Potential of Fibrin Glue and Mesenchymal Stem Cells (MSCs) to Regenerate Nerve Injuries: A Systematic Review.

Cell-based therapy is a promising treatment to favor tissue healing through less invasive strategies. Mesenchymal stem cells (MSCs) highlighted as potential candidates due to their angiogenic, anti-apoptotic and immunomodulatory properties, in addition to their ability to differentiate into several specialized cell lines. Cells can be carried through a biological delivery system, such as fibrin glue, which acts as a temporary matrix that favors cell-matrix interactions and allows local and paracrine functions of MSCs. Thus, the aim of this systematic review was to evaluate the potential of fibrin glue combined with MSCs in nerve regeneration. The bibliographic search was performed in the PubMed/MEDLINE, Web of Science and Embase databases, using the descriptors ("fibrin sealant" OR "fibrin glue") AND "stem cells" AND "nerve regeneration", considering articles published until 2021. To compose this review, 13 in vivo studies were selected, according to the eligibility criteria. MSCs favored axonal regeneration, remyelination of nerve fibers, as well as promoted an increase in the number of myelinated fibers, myelin sheath thickness, number of axons and expression of growth factors, with significant improvement in motor function recovery. This systematic review showed clear evidence that fibrin glue combined with MSCs has the potential to regenerate nervous system lesions.

Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation.

Oxytocin is a well-known neurohypophysial hormone that plays an important role in behavioral anxiety and nociception. Two major forms of long-term potentiation, presynaptic LTP (pre-LTP) and postsynaptic LTP (post-LTP), have been characterized in the anterior cingulate cortex (ACC). Both pre-LTP and post-LTP contribute to chronic-pain-related anxiety and behavioral sensitization. The roles of oxytocin in the ACC have not been studied. Here, we find that microinjections of oxytocin into the ACC attenuate nociceptive responses and anxiety-like behavioral responses in animals with neuropathic pain. Application of oxytocin selectively blocks the maintenance of pre-LTP but not post-LTP. In addition, oxytocin enhances inhibitory transmission and excites ACC interneurons. Similar results are obtained by using selective optical stimulation of oxytocin-containing projecting terminals in the ACC in animals with neuropathic pain. Our results demonstrate that oxytocin acts on central synapses and reduces chronic-pain-induced anxiety by reducing pre-LTP.

Targeted neuromodulation of pelvic floor nerves in aging and multiparous rabbits improves continence.

Pelvic floor muscle stretch injury during pregnancy and birth is associated with the incidence of stress urinary incontinence (SUI), a condition that affects 30-60% of the female population and is characterized by involuntary urine leakage during physical activity, further exacerbated by aging. Aging and multiparous rabbits suffer pelvic nerve and muscle damage, resulting in alterations in pelvic floor muscular contraction and low urethral pressure, resembling SUI. However, the extent of nerve injury is not fully understood. Here, we used electron microscopy analysis of pelvic and perineal nerves in multiparous rabbits to describe the extent of stretch nerve injury based on axon count, axon size, myelin-to-axon ratio, and elliptical ratio. Compared to young nulliparous controls, mid-age multiparous animals showed an increase in the density of unmyelinated axons and in myelin thickness in both nerves, albeit more significant in the bulbospongiosus nerve. This revealed a partial but sustained damage to these nerves, and the presence of some regenerated axons. Additionally, we tested whether electrical stimulation of the bulbospongiosus nerve would induce muscle contraction and urethral closure. Using a miniature wireless stimulator implanted on this perineal nerve in young nulliparous and middle age multiparous female rabbits, we confirmed that these partially damaged nerves can be acutely depolarized, either at low (2-5 Hz) or medium (10-20 Hz) frequencies, to induce a proportional increase in urethral pressure. Evaluation of micturition volume in the mid-age multiparous animals after perineal nerve stimulation, effectively reversed a baseline deficit, increasing it 2-fold (p = 0.02). These results support the notion that selective neuromodulation of pelvic floor muscles might serve as a potential treatment for SUI.

Electrophysiological Activity and Survival Rate of Rats Nervous Tissue Cells Depends on D/H Isotopic Composition of Medium.

The deuterium content modification in an organism has a neuroprotective effect during the hypoxia model, affecting anxiety, memory and stress resistance. The aim of this work was to elucidate the possible mechanisms of the medium D/H composition modification on nerve cells. We studied the effect of an incubation medium with a 50 ppm deuterium content compared to a medium with 150 ppm on: (1) the activity of Wistar rats' hippocampus CA1 field neurons, (2) the level of cultured cerebellar neuron death during glucose deprivation and temperature stress, (3) mitochondrial membrane potential (MMP) and the generation of reactive oxygen species in cultures of cerebellar neurons. The results of the analysis showed that the incubation of hippocampal sections in a medium with a 50 ppm deuterium reduced the amplitude of the pop-spike. The restoration of neuron activity was observed when sections were returned to the incubation medium with a 150 ppm deuterium content. An environment with a 50 ppm deuterium did not significantly affect the level of reactive oxygen species in neuron cultures, while MMP decreased by 16-20%. In experiments with glucose deprivation and temperature stress, the medium with 50 ppm increased the death of neurons. Thus, a short exposure of nerve cells in the medium with 50 ppm deuterium acts as an additional stressful factor, which is possibly associated with the violation of the cell energy balance. The decrease in the mitochondrial membrane potential, which is known to be associated with ATP synthesis, indicates that this effect may be associated with the cell energy imbalance. The decrease in the activity of the CA1 field hippocampal neurons may reflect reversible adaptive changes in the operation of fast-reacting ion channels.

Changes in motor nerve excitability in acute phase Guillain-Barré syndrome.

BACKGROUND: The most common subtypes of Guillain-Barré syndrome (GBS) are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). In the first days after the onset of weakness, standard nerve conduction studies (NCS) may not distinguish GBS subtypes. Reduced nerve excitability may be an early symptom of nerve dysfunction, which can be determined with the compound muscle action potential (CMAP) scan. The aim of this study was to explore whether early changes in motor nerve excitability in GBS patients are related to various subtypes. METHODS: Prospective case-control study in 19 GBS patients from The Netherlands and 22 from Bangladesh. CMAP scans were performed within 2 days of hospital admission and NCS 7-14 days after onset of weakness. CMAP scans were also performed in age- and country-matched controls. RESULTS: CMAP scan patterns of patients who were classified as AMAN were distinctly different compared to the CMAP scan patterns of the patients who were classified as AIDP. The most pronounced differences were found in the stimulus intensity parameters. CONCLUSIONS: CMAP scans made at hospital admission demonstrate several characteristics that can be used as an early indicator of GBS subtype.

A Review of Exercise-Induced Neuroplasticity in Ischemic Stroke: Pathology and Mechanisms.

After ischemic stroke, survivors experience motor dysfunction and deterioration of memory and cognition. These symptoms are associated with the disruption of normal neuronal function, i.e., the secretion of neurotrophic factors, interhemispheric connections, and synaptic activity, and hence the disruption of the normal neural circuit. Exercise is considered an effective and feasible rehabilitation strategy for improving cognitive and motor recovery following ischemic stroke through the facilitation of neuroplasticity. In this review, our aim was to discuss the mechanisms by which exercise-induced neuroplasticity improves motor function and cognitive ability after ischemic stroke. The associated mechanisms include increases in neurotrophins, improvements in synaptic structure and function, the enhancement of interhemispheric connections, the promotion of neural regeneration, the acceleration of neural function reorganization, and the facilitation of compensation beyond the infarcted tissue. We also discuss some common exercise strategies and a novel exercise therapy, robot-assisted movement, which might be widely applied in the clinic to help stroke patients in the future.

Tonic GABAergic Inhibition Is Essential for Nerve Injury-Induced Afferent Remodeling in the Somatosensory Thalamus and Ectopic Sensations.

Peripheral nerve injury induces functional and structural remodeling of neural circuits along the somatosensory pathways, forming the basis for somatotopic reorganization and ectopic sensations, such as referred phantom pain. However, the mechanisms underlying that remodeling remain largely unknown. Whisker sensory nerve injury drives functional remodeling in the somatosensory thalamus: the number of afferent inputs to each thalamic neuron increases from one to many. Here, we report that extrasynaptic γ-aminobutyric acid-type A receptor (GABAAR)-mediated tonic inhibition is necessary for that remodeling. Extrasynaptic GABAAR currents were potentiated rapidly after nerve injury in advance of remodeling. Pharmacological activation of the thalamic extrasynaptic GABAARs in intact mice induced similar remodeling. Notably, conditional deletion of extrasynaptic GABAARs in the thalamus rescued both the injury-induced remodeling and the ectopic mechanical hypersensitivity. Together, our results reveal a molecular basis for injury-induced remodeling of neural circuits and may provide a new pharmacological target for referred phantom sensations after peripheral nerve injury.

From injury to full repair: nerve regeneration and functional recovery in the common octopus, Octopus vulgaris.

Spontaneous nerve regeneration in cephalopod molluscs occurs in a relative short time after injury, achieving functional recovery of lost capacity. In particular, transection of the pallial nerve in the common octopus (Octopus vulgaris) determines the loss and subsequent restoration of two functions fundamental for survival, i.e. breathing and skin patterning, the latter involved in communication between animals and concealment. The phenomena occurring after lesion have been investigated in a series of previous studies, but a complete analysis of the changes taking place at the level of the axons and the effects on the animals' appearance during the whole regenerative process is still missing. Our goal was to determine the course of events following injury, from impairment to full recovery. Through imaging of the traced damaged nerves, we were able to characterize the pathways followed by fibres during regeneration and end-target re-innervation, while electrophysiology and behavioural observations highlighted the regaining of functional connections between the central brain and periphery, using the contralateral nerve in the same animal as an internal control. The final architecture of a fully regenerated pallial nerve does not exactly mirror the original structure; however, functionality returns to match the phenotype of an intact octopus with no observable impact on the behaviour of the animal. Our findings provide new important scenarios for the study of regeneration in cephalopods and highlight the octopus pallial nerve as a valuable 'model' among invertebrates.

Manufacturing of polycaprolactone - Graphene fibers for nerve tissue engineering.

Nanofibrous structures have morphological similarities to extracellular matrix and have been considered as candidate scaffolds in tissue engineering. Scaffolds made from electrospun fibers have potential in cell adhesion, proliferation and cell function. In this study, different percentages of graphene have been dispersed in a polycaprolactone-cyclopentanone solution to produce electrospun fibers. The microstructure and morphology of the fibers and the mechanical behavior of the electrospun systems were evaluated to analyze the influence of graphene content on the performances of the fibers. A significant dimensional difference between the fibers diameters of was obtained due to the graphene percentage. Accordingly, the mechanical properties of the fibrous systems are found to be influenced by the presence of the graphene. Rat stem cells were cultured on the fibrous scaffolds to evaluate the effect of the arrangement of the fibers on the morphology of the cells and differentiation into neurons. In particular, a higher population of dopaminergic neurons has been identified on the fibers with a higher percentage of graphene.

Serial nerve ultrasound and motor nerve conduction studies in chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION: The objective of this study was to evaluate the correlation between cross-sectional area (CSA) and nerve conduction studies (NCS) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to determine how CSA changes over time after standard treatment. METHODS: Fifty-four patients with CIDP were recruited prospectively, and 21 patients were followed for more than 6 months. Ultrasonography and motor NCS were performed in the median and ulnar nerves. RESULTS: No or weak correlation was observed between the maximum CSA and motor conduction velocity. There were segmental nerve enlargements at 61% of sites with conduction block or temporal dispersion. Among 19 patients with clinical improvement after immunotherapy, CSA decreased to normal in 5, increased in 10, and were unchanged in 4. DISCUSSION: Different patterns of CSA and motor NCS changes after immune treatment may indicate different CIDP pathologic mechanisms. Exploration of these pathologic mechanisms could guide treatment choices in the future. Muscle Nerve, 2019.

Warming nerves for excitability testing.

INTRODUCTION: The aim of this study was to find the best method of warming the median nerve before excitability testing to a standard temperature. METHODS: In 5 healthy subjects, the forearm and hand were warmed for 1 h to 37°C by infrared lamp, water blanket, or water bath. Recordings were performed before and during warming every 10 min. Excitability indices were fitted by exponential relations, thereby calculating the time needed to reach 95% of their asymptotic end value. RESULTS: Distal motor latency, refractory period, and superexcitability at 10 ms changed exponentially with time. Warming by water bath took the shortest time (24 min); this was followed by warming by infrared lamp (34 min) and water blanket (35 min). CONCLUSIONS: Warming by water bath is the quickest way. The other methods took only moderately more time. Future studies need to specify both warming method and warming time before excitability testing. Muscle Nerve, 2019.

Carpal tunnel syndrome in advanced age: A sonographic and electrodiagnostic study.

INTRODUCTION: After noting inconsistent sonographic median nerve cross-sectional area (CSA) enlargement at the wrist in very elderly patients with carpal tunnel syndrome (CTS), we systematically reviewed ultrasound, electrodiagnostic, and clinical data collected over a 12-month period in patients from 2 age groups: 80-95 years and 40-65 years old. METHODS: Clinical and electrodiagnostic CTS severity, sensitivity of ultrasound CSA (against both electrodiagnostic and clinical reference standards), and correlations between ultrasound CSA and clinical and electrodiagnostic severity were compared in both groups. RESULTS: In very elderly patients, despite a higher prevalence of severe CTS, nerve ultrasound was less sensitive than in the younger group (54% vs. 87%, using clinical reference standard), and did not correlate with clinical (r = 0.28, P = 0.10) or electrodiagnostic (r = 0.09, P = 0.60) severity. DISCUSSION: Median nerve ultrasound CSA at the wrist is not a sensitive marker of CTS in very elderly populations. In this work we detail and discuss potential pathophysiological underpinnings of this unexpected finding. Muscle Nerve, 2019.

Wide-field corneal subbasal nerve plexus mosaics in age-controlled healthy and type 2 diabetes populations.

A dense nerve plexus in the clear outer window of the eye, the cornea, can be imaged in vivo to enable non-invasive monitoring of peripheral nerve degeneration in diabetes. However, a limited field of view of corneal nerves, operator-dependent image quality, and subjective image sampling methods have led to difficulty in establishing robust diagnostic measures relating to the progression of diabetes and its complications. Here, we use machine-based algorithms to provide wide-area mosaics of the cornea's subbasal nerve plexus (SBP) also accounting for depth (axial) fluctuation of the plexus. Degradation of the SBP with age has been mitigated as a confounding factor by providing a dataset comprising healthy and type 2 diabetes subjects of the same age. To maximize reuse, the dataset includes bilateral eye data, associated clinical parameters, and machine-generated SBP nerve density values obtained through automatic segmentation and nerve tracing algorithms. The dataset can be used to examine nerve degradation patterns to develop tools to non-invasively monitor diabetes progression while avoiding narrow-field imaging and image selection biases.

Pharmacological use of a novel scaffold, anomeric N,N-diarylamino tetrahydropyran: molecular similarity search, chemocentric target profiling, and experimental evidence.

Rational drug design against a determined target (disease, pathway, or protein) is the main strategy in drug discovery. However, regardless of the main strategy, chemists really wonder how to maximize the utility of their new compounds by drug repositioning them as clinical drug candidates in drug discovery. In this study, we started our drug discovery "from curiosity in the chemical structure of a drug scaffold itself" rather than "for a specific target". As a new drug scaffold, anomeric diarylamino cyclic aminal scaffold 1, was designed by combining two known drug scaffolds (diphenylamine and the most popular cyclic ether, tetrahydropyran/tetrahydrofuran) and synthesized through conventional Brønsted acid catalysis and metal-free α-C(sp3)-H functionalized oxidative cyclization. To identify the utility of the new scaffold 1, it was investigated through 2D and 3D similarity screening and chemocentric target prediction. The predicted proteins were investigated by an experimental assay. The scaffold 1 was reported to have an antineuroinflammatory agent to reduce NO production, and compound 10 concentration-dependently regulated the expression level of IL-6, PGE-2, TNF-α, ER-ß, VDR, CTSD, and iNOS, thus exhibiting neuroprotective activity.

[Establishment of pelvic nerve denervation modal in mice].

OBJECTIVE: To establishment and verify pelvic nerve denervation (PND) model in mice. METHODS: (1) Establishment of models. Seventy-two healthy male SPE class C57 mice with age of 7 weeks and body weight of (25±1) g were chosen. These 72 mice were randomly divided into PND group containing 36 mice and sham operation group containing 36 mice. Referring to the establishment method of PND rats, after anesthesia, a laparotomy was performed on the mouse with an abdominal median incision. Under the dissection microscope, the pelvic nerves behind and after each sides of the prostate gland were bluntly separated with cotton swabs and cut with a dissecting scissor. After the operation, the urination of mice was assisted twice every day. For the mice of sham operation group, the pelvic nerves were only exposed without cutting. (2) Detection of models. Colonic transit test was performed in 18 mice chosen randomly from each group to detect the colonic transit ratio (colored colon by methylene blue/ whole colon) and visceral sensitivity tests was performed in the rest mice to observe and record the changes of electromyogram. RESULTS: Three mice died of colonic transit test in each group. Uroschesis occurred in all the mice of PND group and needed bladder massage to assist the urination. Colonic transit test showed that the colonic transit ratios of sham operation group at postoperative day (POD) 1, 3 and 7 were (0.4950±0.3858)%, (0.6386±0.1293)% and (0.6470±0.1088)% without significant difference (F=0.3647, P=0.058), while in PND group, the colonic transit ratio at POD 7 [(0.6044±0.1768) %] was obviously higher than that both at POD 3[(0.3876±0.1364)%, P=0.022] and POD 1[(0.2542±0.0371)%, P=0.001], indicating a recovery trend of colonic transit function (F=9.143, P=0.004). Compared with the sham operation group, the colonic transit function in PND group decreased significantly at POD 1 and POD 3(both P<0.05), and at POD 7, there was no significant difference between two groups. Visceral sensitivity test showed that the visceral sensitivity of sham operation group at POD 1, 3 and 7 was 24.2808±9.5566, 33.6725±7.9548 and 43.9086±12.1875 with significant difference (F=5.722, P=0.014). The visceral sensitivity of PND group at POD 1, 3 and 7 was 11.7609±2.1049, 21.8415±8.1527 and 26.2310±4.2235 with significant difference as well (F=11.154, P=0.001). The visceral sensitivity at POD 3 and POD 7 was obviously higher than that at POD 1 (P=0.006, P<0.001), and there was no significant difference between POD 3 and POD 7 (P=0.183). Compared with sham operation group, the visceral sensitivity of PND group decreased significantly at POD 1, 3 and 7(all P<0.05). CONCLUSIONS: Denervation of pelvic nerves can obviously decrease the colonic transit function and the visceral sensitivity of mice, but these changes can recover over time, which suggests that the establishment of PND model in mice is successful.

Effects of BDNF-Transfected BMSCs on Neural Functional Recovery and Synaptophysin Expression in Rats with Cerebral Infarction.

The purpose of this study was to investigate the effects of brain-derived neurotrophic factor (BDNF)-transfected bone marrow mesenchymal stem cells (BMSCs) on neural functional recovery and synaptophysin expression in rats with cerebral infarction (CI). A total of 120 healthy Sprague Dawley rats were randomly divided into sham group, control group, and model group. Craniotomy was conducted and neurological function defect scoring was used to verify the model. BDNF containing recombinant plasmid was transfected into rat BMSCs, which was verified by flow cytometry and Western Blot. After injection of the transfected BMSCs, neural functional recovery of the CI rats and synaptophysin expression were measured. After the CI rat model was established, magnetic resonance (MR) imaging, 2, 3, 5- triphenyl tetrazolium chloride (TTC) staining, and the neurological function defect scoring determined the success of the model. CD34 (-), CD45 (-), CD29 (+), and CD90 (+) cells detected showed that the obtained BMSCs have high purity. BDNF protein was highly expressed in the BMSCs successfully transfected with the recombinant plasmid. Balance beam walking score, rotating bar walking score, and screen test score were significantly lower, while synaptophysin expression was higher in the BDNF model group than those in the non-BDNF model group and sham group with time extension. BDNF can increase synaptic plasticity and neurogenesis and have a promotional role in neural functional recovery and synaptophysin expression in rats with CI. BDNF-transfected BMSCs may therefore have better treatment efficacy for CI clinically.

Modelling the response to low-frequency repetitive nerve stimulation of myasthenia gravis and Lambert-Eaton myasthenic syndrome.

Myasthenia gravis (MG) is an autoimmune postsynaptic disorder of neuromuscular transmission caused, in most patients, by antibodies against postsynaptic acetylcholine receptors. Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic autoimmune disease in which there is a reduction in Ca2+ entry with each impulse due to the action of antibodies against Ca2+ channels. These diseases have a distinct pattern of response to low-frequency repetitive nerve stimulation which allows its recognition in a particular subject. Nevertheless, the physiologic basis of this response is not entirely known. A model of the time-course of release probability of neuromuscular junctions that incorporates facilitation and a depression-recovery mechanism has been developed with the aim to investigate these response patterns. When the basal value of release probability was in the physiologic range, as in MG, release probability showed an increment after its initial decrease only if the recovery from depression was accelerated by presynaptic residual Ca2+. Otherwise, when the basal release probability was low, as in LEMS, a progressive reduction in the release probability without any late increase was only obtained if the efficacy of Facilitation and Ca2+-dependent recovery from depression were reduced.

Microstructural integrity of the superior cerebellar peduncle is associated with an impaired proprioceptive weighting capacity in individuals with non-specific low back pain.

INTRODUCTION: Postural control is a complex sensorimotor task that requires an intact network of white matter connections. The ability to weight proprioceptive signals is crucial for postural control. However, research into central processing of proprioceptive signals for postural control is lacking. This is specifically of interest in individuals with non-specific low back pain (NSLBP), because impairments in postural control have been observed as possible underlying mechanisms of NSLBP. Therefore, the objective was to investigate potential differences in sensorimotor white matter microstructure between individuals with NSLBP and healthy controls, and to determine whether the alterations in individuals with NSLBP are associated with the capacity to weight proprioceptive signals for postural control. METHODS: The contribution of proprioceptive signals from the ankle and back muscles to postural control was evaluated by local muscle vibration in 18 individuals with NSLBP and 18 healthy controls. Center of pressure displacement in response to muscle vibration was determined during upright standing on a stable and unstable support surface. Diffusion magnetic resonance imaging was applied to examine whether this proprioceptive contribution was associated with sensorimotor white matter microstructure. RESULTS: Individuals with NSLBP showed a trend towards a reduced fractional anisotropy along the left superior cerebellar peduncle compared to healthy controls (p = 0.039). The impaired microstructural integrity of the superior cerebellar peduncle in individuals with NSLBP was significantly correlated with the response to ankle muscle vibration (p<0.003). CONCLUSIONS: In individuals with NSLBP, a decreased integrity of the superior cerebellar peduncle was associated with an increased reliance on ankle muscle proprioception, even on unstable support surface, which implies an impaired proprioceptive weighting capacity. Our findings emphasize the importance of the superior cerebellar peduncle in proprioceptive weighting for postural control in individuals with NSLBP.

Building stable anisotropic tissues using cellular collagen gels.

Combining cellular self-alignment within tethered collagen gels with stabilization through subsequent removal of interstitial fluid has yielded a new process for the fabrication of aligned cellular biomaterials. This commentary discusses the generation of engineered neural tissue for peripheral nerve repair using this combination of techniques, providing additional insight into the rationale underpinning the approach. By describing the potential benefits of using cell and matrix interactions to organize 3D hydrogels that can be stabilized to form tissue-like constructs, the article aims to highlight the potential for the approach to be used in the generation of a wider range of functional replacement tissues.

A systematic review on the nerve-muscle electrophysiology in human organophosphorus pesticide exposure.

This article presents a systematic review of the recent literature on the scientific support of electromyography (EMG) and nerve conduction velocity (NCV) in diagnosing the exposure and toxicity of organophosphorus pesticides (OP). Specifically, this review focused on changes in EMG, NCV, occurrence of intermediate syndrome (IMS), and OP-induced delayed polyneuropathy (OPIDN) in human. All relevant bibliographic databases were searched for human studies using the key words "OP poisoning", "electromyography", "nerve conduction study," and "muscles disorders". IMS usually occurs after an acute cholinergic crisis, while OPIDN occurs after both acute and chronic exposures. Collection of these studies supports that IMS is a neuromuscular junction disorder and can be recorded upon the onset of respiratory failure. Due to heterogeneity of reports on outcomes of interest such as motor NCV and EMG amplitude in acute cases and inability to achieve precise estimation of effect in chronic cases meta-analysis was not helpful to this review. The OPIDN after both acute and low-level prolonged exposures develops peripheral neuropathy without preceding cholinergic toxicity and the progress of changes in EMG and NCV is parallel with the development of IMS and OPIDN. Persistent inhibition of acetylcholinesterase (AChE) is responsible for muscle weakness, but this is not the only factor involved in the incidence of this weakness in IMS or OPIDN suggestive of AChE assay not useful as an index of nerve and muscle impairment. Although several mechanisms for induction of this neurodegenerative disorder have been proposed as were reviewed for this article, among them oxidative stress and resulting apoptosis can be emphasized. Nevertheless, there is little synchronized evidence on subclinical electrophysiological findings that limit us to reach a strong conclusion on the diagnostic or prognostic use of EMG and NCV for acute and occupational exposures to OPs.