal motility dysfunction in rats with MODS.DESIGN, TIME AND SE＇I-FING：The randomized, controlled, experiment was performed at the Central Laboratory of the First Affiliated Hospital of Dalian Medical University of China between June 2007 and March 2009.MATERIALS：Escherichia coli （E. colistrain O127 H6） and bovine serum albumin were purchased from Sigma, USA.METHODS：A total of 40 Wistar rats were equally and randomly divided into MODS group and control group. Suspension of E. coil strain O127 H6 containing BaSO4 and saline were sterilely injected into the abdominal cavity of rats in the MODS and control groups, respectively.MAIN OUTCOME MEASURES：Immunohistochemical double-staining and confocal laser scanning microscopy were used to observe the morphological changes in intestinal cholinergic nerves and ICC in the deep muscular plexus network. Electron microscopy was employed to evaluate the ultrastructural features of ICC in the deep muscular plexus of rats with MODS.RESULTS：Compared with the control group, the distributions and densities of cholinergic/nitrergic newes and ICC in the deep muscular plexus were significantly decreased in the MODS group （P 〈 0.01）. The enteric nerve-ICC network were disrupted.CONCLUSION：There is ultrastructural injury in the ICC in the deep muscular plexus and enteric nerves of the intestine in rats with MODS, which may be associated with the dysmotility of the gastrointestinal tract in MODS.

Mononeuropathy multiplex associated with systemic vasculitis:A case report

BACKGROUND Vasculitis,a systemic disorder with inflammation of blood vessel walls,can develop broad spectrum of signs and symptoms according to involvement of various organs,and therefore,early diagnosis of vasculitis is challenging.We herein describe a patient who developed a special case of systemic vasculitis with mononeuropathy multiplex,rectal perforation and antiphospholipid syndrome(APS)presented with pulmonary embolism.CASE SUMMARY A 61-year-old woman visited hospital with complaints of myalgia and occasional fever.She was initially diagnosed as proctitis and treated with antibiotics,however,there was no improvement.In addition,she also complained right foot drop with hypesthesia,and left 2^(nd) and 3^(rd) finger tingling sensation.She underwent nerve conduction study for evaluation,and it revealed sensorimotor polyneuropathy in the left arm and bilateral legs.Subsequent sural nerve biopsy strongly suggested vasculitic neuropathy.Based on nerve biopsy and clinical manifestation,she was diagnosed with vasculitis and treated with immunosuppressive therapy.During treatment,sudden rectal perforation and pulmonary thromboembolism occurred,and further laboratory study suggested probable concomitant APS.Emergency Hartmann operation was performed for rectal perforation,and anti-coagulation therapy was started for APS.After few cycles of immunosuppressive therapy,tingling sensation and weakness in her hand and foot had been partially recovered and vasculitis was considered to be stationary.CONCLUSION Vasculitis can be presented with a variety of signs and symptoms,therefore,clinicians should always consider the possibility of diagnosis.

神经生长因子治疗酒精中毒性周围神经病患者的疗效观察

[目的]探讨神经生长因子治疗酒精性周围神经病（CAPN）患者的临床疗效.[方法]将CAPN患者56例分为两组：治疗组32例,肌注神经生长因子4 mL（1000 u）,每日1次;对照组24例,给予肌注维生素B1 0.1 g,每日1次,每组均给予丹参静脉点滴及理疗辅助治疗.两组患者治疗前后均采用丹麦丹迪公司CantataTM型肌电图仪测定,比较两组患者症状、体征及正中神经、腓总神经的运动神经传导速度（MNCV）和感觉神经传导速度（SNCV）.[结果]患者四肢末端疼痛、麻木、蚁走感、走路不稳症状和腱反射、浅感觉治疗组治疗后与治疗前比较有显著性差异（P〈0.05）,对照组治疗前与治疗后及与治疗组治疗前比较均无显著性差异（P〉0.05）;治疗组治疗后MNCV和SNCV显著高于治疗前（P〈0.05）,对照组治疗前与治疗后及与治疗组治疗前比较均无显著性差异（P〉0.05）.[结论]神经生长因子治疗酒精中毒性周围神经病患者疗效满意,值得临床推广应用.

Value of sympathetic skin response test in the early diagnosis of diabetic neuropathy

Background Diabetic neuropathy is common in diabetes mellitus. The early stage of diabetic neuropathy is often symptomless and difficult to be treated. The aim of this study was to assess the correlation between the results of the sympathetic skin response (SSR) test and the development of diabetic neuropathy, and explore the use of SSR as an objective basis for the early diagnosis of diabetic neuropathy. Methods The latencies and amplitudes of initiation and of the N and P waves were determined by SSR testing of the extremities of 80 diabetic patients and 30 healthy controls. Results The latencies of initiation and of the N and P waves were significantly (P<0.001) longer in diabetic patients than in the controls, while there was no significant difference in the amplitudes (P>0.05). All but two patients (97.5%) demonstrated abnormal SSR in at least one limb. Conclusions SSR can detect early dysfunction of the small sympathetic fibers in people affected by diabetes mellitus, and may be a useful electrophysiological test for the early diagnosis of diabetic neuropathy.