Effect of exogenous trivalent iron ions on tau phosphorylation and aggregation in SH-SY5Y cells / 环境与职业医学

Background A large amount of iron deposition in the brain can cause neuronal damage by inducing oxidative stress, neuroinflammation, and abnormal mitochondrial function. In addition, iron deposition is also reported to be closely related to the pathogenesis of Alzheimer's disease (AD). The neurofibrillary tangles aggregated by tau hyperphosphorylation are one of the important pathological features of AD. Objective To investigate potential effect of exogenous trivalent iron ions on neuronal activity in human neuroblastoma (SH-SY5Y) cells and tau hyperphosphorylation and aggregation. Methods SH-SY5Y cells were treated with ferric chloride (FeCl3) at four concentrations (10, 100, 200, and 400 mg·L−1). Cell survival rate was then detected by CCK8 assay. Intracellular iron content was determined prussian blue (Perl's) by iron staining after 24 h exposure to FeCl3 at 10 or 200 mg·L−1. Transfection of tau-P301L plasmid was conducted to construct an AD-like cell model for tau overexpression. The differences in the expression of the phosphorylated tau (p-tau) protein in SH-SY5Y cells and SH-SY5Y cells with tau overexpression were detected by Western blotting after 24 h exposure to FeCl3 at 10 and 200 mg·L−1. After dilution with phosphate buffered saline (PBS), FeCl3, human tauR3, and FeCl3 + tauR3 were incubated at 37℃, and the fluorescence intensity reflecting tau aggregation level was measured by thioflavin T(ThT) method at 12, 24, 36, 48, 60, 72, 84, and 96 h, respectively. Meanwhile, after 96 h coincubation of FeCl3 and tauR3, the fibers formed by tau aggregation were observed under a transmission electron microscope (TEM). Results After 24 h of FeCl3 exposure, the cell survival rate of SH-SY5Y cells among all groups was statistically different (F=8.63, P<0.01). The cell survival rates in the 200 and 400 mg·L−1 groups were 80.1% and 68.7% of the control group, respectively (P<0.05). Compared with the control group, the nuclei of the 200 mg·L−1 FeCl3 group were mainly yellowish-brown after iron staining and the positive cell rate was up-regulated by 12.9% (P<0.01). After 24 h of FeCl3 exposure , the p-tau (Ser396) protein expression was statistically different among all groups (F=11.6, P<0.01). Compared with the control group, the p-tau protein expression level of SH-SY5Y cells in the 200 mg·L−1 group was up-regulated by 72.7% (P<0.01). After FeCl3-treated SH-SY5Y cells with tau overexpression for 24 h, the p-tau (Ser396) protein expression was statistically different among all groups (F=27.8, P<0.01). Compared with the tau group, the p-tau (Ser396) protein expression level of SH-SY5Y cells in the tau + 200 mg·L−1 group was up-regulated by 44.6% (P<0.05). Compared with the tauR3 group, the fluorescence intensities in the 84 and 96 h tauR3 + FeCl3 groups were up-regulated by 49.9% and 53.7% (P<0.01) respectively. After 96 h of coincubation, compared with the tauR3 group, FeCl3 + tauR3 aggravated tau aggregation and formed fiber deposition under TEM. Conclusion Exogenous trivalent iron ions may inhibit SH-SY5Y cell viability, promote the phosphorylation of tau in SH-SY5Y cells transfected with tau-P301L plasmid, and aggravate tauR3 aggregation and fiber production.

Guillain-Barré syndrome / 中华神经科杂志

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots, which is usually triggered by infections. It is characterized by rapidly progressive, symmetrical weakness of the extremities. Some patients develop respiratory insufficiency and many show signs of autonomic dysfunction. Diagnosis can usually be made on clinical grounds, but lumbar puncture and electrophysiological studies can help to substantiate the diagnosis and to differentiate demyelinating from axonal subtypes of GBS. Molecular mimicry of pathogen-borne antigens, leading to generation of crossreactive antibodies that also target gangliosides, is generally accepted pathogenesis of GBS. The treatment of GBS is intravenous immunoglobulin or plasma exchange with general clinical treatment. Most patients have a good prognosis and basically recover within weeks to months. A few patients have persistent neurological dysfunction or even death.

Vigabatrin-associated brain abnormalities on magnetic resonance imaging in the treatment of infantile spasms: a case report / 中华神经科杂志

Vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM) is a relatively rare side effect of vigabatrin, most of which are asymptomatic. However, there will be extremely rare cases with hyperkinetic disorders, myoclonus, tremor, and acute encephalopathy under certain circumstances. VABAM is often underappreciated by physicians and its accurate incidence remains unclear. A female infant who was diagnosed with infantile spasms and required adrenocorticotropic hormone therapy accompanied by various antiseizure medicines was reported. Unfortunately, she became lethargic and her spasm deteriorated gradually after vigabatrin exposure. Her brain magnetic resonance imaging revealed abnormal signals bilaterally in the dorsal midbrain, thalamus, and rostral part of the pallidum. She had a seizure amelioration and became lively as a result of vigabatrin withdrawal. In the meanwhile, magnetic resonance imaging returned to normal. Attempts were made to discover the risk factors of VABAM and potential pathogenesis. Further understanding of the disease should contribute to decreasing misdiagnosis and making precise decisions.

Optic neuritis in Guillain-Barré syndrome: a case report and literature review / 中华神经科杂志

Objective:To summarize the clinical characteristics of patients with Guillain-Barré syndrome (GBS) complicated with optic neuritis (ON).Methods:The clinical data of a patient with GBS complicated with ON, who admitted to the Department of Neurology, the First Hospital of Shanxi Medical University in December 2021, were collected, including demographic characteristics, clinical symptoms and signs, laboratory and electrophysiological data, and results of fundus color films. The patients with GBS complicated with ON reported in the literature were also reviewed.Results:A 40-year-old female patient with GBS was diagnosed by the results of electromyography and cerebrospinal fluid tests combining with the history and signs, who was treated with intravenous immunoglobulin on the 3rd day after onset. On the 8th day, her muscle strength improved significantly. However, on the 12th day, the visual field darkened, and on the 19th day, the vision decreased significantly (oculus dexter visual acuity 0.2, oculus sinister visual acuity 0.1 +1) with bilateral papilloedema, a relative afferent pupillary defect and delayed P100 response of the visual evoked potential. Obvious abnormality was not noted in optic nerve magnetic resonance imaging. Thus ON was diagnosed and treated with pulse methylprednisolone therapy. After 8 days of treatment, the visual acuity was completely recovered and there was no abnormality in the ocular fundus. A total of 28 cases of GBS complicated with ON (including the present patient) were reported in the literature. The age of onset was mostly 20-60 years, and there was no gender preference. Mycoplasma pneumoniae was the most common premorbid pathogen and was identified in 7 of the 10 cases in which the causative agent was described. ON usually involved both sides, and 21 of 28 patients had bilateral optic nerves involved. GBS preceded ON or both occurred simultaneously in the majority of patients; GBS preceded ON in 14 of 28 patients, and both occurred simultaneously in 10 of 28 patients. All patients responded well to immunotherapy, and vision was completely recovered in 20 patients. Conclusions:GBS complicated with ON is rare. Attention should be paid to the loss of vision in patients with GBS. Relevant examinations should be completed as soon as possible and immunotherapy should be given.

Anti-neurofascin 186 antibody associated acute immune sensory polyradiculopathy: a case report and review of literature / 中华神经科杂志

Objective:To describe the clinical features of a patient of anti-neurofascin 186 (NF186) antibody associated acute immune sensory polyradiculopathy (AISP), and enhance understanding of AISP/chronic immune sensory polyradiculopathy (CISP).Methods:The clinical characteristics, diagnosis and treatment of a domestic AISP patient with NF186 antibody positive admitted to the First Hospital of Shanxi Medical University in December 2021 were summarized, and the previously reported cases of AISP/CISP were systematically reviewed.Results:The patient was a 62-year-old male with acute onset. The clinical manifestations included severe sensory ataxia, increased protein in cerebrospinal fluid, no response to stimulation of the central segment of somatosensory evoked potentials (SEP), normal sensory and motor nerve conduction, and positive serum anti-NF186 antibody (1∶32). After glucocorticoid treatment, the clinical symptoms and SEP were significantly improved. The drug was stopped for 2 months, and there was no recurrence. There were 23 cases of AISP and CISP with complete data reported in the literature (including this patient). The age of onset was (54.7±17.7) years, and the ratio of male to female was 1.88. Three patients with acute onset were classified as AISP. A total of 95.7% (22/23) of patients showed sensory ataxia without limb weakness, 95.0% (19/20) of patients showed prolonged cortical potential latency or even no response, and 95.5% (21/22) of patients showed increased cerebrospinal fluid protein in varying degrees, and nerve root thickening or abnormal enhancement was not common. All 10 patients receiving immunotherapy responded to corticosteroids or intravenous immune globulin. Only 6 AISP/CISP articles reported screening for anti-ganglioside antibodies or Ranvier′s node-paranodal region-related antibodies, and no positive NF186 antibodies were reported. All the 3 patients with AISP had some characteristics of CISP/chronic inflammatory demyelinating polyradiculoneuropathy, and there was no significant difference between AISP and CISP patients in clinical features except the mode of onset.Conclusions:NF186 antibody could cause AISP, which presents as acute onset sensory ataxia. AISP is responsive to glucocorticoid therapy. Except for the mode of onset, AISP and CISP are difficult to distinguish from clinical, electrophysiological, pathological aspects and pathogenic antibodies, so they may be two different manifestations of the same disease.

Rational application of gene testing in the diagnosis of myopathy / 中华神经科杂志

With the development and popularity of genetic testing, more and more clinicians are over-relying on genetic testing for the diagnosis of hereditary myopathy, a rare disease, leading to misdiagnosis for patients and causing a huge economic burden to the society and family. It is essential for clinicians to further understand the limitations of gene testing and attach more attention to the clinical characteristics, which might be suggestive for the clinical diagnosis of hereditary myopathy. During the process of accurate diagnosis, gene testing should be selected based on the clinical manifestations, promoting its rational application in the diagnosis of hereditary myopathy.

Biofluid Biomarkers of Alzheimer's Disease: Progress, Problems, and Perspectives / 神经科学通报·英文版

Since the establishment of the biomarker-based A-T-N (Amyloid/Tau/Neurodegeneration) framework in Alzheimer's disease (AD), the diagnosis of AD has become more precise, and cerebrospinal fluid tests and positron emission tomography examinations based on this framework have become widely accepted. However, the A-T-N framework does not encompass the whole spectrum of AD pathologies, and problems with invasiveness and high cost limit the application of the above diagnostic methods aimed at the central nervous system. Therefore, we suggest the addition of an "X" to the A-T-N framework and a focus on peripheral biomarkers in the diagnosis of AD. In this review, we retrospectively describe the recent progress in biomarkers based on the A-T-N-X framework, analyze the problems, and present our perspectives on the diagnosis of AD.

Pay attention to COVID-19 with peripheral neuropathy / 中华神经科杂志

Although the outbreak of COVID-19 has been under control in China, the outbreak and epidemic of the disease are still increasing worldwide, and the number of deaths is still increasing. The COVID-19 cases are indeed dominated by varying degrees of lung damage, which is also the leading cause of death. However, professionals of various clinical disciplines are paying attention to whether there are important damages to other systems. Colleagues in neurology are more concerned about whether COVID-19 directly or indirectly affects the neurologic system. Judging from more than 80 000 cases in China, there are few objective evidences that the neurologic system is actually damaged in the reported data. Since the pandemic in Europe and America, some cases of combined peripheral nerve involvement have been reported, which deserves the attention of colleagues.

Paramyotonia congenita and hypokalemic periodic paralysis in a family with mutation p.R1448H in α-subunit type Ⅳ of voltage gated sodium channel gene / 中华神经科杂志

Objective Through description of the clinical,electrophysiological,pathological and gene sequencing characteristics of a family diagnosed as paramyotonia congenita and hypokalemic periodic paralysis to broaden the understanding of skeletal muscle channel disease and provide the reference for clinical diagnosis.Methods The clinical manifestation,electromyography,muscle pathology and gene sequencing of a family diagnosed as paramyotonia congenita and hypokalemic periodic paralysis in the First Hospital of Shanxi Medical University in October 2017 were collected.Results The proband represented myotonia and episodic muscle weakness,and the manifestations of different patients of the family were varied,including myotonia,episodic muscle weakness or myotonia and episodic muscle weakness.The electromyography of the proband showed myotonic potential,and the compound muscle action potential decreased by 36％ in 40 minutes after exercise in the long exercise test in cold environment (11 ℃).The gene sequencing showed α-subunit type Ⅳ of voltage gated sodium channel (SCN4A) gene p.R1448H mutation.Conclusions The proband presented with paramyotonia congenita and hypokalemic periodic paralysis.Family clinical manifestations suggested phenotypic heterogeneity.The long exercise text in cold environment (11 ℃) confirmed the diagnosis of the proband as paramyotonia congenita and hypokalemic periodic paralysis.Family gene sequencing showed that the mutation of p.R1448H in SCN4A gene was the pathogenic gene mutation site of paramyotonia congenita and hypokalemic periodic paralysis.

A family with Andersen-Tawil syndrome induced by a new mutation Q164R in the KCNJ2 gene and previous literature review / 中华神经科杂志

Objective To discuss clinical characteristics of a family with Andersen-Tawil syndrome, test and analyze the mutation of their pathogenic gene, and to discover the dependency of genotype and phenotype by searching every reported Andersen-Tawil syndrome patient in all accessible literature worldwide.Methods In December 2nd,2016,two patients in the Department of Neurology,the First Hospital of Shanxi Medical University, received medical history data collection and relevant examinations.PCR and DNA sequencing were applied to detect ion channel diseases related genes such as SCN4A, CACNA1S, KCNJ2, KCNE3, KCNE4, KCNJ18, KCNJ5.Random selection of 200 healthy volunteers from Shanxi Medical University served as normal controls.Andersen-Tawil syndrome cases,which are accorded with statistical criteria in published literature, were collected.Their genotype and phenotype were analyzed and summarized.Results Clinical manifestation of the pre-confirmed patient and his father was accorded with diagnostic criteria of Andersen-Tawil syndrome.Prominent characteristics included ventricular arrhythmia, periodic paralysis, and dysmorphic features.The two patients had renal tubular acidosis.One of these two patients also had increased level of renin-angiotensin-aldosterone.New mutation Q164R in the KCNJ2 gene was found in these two patients.There was no report in any literature or any database that we could find about this gene mutation at present.The mutation was not found among other healthy family members and 200 healthy controls.In this study,we referenced 55 samples of Andersen-Tawil syndrome in 12 articles,in which 54 samples are KCNJ2 gene mutation,one is KCNJ5 gene mutation.We concluded a negative correlation between the onset age of periodic paralysis and the onset age of cardiac symptoms after a statistical analysis of these 54 patients with KCNJ2 gene mutation(rs=-0.698 1,P=0.005 5).The incidence of cardiac symptoms in patients of Andersen-Tawil syndrome with periodic paralysis was reduced(33.33%(14/42)vs 9/11, χ2=6.485,P=0.011).Men(96.00%(24/25))were found more likely to have periodic paralysis than women(65.52%(19/29); χ2=7.691,P=0.006).Women (64.29%(18/28))were found more likely to have cardiac symptoms than men(20.00%(5/25); χ2=10.545,P=0.001).Conclusions New mutation Q164R in the KCNJ2 gene is the cause of Andersen-Tawil syndrome,which could cause renal tubular acidosis.We speculate that the gene may play a role in the way of potassium regulating aldosterone.For women with the KCNJ2 gene mutation and the late-onset of periodic paralysis,it is important to take drug or manual intervention as early as possible to prevent the occurrence of cardiogenic adverse events.

Effects of recombinant human erythropoietin on expressions of tumor necrosis factor-alpha and inter ieukin-6 in rats with acute cerebral ischemia / 中华老年医学杂志

Objective To investigate the effects of recombinant human erythropoietin(rhEPO)on expressions of tumon necrosis factor-alpha(TNF-α) and inter leukin-6(IL-6) in rats after focal cerebral ischemia and to explore its neuroprotective mechanism.Methods A total of 36 healthy male SD rats were randomly divided into sham-operated group (n=12),model group (n=12) and rhEPO treatment group (n=12).The suture method to make permanent middle cerebral artery occlusion model was adopted.rhEPO treatment group was injected with rhEPO 5000 U/kg intraperitoneally after 2 h of ischemia,whereas model group and sham-operated group were given identical saline at the same time.All rats were decapitated after 24 h of ischemia.6 rats were randomly selected in each group and the infarct volume of groups were measured by Triphenyl tetrazolium chloride (TTC)staining method.The expressions of TNF-α,IL-6 in other rats were detected by immunohistochemistry.Results No infarction was found in sham-operated group.Percentage of infarct volume in model group and rhEPO group were (36.672.40)％ and (27.49± 1.47)％,respectively.Compared with the model group,the volume of infarction in rhEPO group was significantly reduced.Cells stained by immunohistochemistry showed that The numbers of TNF-α-positive cells in the 3 groups were 9.001.41,27.83±2.48,17.50±1.87 and IL 6 positive cells were 8.94±2.31,20.33±3.53,14.83±1.70,respectively.Compared with sham operated group,the expressions of TNF-α and IL 6 in model group were significantly increased (q=16.1,19.6,P＜0.01).Compared with the model group,the expressions of TNF α and IL-6 in rhEPO group were significantly decreased (q=8.19,3.44,all P＜0.01).Conclusions rhEPO can decrease the infarct volume in SD rats after acute focal cerebral ischemic injure.rhEPO might exert its neuroprotective effect by reducing the expressions of TNF α and IL-6.

Reversible Posterior Leukoencephalopathy Syndrome during Gestation Period: 4 Cases Report / 中国康复理论与实践

@#ObjectiveTo explore the clinical and imageological features of reversible posterior leukoencephalopathy syndrome(RPLS) during gestation period.MethodsClinical and imageological data of 4 pregnant women with RPLS were analyzed retrospectively.ResultsHeadache, seizure, confusion and visual loss were the mainly clinical manifestations. At MR imaging, the brain typically demonstrated focal regions of symmetric hemispheric edema which may disappear in several weeks. The parietal and occipital lobes were most commonly affected, followed by the frontal lobe cerebral vasoconstriction syndrome. Three of the four patients suffered eclampsia which happened in two days after delivery.ConclusionThere are distinctively clinical features in posterior leukoencephalopathy syndrome during gestation period. Most of them are invovled in patients with eclampsia.

Reversible Cerebral Vasoconstriction Syndrome: a Case Report / 中国康复理论与实践

@#Reversible cerebral vasoconstriction syndrome (RCVS) usually occurs during normal pregnancy or a few days after delivery. The gold standard of diagnosis is the reversibility of cerebral vascular constriction confirmed by digital subtraction angiography (DSA). In this article, we descried the clinical and imaging features of one RCVS case proved by repeating DSA, and discussed the probably pathophysiological mechanisms.

Expression of RECK Gene in Placentas from Patients with Preeclampsia and Its Correlation with MMP-2 Activation / 华中科技大学学报(医学版)

Objective To investigate the expression of RECK gene in placentas of patients with preeclampsia and its correlation with MMP-2 activation,and explore the possible roles of RECK gene in the placental trophoblast invasion mechanism.Methods RT-PCR and Western blot were used to detect the expression of RECK mRNA and protein respectively in the placental tissues of normal late pregnant women (normal pregnant group,22 cases) and pre-eclamptic patients(22 mild cases and 20 severe cases).Gelatinase zymography was used to determine MMP-2 activation ratio.Results The expression levels of RECK mRNA and protein from placenta tissues in mild,severe pre-eclamptic group were both significantly higher than those in nomal pregnant group.Moreover,the expression levels of RECK mRNA and protein in severe pre-eclamptic group were obviously increased as compared with those in mild pre-eclamptic group.There was significant difference among the three groups (all P<0.01).MMP-2 activation ratio in mild,severe pre-eclamptic group was significantly lower than that in normal pregnant group.MMP-2 activation ratio in severe pre-eclamptie groups was obviously reduced as compared with mild pre-eclamptic group.There was significant difference among the three groups(all P<0.01).The expression leVels of RECK mRNA and protein were significantly negatively correlated with MMP-2 activation ratio (both P<0.01).Conclusion The abnormal high expression of RECK and inhibition of MMP-2 activation in placentas of pre-eclamptic patients may participate in the process of placental trophoblast shallow invasion.

Diabetic Neuropathy: Advance in Pathology and Electrophysiology (review) / 中国康复理论与实践

@#Diabetic neuropathy is the most common neuropathy. Pathology and electrophysiology are important for early diagnosis of diabetic neuropathy. This article would review the newest progress of the pathology and electrophysiology of diabetic neuropathy.

Correlation of RECK with matrix metalloproteinase-2 in regulation of trophoblast invasion of early pregnancy / 华中科技大学学报（医学）（英德文版）

To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene and matrix metalloproteinase-2 (MMP-2) in the regulation of trophoblast invasion of early pregnancy. Immunohistochemistry, Western blot and gelatin zymography were used to detect the RECK protein expression localization, expression level and MMP-2 activation level in the placental tissues harvested from 52 normal pregnant women (27 in the early pregnancy, 25 in the term pregnancy). Immunohistochemistry showed that RECK expression was found both in villous tissues of early pregnancy group and term pregnancy group and was mainly observed in cell membrane and cytoplasm of cytotrophoblasts and syneytiotrophoblasts. RECK expression increased with gestational time. RECK expression of early pregnancy group was significantly lower than that of term pregnancy group (P<0.05). RECK expression was significantly lower in cellular column (CC) with invasion ability. Western blot showed that the RECK protein expression in early pregnancy group was significantly lower than that in term pregnancy (P<0.05). The optical density values of RECK protein expression in early pregnancy group and term pregnancy group were 1.35-0.14 and 2.68+/-0.26, respectively, while MMP-2 activation ratio was contrary to RECK protein expression and decreased with the gestation time (P<0.01). The MMP-2 activation ratios of early pregnancy group and term pregnancy group were 0.46 +/- 0.05 and 0.10+/-0.02, respectively. The expression of the tumor inhibitory gene RECK was positively related with the invasion ability of trophoblasts, while the invasion gene MMP-2 was negatively related with the ability. The interaction between RECK and MMP-2 may play an important role in the regulation of the trophoblast invasion in early pregnancy.

Correlation of RECK with Matrix Metalloproteinase-2 in Regulation of Trophoblast Invasion of Early Pregnancy / 华中科技大学学报（医学）（英德文版）

To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene and matrix metalloproteinase-2 (MMP-2) in the regulation of trophoblast invasion of early pregnancy. Immunohistochemistry, Western blot and gelatin zymography were used to detect the RECK protein expression localization, expression level and MMP-2 activation level in the placental tissues harvested from 52 normal pregnant women (27 in the early pregnancy, 25 in the term pregnancy). Immunohistochemistry showed that RECK expression was found both in villous tissues of early pregnancy group and term pregnancy group and was mainly observed in cell membrane and cytoplasm of cytotrophoblasts and syneytiotrophoblasts. RECK expression increased with gestational time. RECK expression of early pregnancy group was significantly lower than that of term pregnancy group (P＜0.05). RECK expression was significantly lower in cellular column (CC) with invasion ability. Western blot showed that the RECK protein expression in early pregnancy group was significantly lower than that in term pregnancy (P＜0.05). The optical density values of RECK protein expression in early pregnancy group and term pregnancy group were 1.35±0.14 and 2.68±0.26, respectively, while MMP-2 activation ratio was contrary to RECK protein expression and decreased with the gestation time (P＜0.01). The MMP-2 activation ratios of early pregnancy group and term pregnancy group were 0.46±0.05 and 0.10±0.02, respectively. The expression of the tumor inhibitory gene RECK was positively related with the invasion ability of trophoblasts, while the invasion gene MMP-2 was negatively related with the ability. The interaction between RECK and MMP-2may play an important role in the regulation of the trophoblast invasion in early pregnancy.