Effects of in vivo and in vitro administration of neuro-Behcet’s disease IgG

Antibodies directed against membrane antigens of neuronal axonal processes (neuropil) have been recently identified in neuro-Behcet’s disease (NBD) patients. To delineate the potential pathogenic action of these antibodies, pooled sera from seven NBD patients with neuropil antibodies and seven healthy controls were divided into purified IgG and IgG-depleted serum (IgG-DS) fractions and each fraction was administered into lateral ventricles of rats. NBD IgG-injected rats showed reduced locomotor activity in the open field test as compared to NBD IgG-DS, healthy control IgG, healthy control IgG-DS and PBS injected rats (n = 10 for each group). There were no significant differences among treatment groups by means of anxiety-like behaviors (assessed by elevated plus maze test) and learning/memory functions (assessed by passive avoidance test). Administration of NBD IgG on cultured SH-SY5Y neuroblastoma cells induced significantly increased cell death and apoptosis (as measured by nucleosome levels in the supernatants) as compared to other treatment groups. Our results suggest that IgGs isolated from sera of neuropil antibody-positive NBD patients have a neurotoxic action, which is presumably mediated by apoptotic mechanisms. Motor deficits frequently observed in NBD patients might at least partially be caused by the pathogenic action of anti-neuronal IgG.     

Comparative diagnosis interest of NfL and pNfH in CSF and plasma in a context of FTD–ALS spectrum

Journal of Neurology - The ‘Frontotemporal dementia–Amyotrophic lateral sclerosis Spectrum’ (FAS) encompasses different phenotypes, including cognitive disorders (frontotemporal...     

Challenges in the diagnosis and treatment of transsexualism in contemporary China

##正##According to the International Classification of Diseases10th Edition(ICD-10),[1]transsexualism refers to thecondition where an individual desires to live and to beaccepted as someone of the gender which is oppositetheir biological sex.It is usually accompanied withdiscomfort or distress about their anatomic sex.In somecases,individuals with this condition modify their bodyfeatures using laser or plastic surgeries to resemble     

Values of blink reflex and electroneurography in diagnosis of facial paralysis

BACKGROUND: The electrophysiological test was mainly achieved by the reaction of nerve fiber to electrical stimulus, usually expressed by the amplitude and latency. Blink reflex and electroneurography (ENOG) are widely applied in facial paralysis, the amplitude would step down, and the latency would prolong when the facial nerve was injured. OBJECTIVE: To compare the value of blink reflex and ENOG in the diagnosis of facial paralysis (Bell's palsy). DESIGN: A controlled trial. SETTINGS: Affiliated Hospital, Chengdu University of Traditional Chinese Medicine; West China Hospital of Sichuan University; Mianyang Hospital of Traditional Chinese Medicine; Sichuan People's Hospital. PARTICIPANTS: The patients who had finished the tests of blink reflex (n =207) and ENOG (n =205) were selected from the Affiliated Hospital, Chengdu University of Traditional Chinese Medicine; West China Hospital of Sichuan University; Mianyang Hospital of Traditional Chinese Medicine; Sichuan People's Hospital from September 2001 to July 2003. After treatment for 4 weeks, the patients finished tests of blink reflex (n =207) and ENOG (n =205) were randomly divided into primary treatment group (n =68, 69), acupuncture group (n =71, 66) and comprehensive treatment group (n =68, 70), respectively. Approval was obtained from the ethic committee of hospital. METHODS: Patients in the primary treatment group and acupuncture group were treated with western medicine, acupuncture and moxibustion alone respectively, and those in the comprehensive treatment group were treated with acupuncture and moxibustion based on western medicine. The whole period of treatment was 4 weeks. The tests of blink reflex and ENOG were carried out using Japanese light and electricity MEB-2200 electromyogram/induced potential instrument for once before and after treatment respectively. The normal value of the latency period of wave R1 was within 13 ms, and the difference was 1–1.2 ms between the left and right sides. MAIN OUTCOME MEASURES: The latency of wave R1 of blink reflect and the latency and wave amplitude of ENOG on the affected and healthy sides before and after treatment were observed. RESULTS: Totally 207 and 205 patients received tests of blink reflex and ENOG, but 17 and 16 cases respectively did not finish the second measurement, finally 190 and 189 cases were involved in the analysis of results. The latencies of wave R1 on the affected side after treatment were significantly longer than those before treatment (t =–6.253, P < 0.01); The latencies of wave R1 on the normal side were in the normal range before and after treatment; The latencies of wave R1 before treatment on the affected side was significantly longer than that on the normal side (t =–5.896, P < 0.01), but there were no significant differences between the affected and normal sides after treatment (P > 0.05). It was indicated that the latencies of wave R1 on the affected side had restored normally, and the blink reflex was improved obviously after treatment. The latency of ENOG on the affected side before treatment was significantly prolonged as compared with that on the normal side (t =2.247, P < 0.01); After treatment, the difference between the affected and normal side became smaller, but remarkable significance still existed (t =10.810, P < 0.01). In spite of the obvious improvement of affected side before and after treatment, there were still significant differences (t =–8.110, P < 0.05). The wave amplitude on the affected side was decreased after treatment, which was not significantly different from that before treatment (P >0.05). CONCLUSION: After treatment of facial paralysis, blink reflect was greatly improved, there was an obvious hysteresis in the latency of ENOG. Therefore, blink reflect was better than ENOG in the early diagnosis, while ENOG was suitable for evaluating the prognosis. The ENOG examination was better than blink reflex at middle and late period.     

The effect of amyloidosis-β and ageing on proliferation of neuronal progenitor cells in APP-transgenic mouse hippocampus and in culture

Stimulation of endogenous neurogenesis and transplantation of neuronal progenitors (NPs) are considered in therapy of neuronal loss associated with ageing and in neurodegenerative diseases with amyloidosis-beta, for example, Alzheimer's disease and Down syndrome. However, the influence of brain environment altered by ageing and deposits of amyloid-beta on proliferation of endogenous and transplanted NPs and their maturation into neurons is not understood. We studied the effect of ageing and development of amyloidosis-beta on proliferation of NPs (1) in the granular layer of dentate gyrus in the hippocampi of APP-transgenic mice (Tg9291) before and after development of amyloidosis-beta, that is, in mice aged 2-4 months and 9-12 months, respectively, and in age-matched controls; and (2) in culture of NPs isolated from brains of control and Tg9291 mice, aged 3 and 9 months. We found that the number of proliferating NPs was reduced in 9-12-months-old mice, in both control and Tg9291, as compared to 2-4-months-old mice. However, the 9-12-months-old Tg9291 mice with amyloid-beta deposits had significantly more proliferating NPs than the age-matched controls. NPs proliferation in culture did not depend on the age, presence of APP-transgene, and amyloidosis-beta in donors. The results indicate that the local brain environment influences proliferation of NPs, and development of amyloidosis-beta in the neurogenic regions attenuates the age-associated reduction of proliferation of NPs. Identification of the responsible mechanisms may be important for development of a successful therapy of neurodegeneration caused by amyloidosis-beta.     

Alteration of orexin-A and PKCα in the postmortem brain of pure-opioid and multi-drug abusers

Finding changes induced by the drug of abuse is one of the most important approaches to design new drugs for the treatment of substance use disorders (SUD). Postmortem study is the most reliable method for detecting alteration in the brain of SUD patients. Recently, the role of orexinergic system in SUD is in consideration. In the current study, we evaluated the level of orexin-A in the CSF and protein kinase Cα (PKCα) in the brain of pure-opioid (POA) and multi-drug abusers (MDA).A total of 56 POA, 45 MDA, and 13 matched control brains were collected from the legal medicine center, Tehran, Iran. The CSF was gathered from the third ventricle immediately after opening the skull and kept at −80 °C. The medial prefrontal cortex (mPFC), lateral prefrontal cortex (lPFC), orbitofrontal cortex (OFC), nucleus accumbens (NAc), and amygdala were dissected from fresh brain, frozen with liquid nitrogen and kept at −80 °C. The level of orexin-A evaluated in the CSF. Using western blotting, the level of PKCα assessed in the brain.Obtained data revealed that the level of orexin-A increased in POA and MDA compared with the control group (p < 0.05). In addition, the level of PKCα increased in the prefrontal cortex and amygdala of the abusers compared with the control group, although we did not detect changes in the level of PKCα in the NAc.Along with animal studies, the current results showed that the level of orexin increased in the CSF of drug abusers, which might be related to increases in the activation of lateral hypothalamic orexinergic neurons faced with the drug of abuse. Enhancement in the level of PKCα in the drug reward circuits might be adaptational changes induced by orexin and drugs of abuse.     

Expression of c-Fos protein and nitricoxide synthase in neurons of cerebral cortex from fetal rats in hypoxia and protective role of Angelica sinensis

IN T R O D U C T IO N It is im portant to study the effect of hypoxia in uterus on neurons, because nervous system is one of the earliest developm ental sys- tem s in em bryo, w hose neurons are susceptive to hypoxia terribly. c-fos gene belongs to im m e…     

Changes in the Expression of Genes of the Glutamate Transporter and Subunits of the NMDA and AMPA Receptors in the Rat Amygdala in the Lithium–Pilocarpine Model of Epilepsy

The molecular changes in the glutamatergic system of the rat amygdala were studied during the latent phase of the lithium–pilocarpine model of temporal lobe epilepsy in order to identify the potential involvement of these changes in epileptogenesis. The real-time PCR method was used to evaluate the mRNA expression of the NMDA and AMPA receptor subunits, as well as the excitatory amino acid transporter-2 (EAAT2) in the basolateral nucleus of the amygdala 7 days after the seizures caused by administration of pilocarpine. The results of the experiments were as follows: (1) an increase in the expression ratio of the GluN2a/GluN2b NMDA receptor subunits with an unchanged expression level of the GluN1 subunit; (2) increased expression of the GluA2 subunit of AMPA receptors with the invariance of GluA1, and (3) enhanced expression of the EAAT2. According to literature data, the expression of the same genes decreased in the hippocampus in the same model of epilepsy. Neurodegeneration was reported in both brain regions. The opposite changes in the expression of the glutamatergic system genes in the hippocampus and amygdala during the latent period of the lithium–pilocarpine model suggest the occurrence of factors that can both contribute to and hinder epileptogenesis.     

Injury of mitochondria and the expressions of fas and bax mRNA in the hippocampus of epileptic rats of different latency

IN T R O D U C T IO N M itochondria provide cells energy through oxidative phosphorylation by m eans of ATP. Biochem icalevidence indicates that m ost ATP consum ptions in brain are used forthe electric activity ofneurons, so the sufficientenergy supply f…     

A comparative study of psychopathology in Greek adolescents in Germany and in Greece in 1980 and 1998—18 years apart

Abstract.Objective: In the 1980s, we assessed Greek adolescents living in Germany and Greek adolescents living in Greece. Data from this earlier study supported the hypothesis of selective migration with higher psychopathology self-rating scores in Greek adolescents in Greece as compared to Greek adolescents in Germany. The current study uses the same design and instruments so that the comparison of the mental health of populations in the same areas, almost two decades apart, becomes possible.Methods: In 1980, a total of 2631 Greek adolescents were assessed in Munich, Germany or Veria, Greece. In 1998, 2920 Greek adolescents were assessed in Munich, Germany and Veria, Greece. The General Health Questionnaire (GHQ-28) was used to assess mental health status at both times.Results: 1) GHQ-28 scores showed a significant increase from 1980 to 1998 in both locations. 2) While in 1980, Greeks in Veria, Greece had higher psychopathology scores than Greek adolescents in Munich, Germany, this (with the exception of depression) was no longer true for 1998. 3) At both times and both locations adolescent girls scored higher in the GHQ-28 than adolescent boys.Conclusions: While the 1980 data supported the selective migration hypothesis, this was no longer true for the 1998 data. The increase in psychopathology in both locations is alarming and deserves further exploration.     

Do Canada and the United States differ in prevalence of depression and utilization of services?

OBJECTIVE: This study compared the prevalence of depression and the determinants of mental health service use in Canada and the United States. METHODS: The study used data from preliminary analyses of the 2003 Joint Canada/United States Survey of Health, which measured Canadian (N=3,505) and United States (N=5,183) resident ratings of health and health care services. Cross-national comparisons were made for the 12-month prevalence of DSM-IV major depression, 12-month service use for mental health reasons according to the type of professional seen, and determinants of service use. RESULTS: The rates of depression were similar in Canada (8.2%) and the United States (8.7%). However, U.S. respondents without medical insurance were twice as likely as Canadian respondents and U.S. respondents with medical insurance to meet the criteria for depression. Rates of mental health service use did not differ between Canada (10.1%) and the United States (10.6%). In the United States, medical insurance was not a determinant factor of service use. However, U.S. respondents with no medical insurance were more likely than the other two groups to report an unmet need. Also, among those with depression, U.S. respondents with no medical insurance were less likely to use any type of mental health service (36.5%) than U.S. respondents with medical insurance (55.7%) and Canadians (55.7%). Further, a positive correlation between a mental health need and service use was observed in Canada but not for those without medical insurance in the United States. CONCLUSIONS: There was no difference in the prevalence of depression and mental health service use between Canada and the United States. Among those with depression, however, disparities in treatment seeking were found to be associated with medical insurance in the United States. Both Canada and the United States need to improve access to health services for those with mental disorders, and special attention is needed for those without medical insurance in the United States.     

Functional recovery and muscle atrophy in pre-clinical models of peripheral nerve transection and gap-grafting in mice:effects of 4-aminopyridine

We recently demonstrated a repurposing beneficial effect of 4-aminopyridine(4-AP),a potassium channel blocker,on functional recove ry and muscle atrophy after sciatic nerve crush injury in rodents.However,this effect of 4-AP is unknown in nerve transection,gap,and grafting models.To evaluate and compare the functional recovery,nerve morphology,and muscle atrophy,we used a novel stepwise nerve transection with gluing(STG),as well as 7-mm irreparable nerve gap(G-7/0) and 7-mm isografting in 5-mm g...     

Role of APP and Aβ in synaptic physiology

Alzheimer's disease (AD) is the most common cause of dementia in aging populations. Although amyloid plaques are the hallmark of AD, loss of synapses and synaptic dysfunction are closely associated with the duration and severity of cognitive impairment in AD patients. Amyloid precursor protein (APP) and its cleavage products including Aβ have been suggested as homeostatic regulators of synaptic activity. APP manipulation and Aβ application, in vitro and in vivo, affect synapse formation and synaptic transmission. Moreover, synaptic dysfunction and learning deficits precede Aβ plaque deposition, suggesting that synaptic alterations may underlie the initial development of the disease. Because of the pivotal role of APP and Aβ in AD pathogenesis, it is essential to understand how APP and Aβ modulate synaptic function. Here, we review the roles that APP and Aβ play at the synapses, with particular focus on recent findings for the importance of APP in synaptogenesis and synaptic function.     

Outcome of axonal and demyelinating forms of Guillain-Barré syndrome in children

Previous reports have suggested that outcome is worse in the axonal compared with the demyelinating form of Guillain-Barré syndrome (GBS). We performed a retrospective study of 23 children with electrophysiologically confirmed cases of predominant subtypes of GBS to investigate this issue. The patients were classified based on the electrodiagnostic features: Ten (44%) had acute inflammatory demyelinating polyradiculoneuropathy, eight (35%) had acute motor axonal neuropathy, and five (21%) had acute motor-sensory axonal neuropathy. All patients received a standard intravenous immunoglobulin therapy (0.4 g /kg /day for 5 consecutive days). In the acute phase of the disease, patients with the axonal forms of GBS were more disabled than were those with the demyelinating GBS, as measured by GBS scores. Mechanical ventilation was required in five (38%) patients in the axonal group compared with one (10%) patient in the demyelinating group. There was no significant difference at 6 months in GBS scores between demyelinating and axonal forms of GBS. All 20 survivors recovered completely by 12 months. After standard intravenous immunoglobulin therapy, children with axonal forms of GBS recover more slowly than those with the demyelinating form, but outcome at 12 months appears to be equally favorable in two groups.     

Infections and course of disease in mild forms of Guillain-Barré syndrome

OBJECTIVE: Twenty-eight percent of patients with the Guillain-Barré syndrome remain able to walk unaided. Studying patients with the mild form of Guillain-Barré syndrome can further contribute to knowledge of the spectrum of the syndrome and explore whether this subgroup may need treatment with IV immunoglobulin. METHODS: Patients fulfilling the National Institute of Neurologic and Communicative Disorders and Stroke criteria for Guillain--Barré syndrome were included in a nationwide survey over a 2-year period. Clinical characteristics and serum samples were collected prospectively. In addition, a questionnaire was completed concerning the course and outcome of the disease. RESULTS: A total of 139 patients were included. Nineteen of the patients (14%) included were mildly affected, and 120 (86%) were severely affected. Infections with Epstein-Barr virus were found more frequently in mildly affected patients (p = 0.02). Antiganglioside antibodies were less frequently found in the mildly affected patients (p = 0.03). The degree of severity of the disease between mildly and severely affected patients was different on the day of admission (p < 0.01). Thereafter, the groups showed a remarkably similar rate of progression. Thirty-eight percent of mildly affected patients report problems in hand function and an inability to run at 3 and 6 months (all women, p = 0.02). CONCLUSION: The difference in severity of Guillain--Barré syndrome seems to be determined in an early phase of the disease. Preceding infections and antiganglioside antibodies may influence the initial immune attack, determining the severity of the disease. The presence of residual signs in patients with mild disease may advocate the use of early treatment in mildly affected patients.     

An ecological study of temporal trends in ‘deaths of despair’ in England and Wales

Social Psychiatry and Psychiatric Epidemiology - There is growing interest in the concept of ‘deaths of despair’ (DoD)—defined as deaths from three causes: suicide, drug...     

Effects of exercise on neurogenesis in the dentate gyrus and ability of learning and memory after hippocampus lesion in adult rats

Objective To explore the effects of exercise on dentate gyrus (DG) neurogenesis and the ability of learning and memory in hippocampus-lesioned adult rats. Methods Hippocampus lesion was produced by intrahippocampal microinjection of kainic acid (KA). Bromodeoxyuridine (BrdU) was used to label dividing cells. Y maze test was used to evaluate the ability of learning and memory. Exercise was conducted in the form of forced running in a motor-driven running wheel. The speed of wheel revolution was regulated at 3 kinds of intensity: lightly running, moderately running, or heavily running. Results Hippocampus lesion could increase the number of BrdU-labeled DG cells, moderately running after lesion could further enhance the number of BrdU-labeled cells and decrease the error number (EN) in Y maze test, while neither lightly running, nor heavily running had such effects. There was a negative correlation between the number of DG BrdU-labeled cells and the EN in the Y maze test after running. Conclusion Moderate exercise could enhance the DG neurogenesis and ameliorate the ability of learning and memory in hippocampus-lesioned rats.     

Distribution pattern and functional state of α1-antichymotrypsin in plaques and vascular amyloid in Alzheimer's disease

Summary Monoclonal antibodies (mAbs) were raised against inactivated 1-antichymotrypsin (ACT) to study the presence and functional state of the serine protease inhibitor 1-antichymotrypsin in cerebral amyloid deposits in Alzheimer's disease. A panel of seven different mAbs was obtained; six of them were directed against neoepitopes that are expressed on ACT after interaction with proteases (inactivated ACT) and one mAb was directed against an epitope that is exposed both on native and inactivated ACT. The mAbs against neoepitopes could discriminate native ACT from complexed and inactivated ACT in vitro as shown in binding experiments in the presence of either native or inactivated ACT. With the mAbs against ACT we found that: (a) besides classical congophilic plaques, amorphous noncongophilic /A4-positive plaques were stained; (b) amorphous and classical plaques reacted with both types of mAbs against ACT indicating that this ACT was either complexed to a protease or proteolytically inactivated; (c) vascular amyloid was not stained for ACT. The presence of ACT in amorphous and classical plaques and its absence in vascular amyloid may indicate differences in the proteolytic degradation of preamyloid into amyloid fibrils. Our study strongly suggests that ACT is biologically active in amyloid plaques from an early stage.Supported by a grant of the Prevention Fund (grant no. 28-1945) and was partly supported by the Faculty of Medicine of the Free University, Amsterdam