Neuropathy In Animals Research Articles

The potential protective effects of pre-injury exercise on neuroimmune responses following experimentally-induced traumatic neuropathy: a systematic review with meta-analysis.

Pre-clinical evidence shows that neuropathy is associated with complex neuroimmune responses, which in turn are associated with increased intensity and persistence of neuropathic pain. Routine exercise has the potential to mitigate complications of future nerve damage and persistence of pain through neuroimmune regulation. This systematic review aimed to explore the effect of pre-injury exercise on neuroimmune responses, and other physiological and behavioural reactions following peripheral neuropathy in animals. Three electronic databases were searched from inception to July 2022. All controlled animal studies assessing the influence of an active exercise program prior to experimentally-induced traumatic peripheral neuropathy compared to a non-exercise control group on neuroimmune, physiological and behavioural outcomes were selected. The search identified 17,431 records. After screening, 11 articles were included. Meta-analyses showed that pre-injury exercise significantly reduced levels of IL-1β (SMD: -1.06, 95% CI: -1.99 to -0.13, n=40), but not iNOS (SMD: -0.71 95% CI: -1.66 to 0.25, n=82). From 72 comparisons of different neuroimmune outcomes at different anatomical locations, vote counting revealed reductions in 23 pro-inflammatory and increases in 6 anti-inflammatory neuroimmune outcomes. For physiological outcomes, meta-analyses revealed that pre-injury exercise improved one out of six nerve morphometric related outcomes (G-ratio; SMD: 1.95, 95%CI: 0.77 to 3.12, n=20) and one out of two muscle morphometric outcomes (muscle fibre cross-sectional area; SMD: 0.91, 95%CI: 0.27 to 1.54, n=48). For behavioural outcomes, mechanical allodynia was significantly less in the pre-injury exercise group (SMD -1.24, 95%CI: -1.87 to -0.61) whereas no overall effect was seen for sciatic function index. Post hoc subgroup analysis suggests that timing of outcome measurement may influence the effect of pre-injury exercise on mechanical allodynia. Risk of bias was unclear in most studies, as the design and conduct of the included experiments were poorly reported. Preventative exercise may have potential neuroprotective and immunoregulatory effects limiting the sequalae of nerve injury, but more research in this field is urgently needed.

Promotion of degradative autophagy by 6-bromoindirubin-3'-oxime attenuates neuropathy.

Damage to the central or peripheral nervous system causes neuropathic pain. Endoplasmic reticulum (ER) stress plays a role in peripheral neuropathy. Increase in ER stress is seen in diabetic neuropathy. Inducers of ER stress also give rise to peripheral neuropathy. ER stress leads to the formation of autophagosome but as their degradation is also stalled during ER stress accumulation of autophagosomes is seen. Accumulation of autophagosomes has deleterious effects on cells. In the present study, we show that treatment with tunicamycin (TM) (ER stress inducer) in mice leads to peripheral neuropathy as assessed by Von Frey and Hot plate method. Administration of a promoter of autophagy viz. 6-bromoindirubin-3'-oxime (6-BIO) subsequent to ER stress induced by TM exhibits a decrease in peripheral neuropathy. 6-BIO was also effective in reducing diabetic peripheral neuropathy. To understand the type of autophagy activated, SH-SY5Y cells were treated with 6-BIO after TM treatment. Levels of cathepsin D (CTSD), a marker for degradative autophagy was higher in cells treated with 6-BIO after TM treatment compared to only TM-treated SH-SY5Y cells while levels of Rab8A,-a marker for secretory autophagy was reduced. Furthermore, in parallel during ER stress secretory, we noted increased levels of lysozyme in autophagosomes destined for secretion. Cells treated with 6-BIO showed reduction of lysozyme in secretory autophagosomes. This shows that 6-BIO increased degradative autophagy and reduced the secretory autophagy. 6-BIO also reduced the caspase-3 activity in 6-BIO-treated cells. Thus, 6-BIO reduced neuropathy in animals by activating degradative autophagy and reducing the secretory autophagy.

Chemopreventive effects of Xiang Sha Liu Jun Zi Tang on paclitaxel-induced leucopenia and neuropathy in animals.

Paclitaxel frequently induces peripheral neuropathy and myelosuppression during cancer treatment. According to the National Health Insurance Research Database of Taiwan, traditional Chinese medicine doctors widely use Xiang Sha Liu Jun Zi Tang (XSLJZT) to treat breast cancer patients who have received paclitaxel. We explored the combined therapeutic effects of XSLZJT with paclitaxel. XSLJZT did not exhibit significant cytotoxic effects on P388-D1 cells; however, the combination of XSLJZT (100 and 500mg/kg) with paclitaxel prolonged the survival rate in P388-D1 tumor-bearing mice compared to paclitaxel-only. In addition, XSLJZT was found to enhance white blood cells (WBC) counts and promote leukocyte rebound in paclitaxel-induced leukopenia in mice. XSLJZT also reduced paclitaxel-induced mechanical pain and inhibited c-Fos protein expression in the L4-6 spinal cords of Wistar rats. Moreover, paclitaxel-induced shortening of the nerve fibers of dorsal root ganglion cells was ameliorated by pre-treatment with XSLJZT. Therefore, we suggest that XSLJZT could be used as an adjunct for cancer patients, as the formula could decrease paclitaxel-induced neuropathy and myelosuppression.

DIET AND ITS MICROENVIRONMENT INFLUENCE THE HEALTH OF COLON

Abstract Ulcerative colitis (UC) is an autoimmune chronic inflammatory disease of the large intestine that greatly increases risks of colorectal cancer. UC is an idiopathic inflammatory disorder of the colonic mucosa, which starts in the rectum and generally extends proximally in a continuous manner through part of, or the entire, colon. A Western diet, smoking, alcohol abuse, altered circadian rhythm and a dysbiotic microbiome is thought to induce UC. However, it is still not completely understood the factors in the diet that triggers UC. Identification of the factors associated with the diet that induce UC will lead to healthier lifestyle that prevents UC. In animal models we show that standard diet and diet rich in fiber positively influenced the health of the colon. A high fat high protein diet negatively regulated the health of the colon. A high fat high protein diet caused obesity in animals, paradoxically it also reduced the colon length significantly in these animals. Animals feeding on a high fat high protein had no energy in the fecal pellet demonstrating peinosis [hunger-like-condition; peina (Greek) hunger; osis (Greek) condition] of the colon. A high fat high protein diet also induced peripheral neuropathy in animals; whereas animals on a high fiber diet was healthy and had longer colon and no peripheral neuropathy. Bacteria of the family Erysipelotrichaceae that is related to inflammation-related disorders of the gastrointestinal tract is also high in animals fed with a high fat high protein diet; these animals also had low levels of valeric acid and propionic acid in the colon. Overall, a high fat high protein diet negatively impacts the health of the colon due to poor energy metabolism and its associated dysbiotic microbiome and metabolome. Currently, anti-inflammatory drugs and immune suppressors are prescribed for UC treatment, side-effects and the risk of opportunistic infections limit the quality of treatment. Hence, there is a need for a new class of biologics for efficient UC treatment. Bin1 is a risk factor in UC as determined by the increase in Bin1 expression in the colon of UC patients. In animal models, we showed that attenuation of BIN1 gene protected against UC. We have developed an innovative therapeutic strategy to treat UC that acts by correcting the leaky colonic epithelial barrier function that drives chronic inflammation in this setting. Specifically, we recently showed that administration of our anti-Bin1 monoclonal antibody (Bin1 mAb 99D) is sufficient to mimic the effect of genetic downregulation of Bin1 to preserve the normal colonic mucosa in an established mouse model of UC, in comparison to control-treated mice which exhibited severe lesions and inflammatory cell influx throughout the mucosa. A diet that positively influence the colon may be beneficial during immunotherapeutic treatment of ulcerative colitis.

Neuroprotective effect of Canthium parviflorum on streptozotocin induced diabetic neuropathy in rats

In traditional system to cure diabetes and related complications, Canthium parviflorum Lam plant leaves are used. Ethanolic extract of leaves were considered to investigate its neuroprotective property in streptozotocin elicited diabetic neuropathy rat model. Streptozotocin (60 mg/kg body weight) given by intraperitoneal injection to induce diabetes, with no treatment given, was intended to develop diabetic neuropathy. Fourteen days after induction, animals were given the extract (100 and 200 mg/kg) once daily for thirty five days. Hypersensitivity to temperature in diabetic neuropathy was assessed by tail immersion and eddy’s hot plate tests. Nerve growth factor, blood glucose, and pro-inflammatory cytokines involved in pathological pain were measured in sciatic nerve. Neuropathy which is also associated with oxidative stress was assessed by measuring bio-markers in sciatic tissue. Diabetic induced neuropathic animals exhibited significant decrease in the paw and tail withdraw time thus signifying diabetic neuropathy. Extract treatment prevented diabetic neuropathy in animals thus showing normalized response to hot and cold. These actions in extract treatment groups are supported evidently by normal blood glucose, significant low levels of pro-inflammatory cytokines, oxidative stress bio-markers, and high nerve growth factor in sciatic nerve tissue. C. parviflorum leaves ethanolic extract display neuroprotective effect in STZ-induced diabetic neuropathy in rats.

Hunting the eagle killer: A cyanobacterial neurotoxin causes vacuolar myelinopathy.

Vacuolar myelinopathy is a fatal neurological disease that was initially discovered during a mysterious mass mortality of bald eagles in Arkansas in the United States. The cause of this wildlife disease has eluded scientists for decades while its occurrence has continued to spread throughout freshwater reservoirs in the southeastern United States. Recent studies have demonstrated that vacuolar myelinopathy is induced by consumption of the epiphytic cyanobacterial species Aetokthonos hydrillicola growing on aquatic vegetation, primarily the invasive Hydrilla verticillata Here, we describe the identification, biosynthetic gene cluster, and biological activity of aetokthonotoxin, a pentabrominated biindole alkaloid that is produced by the cyanobacterium A. hydrillicola We identify this cyanobacterial neurotoxin as the causal agent of vacuolar myelinopathy and discuss environmental factors-especially bromide availability-that promote toxin production.

A lethal combination

Wildlife Disease Although many human activities have clear negative effects on the natural world, there are also unforeseen consequences. Bald eagle mass death events in the southeastern United States may be one such downstream effect of human activity. After considerable effort, Breinlinger et al. identified the cause of these events as an insidious combination of factors. Colonization of waterways by an invasive, introduced plant provided a substrate for the growth of a previously unidentified cyanobacterium. Exposure of this cyanobacterium to bromide, typically anthropogenic in origin, resulted in the production of a neurotoxin that both causes neuropathy in animals that prey on the plants and also bioaccumulates to kill predators such as bald eagles. Science , this issue p. [eaax9050][1] [1]: /lookup/doi/10.1126/science.aax9050

Acute changes in nerve excitability following oxaliplatin treatment in mice.

Oxaliplatin chemotherapy produces acute changes in peripheral nerve excitability in humans by modulating voltage-gated Na+ channel activity. However, there are few animal studies of oxaliplatin-induced neuropathy that demonstrate similar changes in excitability. In the present study, we measured the excitability of motor and sensory caudal nerve in C57BL/6 mice after oxaliplatin injections either systemically (intraperitoneal) or locally (intramuscular at the base of the tail). As opposed to intraperitoneal administration of oxaliplatin, a single intramuscular injection of oxaliplatin produced changes in both motor and sensory axons. In motor axons, oxaliplatin caused a greater change in response to long-lasting depolarization and an upward shift in the recovery cycle, particularly at 24 h [depolarizing threshold electrotonus (TEd) 10-20 ms, P = 0.0095; TEd 90-100 ms, P = 0.0056) and 48 h (TEd 10-20 ms, P = 0.02; TEd 90-100 ms, P = 0.04) posttreatment. Oxaliplatin treatment also stimulated the production of afterdischarges in motor axons. These changes were transient and showed dose dependence. Mathematical modeling demonstrated that these changes could be accounted for by slowing inactivation of voltage-gated Na+ channels by 73.3% and reducing fast K+ conductance by 47% in motor axons. In sensory axons, oxaliplatin caused an increase in threshold, a reduction in peak amplitude, and greater threshold changes to strong hyperpolarizing currents on days 4 and 8. Thus, local administration of oxaliplatin produced clinically relevant changes in nerve excitability in mice and may provide an alternative approach for the study of acute oxaliplatin-induced neurotoxicity.NEW & NOTEWORTHY We present a novel mouse model of acute oxaliplatin-induced peripheral neurotoxicity that is comparable to clinical observations. Intramuscular injection of oxaliplatin produced acute changes in motor nerve excitability that were attributable to alterations in Na+ and K+ channel activity. Conversely, we were unable to show any significant changes in nerve excitability with systemic intraperitoneal injections of oxaliplatin. This study suggests that local intramuscular injection is a valid approach for modelling oxaliplatin-induced peripheral neuropathy in animals.

P.2.045 - A novel role for tau protein in the mechanisms of brain damage caused by peripheral neuropathy

Chronic pain affects approximately 20% of European population and it is now considered a risk factor for different pathologies [1], such as neuropathic pain. Neuropathic pain has been defined by the International Association for the Study of Pain (IASP) as the pain evoked by a lesion or disease of the somatosensory system and is frequently associated with depression and cognitive impairment [1]. However, the underlying cellular mechanisms through which neuropathic pain triggers these behavioural deficits remain unclear. Accumulating evidence suggests the cytoskeletal protein Tau as a key regulator of neuronal plasticity and pathology as Tau hyperphosphorylation and malfunction are involved in several brain pathologies, such as Alzheimer’s disease (AD) [2], excitotoxicity and chronic stress [3], since experimental studies demonstrate that Tau reduction strategies can block both neuronal and behavioural deficits in the above disease conditions [2,3]. Moreover, our previous work suggests Tau involvement in pain mechanisms and circuitry [4]. Based on the above, the present study monitors the potential role of Tau in the establishment of brain structural and behavioural alterations caused by peripheral neuropathy. We have used right spared nerve injury (SNI) model of peripheral neuropathy in animals lacking Tau protein (Tau knockout (Tau-KO)) and their wildtype (WT) littermates. Establishment of the model and pain intensity were monitored using Von Frey test. A battery of behavioural tests was performed at 6 and 12 weeks after SNI surgery to assess locomotion, anxious and depressive-like behaviour as well as cognitive performance. Two-way ANOVA statistical analysis showed no effect of SNI on locomotion or anxiety-like behaviour in all groups on Open field test (F(1.29)=0.020, p=0.888 and F(1.29)=3.29x10-5, p=0.996, respectively). However, SNI caused a depressive-like behaviour in WT, but not Tau-KO, animals as assessed by Forced swimming (F(1.29)=35.04, p Based on the above behavioural and molecular data, this work provides novel evidence regarding Tau’s role on the establishment of depressive behaviour and cognitive deficits triggered by peripheral neuropathy. These results are in line with previous animal studies that show an essential mediation of Tau protein in brain damage in AD as well as chronic stress conditions [2,3] suggesting role for Tau in pathological conditions beyond AD. Furthermore, these studies add to our limited understanding on molecular precipitators of brain deficits caused by chronic pain offering potential therapeutic targets.

Oleo gum resin of Ferula assa-foetida L. ameliorates peripheral neuropathy in mice

Ethnopharmacological relevanceAccording to the Chinese, European, Iranian and Indian traditional medicines, oleo gum resin of Ferula assa-foetida (asafoetida) has therapeutic effects on different kinds of diseases. Some of these effects are related to the diseases of nervous system such as hysteresis and convulsion. In recent studies, some anti-epileptic and neuroprotective roles were also considered for it and we examined its possible role on treatment of peripheral neuropathy. Material and methodsin vitro studies were carried out to identify the response of isolated sciatic nerves to different concentrations of oleo gum resin of asafoetida solved in Lock׳s solution. Then, in vivo studies were conducted to evaluate its effect on amelioration of peripheral neuropathy in mice. Peripheral neuropathy was induced by intraperiotoneal injection of high doses of pyridoxine in adult Balb/c male mice. Tail flick tests were performed to identify the incidence of neuropathy in animals. After 10days treatment with asafoetida, the efficiency of treatment was assessed by behavioral, electrophysiological and histological studies. Resultsin vitro experiments confirmed that incubating the nerves in aqueous extract of oleo gum rein of asafoetida increased the amplitude and decreased the latent period of nerve compound action potential (CAP). Nerve conduction velocity (NCV) and amplitude of CAP also improved in asafoetida treated animals. Histological and behavioral studies showed that asafoetida was able to facilitate the healing process in peripheral nerves. Conclusionsin vitro experiments showed that asafoetida is a nerve stimulant and its administration in neuropathic mice exerted neuroprotecting effects through stimulating axonal regeneration and remyelination and decrement of lymphocyte infiltration.

Attenuating effect of Cilostazol against vincristine – Induced neuropathic pain in mice

BackgroundChemotherapy induced neuropathic pain is a very common adverse effect seen with cancer chemotherapeutic drugs. The activation of BK channels leads to reduced neuronal excitability and suggests its role in the clinical management of pain. The present study investigates the effect of non-selective BK channel activator, Cilostazol (CZ) against vincristine (VC) induced neuropathic pain in mice. MethodsNeuropathic pain was induced in the animals by a single vincristine administration (100 μg/kg, i.v) to all the group of animals. Mice were randomly divided into four groups comprising of a control, two test groups with Cilostazol (20 mg/kg & 40 mg/kg) and a standard group with Gabapentin (GBP, 100 mg/kg). Peripheral neuropathy in animals was verified by mechanical hyperalgesia and mechanical allodynia. Results and discussionControl group did not have any significant effect on mechanical hyperalgesia and mechanical allodynia. Results shows that Cilostazol at both tested dose levels of 5 days administration attenuated mechanical hyperalgesia and mechanical allodynia after the vincristine administration and were comparable with that of Gabapentin. ConclusionThe attenuating effect of Cilostazol in vincristine model suggests that pharmacological activation of BK channel may be potentially useful for managing neuropathic pain.

Toxic neuropathy

This paper examines recent research on toxic neuropathy and potential therapeutic developments. It also summarizes reports of new agents reported to cause peripheral neuropathy. Gene therapy with vasoactive endothelial growth factor, neurotrophic substances such as nerve growth factor and neurotrophin-3 are reported to reverse or protect against neurotoxicity in animal models. The neuroprotective effects of more established therapeutic agents like vitamin E, tacrolimus (FK 506) and erythropoietin hold promise for the immediate future. Cisplatin and high-dose pyridoxine are used more frequently to produce robust models of peripheral neuropathy in animals. Statins do appear to cause peripheral neuropathy. The incidence is low, however, and compared to its benefits in terms of cardiovascular protection, relatively innocuous. The profile of thalidomide neuropathy is becoming clearer as the indications for this drug increases. The incidence of thalidomide neuropathy is high, up to three quarters in some series, and although the information on dose dependency is variable, lower cumulative doses appear to be less toxic. Like thalidomide bortezomib, a novel proteosome inhibitor, is reportedly effective in the treatment of multiple myeloma and is associated with peripheral neuropathy. Oxaliplatin and epothilone are emerging anticancer drugs with neurotoxic potential. Similarly, leflunomide, a new disease modifying-agent approved for the treatment of rheumatoid arthritis, is reported to cause neuropathy. The study of toxic neuropathy is not only enhancing our knowledge of the mechanisms of neurotoxicity but also the neurobiology of peripheral neuropathy in general; and is likely to reveal avenues for therapeutics.

Noscapine crosses the blood-brain barrier and inhibits glioblastoma growth.

The opium alkaloid noscapine is a commonly used antitussive agent available in Europe, Asia, and South America. Although the mechanism by which it suppresses coughing is currently unknown, it is presumed to involve the central nervous system. In addition to its antitussive action, noscapine also binds to tubulin and alters microtubule dynamics in vitro and in vivo. In this study, we show that noscapine inhibits the proliferation of rat C6 glioma cells in vitro (IC(50) = 100 microm) and effectively crosses the blood-brain barrier at rates similar to the ones found for agents such as morphine and [Met]enkephalin that have potent central nervous system activity (P < or = 0.05). Daily oral noscapine treatment (300 mg/kg) administered to immunodeficient mice having stereotactically implanted rat C6 glioblasoma into the striatum revealed a significant reduction of tumor volume (P < or = 0.05). This was achieved with no identifiable toxicity to the duodenum, spleen, liver, or hematopoietic cells as determined by pathological microscopic examination of these tissues and flow cytometry. Furthermore, noscapine treatment resulted in little evidence of toxicity to dorsal root ganglia cultures as measured by inhibition of neurite outgrowth and yielded no evidence of peripheral neuropathy in animals. However, evidence of vasodilation was observed in noscapine-treated brain tissue. These unique properties of noscapine, including its ability to cross the blood-brain barrier, interfere with microtubule dynamics, arrest tumor cell division, reduce tumor growth, and minimally affect other dividing tissues and peripheral nerves, warrant additional investigation of its therapeutic potential.

Pharmacokinetics of acrylamide after oral administration in male rats

Acrylamide (AMD) is a commonly used industrial chemical. However, it produces a dying back type of peripheral neuropathy in animals and man. This study was performed to investigate the pharmacokinetics of AMD after oral administration at 50 mg/g ([1- 14C]AMD) in male Sprague-Dawley rats. Absorption from the gastrointestinal tract was rapid and radioactivity was detected in blood 5 min post-administration. The peak plasma concentration occurred 38 min after administration and was equivalent to 47 μg/ml. The elimination pattern for plasma was fitted to a one-compartment model with 6 h half-life. However, in the blood the elimination pattern was fitted to a two-compartment model with 7.93 and 374 h for distribution and elimination phases, respectively. Tissue concentrations of radioactivity determined at 28 and 144 h post-administration differed substantially. After 28 h the highest activity was in the gastric content, followed by stomach, lung, bone marrow and skin, while after 144 h the order of total radioactivity was lung>bone marrow>esophagus. The activities in the rest of the organs in both experiments were very low. The excretion study revealed that the kidney is the major route of elimination and the majority of radioactivity in urine was excreted during the first 12 h. The feces contained approximately 10% of the administered dose after 144 h. This study indicated that AMD is rapidly absorbed from the rat's gastrointestinal tract, distributed and eliminated from the body. AMD bound but did not accumulate in the erythrocytes or the neural tissues.

Specificity and structure of murine monoclonal antibodies against GM1 ganglioside

Anti-GM1 antibodies have been implicated in the pathogenesis of several neurological diseases, but the role of these antibodies is still controversial. An animal model could provide insight into the mechanisms of these human disorders, but obtaining specific anti-GM1 monoclonal antibodies (mAbs) has been extremely difficult because of the weak immunogenicity of GM1 ganglioside. Four murine mAbs against GM1 were elecited by immunization of mice with lyso GM1 coupled to BSA and GM1 glycolipid. All four IgM,k mAbs bound strongly to GM1, three antibodies (125, 360 and 494) also bound very weakly to asialo GM1 (GA1) and one (156) bound weakly to GD1b. Three antibodies (125, 360 and 494) were encoded by the same V H and V K genes. The V H gene exhibited 97% homology to V HOX1, a member of the V HQ52N gene family, the D segment was probably derived from DQ52 and J H was identical to J H2. The V K gene was approximately 99% homologous to V KRF and J K was germline J K2. The V H gene of mAb 156 exhibited 98% homology to V H205.12, of the V HJ558 gene family, the D segement was derived from DFL16.1, and J H was germline J H2. The V K and J K genes of mAb 156 were identical to V K8 and J K1, respectively. The genes encoding these anti-GM1 antibodies were close to germline sequences and have been used to encode other antibodies. This suggests that the unresponsiveness of mice to immunization is probably due to inactivation of self-reactive B cells. These rare anti-GM1 mAbs will be valuable reagents for studies of the pathogenesis of autoimmune neuropathy in animals, and also for analyzing the tissue distribution and functions of GM1.

Antibody responses to P 0 and P 2 myelin proteins in Guillain-Barré syndrome and chronic idiopathic demyelinating polyradiculoneuropathy

Immunisation with the peripheral nerve myelin proteins P 0 or P 2 induces inflammatory neuropathy in animals. We sought antibodies with an ELISA to these proteins in 38 patients with acute Guillain-Barré syndrome (GBS), 32 patients with chronic idiopathic demyelinating polyradiculoneuropathy (CIDP), 31 patients with other neuropathies (ONP) and 26 normal control (NC) subjects. We discovered IgM antibodies to human P 0 protein in the sera of 18.5% of the patients with GBS, 15.6% with CIDP, 6.4% with ONP and 3.8% of NC subjects. Of the sera which reacted with P 0, sera from 4 7 of GBS, 3 5 of CIDP, 1 2 of ONP patients and 0/1 of NC subjects reacted with a synthetic P 0 peptide representing residues 150–169 from the cytoplasmic portion of the molecule. IgG antibodies to P 0 were slightly less common than IgM antibodies, being present in only 7.9% of GBS, 0% of CIDP and 3% of ONP patients and 0% of NC subjects. We found antibodies to bovine P 2 protein more commonly than antibodies to P 0. IgM antibodies were present in 39.5% of GBS, 34.4% of CIDP, 16.1% of ONP patients and 15.4% of NC subjects. IgG antibodies were present in 18.4% of GBS, 12.5% of CIDP, 3.2% of ONP patients and 7.6% of NCs. Of the sera which contained antibodies to P 2 protein, only a few reacted with P 2 peptides 14–25 or 58–81, but without any consistent pattern of reactivity. We propose that IgM antibodies to P 0 may contribute to the demyelination in some cases of GBS and CIDP, whereas the more commom antibodies to P 2 may merely be markers of a simultaneous pathogenetic T cell-mediated response.

The toxicity of acrylamide (author's transl)

Acute and chronic toxicities of acrylamide (AAM) are reviewed with special reference to its dose-response relationship from literature concerning the general toxicology and industrial hygiene. Although the total doses of AAM for producing chronic neuropathy in animals showed considerable variation among literature sources, estimated mean concentrations of the compound in the nervous tissues do not seem to differ very much at any stage of the poisoning. Reports of human poisoning, most of them being due to occupational exposure, are referred and symptoms of the poisoning are summarized from these cases.

Biochemical studies on acrylamide, a neurotoxic agent

Acrylamide produces peripheral neuropathy in animals and therefore an examination has been made of its biochemical properties. It is inactive against the normal energy producing mechanisms. Using 1-[ 14C]acrylamide it has been shown that it reacts in vivo and in vitro with non-protein sulphydryl and with proteins of rat tissue. Labelling of the proteins in the central nervous system persists for more than 14 days. The reactivity of many unsaturated compounds with glutathione has been measured. The reactivity of N-(hydroxymethyl) acrylamide is identical to that of acrylamide; after administration of 1-[ 14C]- N-(hydroxymethyl)acrylamide and 1-[ 14C]acrylamide to rats, tissues are labelled in a similar manner. In contrast to this similar reactivity, N-(hydroxymethyl) acrylamide does not produce peripheral neuropathy. The relevance of these observations to future work on the mechanism of the biological specificity of acrylamide is discussed.

The Guillain-Barré syndrome. Relationship of circulating immunocytes to disease activity.

THE Guillain-Barre syndrome (GBS) is an acute polyneuropathy of humans characterized histologically by mononuclear cell infiltrates and segmental demyelination. 1-3 Although described initially by Landry 4 in 1859, and Guillain et al 5 in 1916, the etiology and pathogenesis of this important disorder still remain unknown. In 1955, Waksman and Adams 6 described a peripheral neuropathy in animals, experimental allergic neuritis (EAN), produced by the injection of peripheral nervous tissue in complete Freund's adjuvant. Because of the similar clinical and pathologic features in this immune-mediated experimental disease, and the GBS, a common mechanism of tissue injury was postulated. Recent studies have shown that increased numbers of atypical basophilic mononuclear cells, many of which are synthesizing DNA, occur in peripheral blood during immune reactions. 7-9 These circulating sensitized cells, or immunocytes, are presumed to mirror the intense concomitant proliferation occurring in the host's lymphoid tissues. Circulating immunocytes have also