Multi Omics Applications in Biological Systems.

Traditional methodologies often fall short in addressing the complexity of biological systems. In this regard, system biology omics have brought invaluable tools for conducting comprehensive analysis. Current sequencing capabilities have revolutionized genetics and genomics studies, as well as the characterization of transcriptional profiling and dynamics of several species and sample types. Biological systems experience complex biochemical processes involving thousands of molecules. These processes occur at different levels that can be studied using mass spectrometry-based (MS-based) analysis, enabling high-throughput proteomics, glycoproteomics, glycomics, metabolomics, and lipidomics analysis. Here, we present the most up-to-date techniques utilized in the completion of omics analysis. Additionally, we include some interesting examples of the applicability of multi omics to a variety of biological systems.

Effect of Leuprolide Acetate, a GnRH Agonist, on Neuroinflammation and Anxiety-Like Behavior after Mild Hypoxic-Ischemic Encephalopathy in Rat Model.

BACKGROUND: Mild hypoxic-ischemic encephalopathy (HIE) is a condition that predisposes to negative outcomes such as neuroanatomical injury, mood disorders, and motor or cognitive disabilities. The neuroinflammation plays an important role in the neurological damage; therefore, reducing it could provide neuroprotection. The leuprolide acetate (LA) has shown to have neuroregenerative and immunomodulator properties in other nervous system injuries. OBJECTIVE: The aim of this study was to evaluate the immunomodulatory effect of LA in the acute phase of mild HIE and its effects in motor activity and behavior in a subacute phase. METHOD: Forty-five Wistar rats on postnatal day 7 were divided into Sham, HIE treated with saline solution (HIE-SS), and HIE-LA. The HIE was performed cutting of the right carotid artery followed by 60 min of hypoxia. The expression of the inflammatory cytokines interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and the chemokine CXCL-1 were evaluated 72 h after HIE by RT-qPCR and the motor activity and behavior were evaluated by open field test at postnatal day 33. RESULTS: HIE-SS animals showed increased expression of IL-1ß, TNF-α, IFN-γ, and CXCL-1 genes in injured tissue. However, the HIE-LA group exhibited similar expression levels of IL-1ß and TNF-α to the Sham group, while IFN-γ and CXCL-1 mRNA expression were attenuated with LA treatment. LA treatment also prevented anxiety-like behavior in the open field test. CONCLUSION: Treatment with LA partially reverses HIE-induced neuroinflammation and prevents anxiety-like behavior in neonatal rats.

Bioactive role of vitamins as a key modulator of oxidative stress, cellular damage and comorbidities associated with spinal cord injury (SCI).

Introduction: Spinal cord injury (SCI) cause significant disability and impact the quality of life of those affected by it. The nutritional status and diet are fundamental to diminish the progression of complications; vitamins modulate the inflammatory response and oxidative stress, promote blood-spinal cord barrier preservation and the prompt recovery of homeostasis. A deep knowledge of the benefits achieved from vitamins in patients with SCI are summarized. Information of dosage, time, and effects of vitamins in these patients are also displayed. Vitamins have been extensively investigated; however, more clinical trials are needed to clarify the scope of vitamin supplementation.Objective: The objective of this review was to offer relevant therapeutic information based on vitamins supplementation for SCI patients.Methods: Basic and clinical studies that have implemented the use of vitamins in SCI were considered. They were selected from the year 2000-2022 from three databases: PubMed, Science Direct and Google Scholar.Results: Consistent benefits in clinical trials were shown in those who were supplemented with vitamin D (prevents osteoporosis and improves physical performance variables), B3 (improves lipid profile) and B12 (neurological prophylaxis of chronic SCI damage) mainly. On the other hand, improvement related to neuroprotection, damage modulation (vitamin A) and its prophylaxis were associated to B complex vitamins supplementation; the studies who reported positive results are displayed in this review.Discussion: Physicians should become familiar with relevant information that can support conventional treatment in patients with SCI, such as the use of vitamins, a viable option that can improve outcomes in patients with this condition.

Neonatal Hypoxic-Ischemic Encephalopathy: Perspectives of Neuroprotective and Neuroregenerative Treatments.

Hypoxic-ischemic encephalopathy (HIE) is a serious condition that could have deleterious neurological outcomes, such as cerebral palsy, neuromotor disability, developmental disability, epilepsy, and sensitive or cognitive problems, and increase the risk of death in severe cases. Once HIE occurs, molecular cascades are triggered favoring the oxidative stress, excitotoxicity, and inflammation damage that promote cell death via apoptosis or necrosis. Currently, the therapeutic hypothermia is the standard of care in HIE; however, it has a small window of action and only can be used in children of more than 36 gestational weeks; for this reason, it is very important to develop new therapies to prevent the progression of the hypoxic-ischemic injury or to develop neuroregenerative therapies in severe HIE cases. The objective of this revision is to describe the emerging treatments for HIE, either preventing cell death for oxidative stress, excitotoxicity, or exacerbated inflammation, as well as describing a new therapeutic approach for neuroregeneration, such as mesenchymal stem cells, brain-derived neurotrophic factor, and gonadotropin realizing hormone agonists.

Gonadotropin-Releasing Hormone Receptor Expression in Human Spinal Cord.

The expression of the gonadotrophin-releasing hormone receptor expression on pituitary gonadotrophs in humans is well characterized. In nervous system they have also been found in hippocampi and cerebral cortex. However, gonadotrophin-releasing hormone receptor expression in human spinal cord has not been reported. This study was to analyze the gonadotrophin-releasing hormone receptor expression in human spinal cord by immunohistochemistry, mRNAs by reverse transcriptase polymerase chain reaction, cDNA cloning and Western blot. The results show immunoreactive material to gonadotrophin-releasing hormone receptor in motoneurons of the spinal cord. Further, the study revealed that spinal cord expressed the gonadotrophin-releasing hormone receptor mRNA. The amplicon sequence corresponds to 100% of identity to GenBank. In Western blot, a band of 37 kDa were found in extracts of spinal cord and placenta as a control. In conclusion, human spinal cord expresses gonadotrophin-releasing hormone receptor analyzed through immunohistochemistry, the expression of its mRNA, cloning its cDNA and Western blot analysis. The presence of gonadotrophin-releasing hormone receptor in the spinal cord suggests the possibility of an extrapituitary functional role independent of reproductive system.

Therapeutic approaches of trophic factors in animal models and in patients with spinal cord injury.

Trophic factors are naturally produced by different tissues that participate in several functions such as the intercellular communication, in the development, stability, differentiation and regeneration at the cellular level. Specifically, in the case of spinal injuries, these factors can stimulate neuronal recovery. They are applied both in experimental models and in clinical trials in patients. The trophic factors analysed in this review include gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), growth hormone (GH), melatonin, oestrogens, the family of fibroblast growth factors (FGFs), the family of neurotrophins and the glial cell-derived neurotrophic factor (GDNF). There are some trophic (neurotrophic) factors that already been tested in patients with spinal cord injury (SCI), but only shown partial recovery effect. It is possible that, the administration of these trophic factors together with physical rehabilitation, act synergistically and, therefore, significantly improve the quality of life of patients with SCI.

Leuprolide Acetate, a GnRH Agonist, Improves the Neurogenic Bowel in Ovariectomized Rats with Spinal Cord Injury.

BACKGROUND: Electromyographic studies have shown that external anal sphincter activity is modified in response to distension in animals with spinal cord injury. Gonadotropin-releasing hormone and its agonist leuprolide acetate have neurotrophic properties in animals with spinal cord injury. AIM: This study was to determine the effects of leuprolide acetate treatment on electromyographic activity of the external anal sphincter and anorectal manometry in ovariectomized rats with spinal cord injury. METHODS: Adult ovariectomized rats were divided in three groups: (a) sham of spinal cord injury, (b) spinal cord injury treated with saline solution, and (c) spinal cord injury treated with leuprolide acetate. The spinal cord injury was induced by clamping at level T9. Leuprolide acetate dosage of 10 µg/kg was proctored intramuscular for 5 weeks, commencing the day after the lesion. Electromyography of the external anal sphincter, anorectal manometry, and volume of the cecum were evaluated in all groups. RESULTS: The electromyographic study of the external anal sphincter activity showed a significant improvement in injured rats treated with leuprolide acetate. Manometric analysis and cecum volume data obtained in animals with leuprolide acetate were very similar to those found in the sham group. CONCLUSIONS: These results demonstrate that leuprolide acetate treatment improves the neurogenic colon in ovariectomized rats with spinal cord injury.

Chronic administration of gonadotropin releasing-hormone improves learning in old gonadectomized rats.

The aim of this study was to determine whether chronic administration of GnRH improves performance of learning tasks and expression of spinophilin in the hippocampus of gonadectomized old rats. Eighteen-month-old male Wistar rats were used and divided into three groups: control (intact rats); gonadectomized; and gonadectomized + GnRH. The latter group was injected intramuscularly with GnRH (100 nM) twice a day for five weeks. The learning tasks we used were the novel object recognition task (NOR), elevated T-maze (ETM) and active avoidance test (AAT). Results showed that in NOR and ETM learning tasks, gonadectomized rats treated with GnRH had a significantly better performance than gonadectomized rats without treatment. GnRH-treated gonadectomized rats displayed performance comparable to that of intact rats. Furthermore, the expression of spinophilin in the hippocampus of gonadectomized rats treated with GnRH increased with respect to untreated gonadectomized rats. In conclusion, the chronic administration of GnRH improves learning in old gonadectomized rats. It is possible that the mechanism could involve a greater number of dendritic contacts associated with a higher expression of spinophilin.

Administration of leuprolide acetate, a GnRH agonist, improves urodynamic parameters in ovariectomized rats.

AIM: To evaluate the effects of a treatment with leuprolide acetate (LA) on bladder overactivity as well as the expression of gonadotropin releasing hormone receptor (GnRH-R), and neurofilaments NF68 and NF200 in female rats with overactive bladder induced by castration. METHODS: Changes in the urodynamic parameters were determined in SHAM, ovariectomized (OVX) and ovariectomized rats treated with LA (OVX-LA). A semi-quantitative analysis for the expression pattern of GnRH-R and neurofilaments NF68 and NF200 were determined. RESULTS: Forty-three days after ovariectomy, rats from the OVX group have significant lower values for intercontractile interval (ICI) and compliance (C); as well as higher values for basal bladder pressure (BP) and frequency of non-voiding contractions (NVC). The systemic application of LA increased voiding volume (Vv) and pressure threshold (ThP) in the OVX-LA animals. The application of LA reduced the high frequency of NVC in the OVX rats. No significant differences were found for Vv and NVCs between the OVX-LA vs SHAM groups. At the mid part of the bladder, the presence of GnRH-R was evidenced in the urothelium of the SHAM group. The OVX animals showed different pattern of immunolabeling for GnRH-R as well as for neurofilaments NF200 and NF68, whereas in the OVX-LA group the immunofluorescence pattern was similar to the one seen in SHAM bladders (P < 0.05 for OVX vs OVX + LA). CONCLUSIONS: the results suggest that systemic application of LA can improve bladder dysfunction in castrated rats, and perhaps considered as a treatment for overactive bladder conditions secondary to menopause.

Effects of GnRH on Neurite Outgrowth, Neurofilament and Spinophilin Proteins Expression in Cultured Spinal Cord Neurons of Rat Embryos.

It has been previously described the presence of GnRH receptor in spinal cord neurons of rat embryos and adult rats. However, the functional role of these receptors has not been studied. In this work, the effect of GnRH on neurite outgrowth and cytoskeletal protein expression in cultured spinal cord neurons of rat embryos was analyzed. Specifically, neurofilaments of 68 and 200 kDa by immunoblot assays and spinophilin mRNA expression by RT-PCR. Results show that GnRH stimulates neurite outgrowth in addition to an increase in neurofilaments and spinophilin expression. These findings suggest that GnRH may play a role as neuromodulator in neuronal plasticity and that could be considered as a potential factor for neuronal regeneration in spinal cord injuries.

Leuprolide Acetate Inhibits Spinal Cord Inflammatory Response in Experimental Autoimmune Encephalomyelitis by Suppressing NF-κB Activation.

OBJECTIVE: Recent findings have shown that gonadotropin-releasing hormone (GnRH) administration in an animal model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE) improves clinical signs of locomotion. The present study was designed to determine whether the administration of the synthetic analog of GnRH, leuprolide acetate (LA) - besides its effects on clinical signs of locomotion - also has an effect on the activation/expression levels of molecular markers of EAE, namely transcription nuclear factor (NF)-κB and the proinflammatory cytokines IL-1ß, IL-17A, IL-23 and TNF-α. METHODS: EAE spinal cords were collected from control and LA-administered rats. Lumbar sections were processed at four different time points during the course of the disease to analyze NF-κB activation by chemiluminescent Western blot, and during the EAE recovery phase to evaluate proinflammatory cytokine levels by quantitative real-time PCR. RESULTS: It was found that LA administration to EAE rats promoted a significant reduction of NF-κB activation during the course of the disease and also decreased the mRNA expression levels of the proinflammatory cytokines IL-1ß, IL-17A and TNF-α in the EAE recovery phase; both effects are consistent with the decrease in the severity of clinical signs of locomotion induced by the treatment. CONCLUSION: LA causes a reduction in the severity of locomotor activity, as well as in the activation of NF-κB and the number of proinflammatory markers in rats with EAE. These results suggest the use of this agonist as a potential therapeutic approach for multiple sclerosis.

Functional and structural recovery of the injured spinal cord in rats treated with gonadotropin-releasing hormone.

Several studies have shown that gonadotropin-releasing hormone (GnRH) have extra-pituitary roles, including neurotrophic effects. This study was to evaluate the effects of GnRH treatment on the spinal cord injury (SCI) of rats. Ovariectomized rats were divided into: sham SCI surgery (Sham), SCI treated with saline solution (SCI + SS), and SCI treated with GnRH (SCI + GnRH). The SCI was induced by compression. One day after the lesion, SCI + GnRH group was injected with GnRH (60 µg/kg/twice/day; i.m.) for 15 days and the other groups with saline solution. To kinematic gait analysis, length and velocity of the stride were measured. In spinal cord, axonal morphometry and spared white and gray matter were analyzed by histochemistry. Protein expression of spinophilin was evaluated by western blot. The results showed that, 5 weeks after the injury, the group of animals treated with GnRH, significantly increased the length and velocity of the stride compared to SCI + SS group and they were similar to Sham group. In spinal cord, GnRH treatment increased the number and caliber of nerve axons and in the case of white matter, spared tissue was significantly higher than those animals treated with saline solution. The expression of spinophilin in spinal cord of SCI + GnRH group was slightly increased with respect to those not treated. In conclusion, GnRH treatment improves recovery of gait and decreases histopathological damage in the injured spinal cord of rat. These findings suggest that GnRH acts as a neurotrophic factor and can be used as a potential therapeutic agent for treatment of SCI.

Inhibition of Tumor Growth and Metastasis by Newcastle Disease Virus Strain P05 in a Breast Cancer Mouse Model.

PURPOSE: Conventional therapies and surgery remain the standard treatment for breast cancer. However, combating the eventual development of metastasis is still a challenge. Newcastle disease virus (NDV) is one of the various species of viruses under clinical evaluation as a vector for oncolytic, gene-, and immune-stimulating therapies. The purpose of this study was to evaluate the antitumor activity of a recombinant NDV (rNDV-P05) in a breast cancer murine model. METHODS: Tumors were induced by injecting the cellular suspension (4T1 cell line) subcutaneously. The virus strain P05 was applied three times at intervals of seven days, starting seven days after tumor induction, and was completed 21 days later. Determination of tumor weight, spleen index, and lung metastasis were done after sacrificing the mice. Serum levels of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, and TNF-related apoptosis-inducing ligand (TRAIL) were quantified by enzyme-linked immunosorbent assay. CD8+ infiltrated cells were analyzed by immunofluorescence. RESULTS: rNDV-P05 showed a route-of-administration-dependent effect, demonstrating that the systemic administration of the virus significantly reduces the tumor mass and volume, spleen index, and abundance of metastatic clonogenic colonies in lung tissue, and increases the inhibition rate of the tumor. The intratumoral administration of rNDV-P05 was ineffective for all the parameters evaluated. Antitumor and antimetastatic capability of rNDV-P05 is mediated, at least partially, through its immune-stimulatory effect on the upregulation of TNF-α, TRAIL, IFN-α, and IFN-γ, and its ability to recruit CD8+ T cells into tumor tissue. CONCLUSION: Systemic treatment with rNDV-P05 decreases the tumoral parameters in the breast cancer murine model.

Analysis of hippocampus in rats with acute brain ischemia-reperfusion injury treated with leuprolide acetate, an agonist of GnRH.

BACKGROUND: The hippocampus is highly vulnerable to damage in the brain ischemia-reperfusion injury model. Leuprolide acetate has been shown to promote neurological recovery after injury in various regions of the central nervous system. OBJECTIVE: The objective of this study was to assess the histology of the hippocampus and the expression of neuronal recovery markers, specifically the 200 kDa neurofilaments and the myelin basic protein, in rats with brain ischemia-reperfusion injury treated with leuprolide acetate. METHODS: The rats were divided into three groups: Sham, ischemia-reperfusion with saline solution, and ischemia-reperfusion treated with leuprolide acetate. Coronal brain slices were obtained and stained with hematoxylin-eosin. The histological analysis involved quantifying the number of neurons in the hippocampal regions CA1, CA3 and DG. The myelin basic protein and neurofilaments were quantified using western blot. RESULTS: The number of neurons in CA1 and DG was significantly higher in the leuprolide acetate group compared to the untreated group. Additionally, the expression of neurofilament and myelin basic protein markers was significantly increased in rats treated with leuprolide acetate compared to the untreated rats. CONCLUSIONS: Leuprolide acetate promotes the recovery of hippocampal neurons in an acute brain ischemia-reperfusion injury model. These findings suggest that leuprolide acetate could be a potential therapeutic intervention for reversing damage in hippocampal ischemic lesions.

Leuprolide acetate, a GnRH agonist, improves experimental autoimmune encephalomyelitis: a possible therapy for multiple sclerosis.

Gonadotrophin-releasing hormone (GnRH), a well known hypothalamic neuropeptide, has been reported to possess neurotrophic properties. Leuprolide acetate, a synthetic analogue of GnRH is considered to be a very safe and tolerable drug and it has been used for diverse clinical applications, including the treatment of prostate cancer, endometriosis, uterine fibroids, central precocious puberty and in vitro fertilization techniques. The present study was designed to determine whether Leuprolide acetate administration, exerts neurotrophic effects on clinical signs, body weight gain, neurofilaments (NFs) and myelin basic protein (MBP) expression, axonal morphometry and cell infiltration in spinal cord of experimental autoimmune encephalomyelitis (EAE) rats. In this work, we have found that Leuprolide acetate treatment decreases the severity of clinical signs of locomotion, induces a significantly greater body weight gain, increases the MBP and NFs expression, axonal area and cell infiltration in EAE animals. These results suggest the use of this agonist as a potential therapeutic approach for multiple sclerosis.

Comparing toxicity endpoints on Lecane quadridentata (Rotifera: Monogononta) exposed to two anticholinesterases pesticides.

Toxicity tests were performed on the freshwater rotifer Lecane quadridentata exposed to the pesticides carbaryl and methyl parathion (lethal, sublethal, and chronic) to compare the sensitivity between different endpoints: (a) 48-h mortality; (b) 30-min in vivo inhibition of esterase activity; (c) 5-day inhibition of the instantaneous growth rate. The emphasis of this work was to find the most appropriate endpoint to evaluate the toxicity of these pesticides in view of their sensitivity, duration, and ecological relevance. The comparison between the three toxicity tests show that the 5-day chronic tests have the lowest EC50 (2.22 and 6.6 mg/L), lowest-observed-effect concentration (2.5 and 2.5 mg/L), and no-observed-effect concentration (1.0 and 1.2 mg/L) values for carbaryl and methyl parathion, respectively. This indicates that the estimate of the instantaneous rate of natural increase r is the most sensitive endpoint regarding the toxicity of these pesticides. This sensitivity might be due to the effect on reducing the growth potential form the first generation on. Lethal and sublethal tests are closely related, suggesting that the immediate effect after inhibition of esterases is death. In general, the sensitivity of L. quadridentata is similar to other species of rotifers exposed to methyl parathion. Therefore, the 5-day chronic toxicity test with the freshwater rotifer L. quadridentata should be considered a good candidate to evaluate the effect of anticholinesterase pesticides, due to its high sensitivity and ecological relevance.

Continuous administration of leuprolide acetate improves urinary function in male rats with severe thoracic spinal cord injury.

AIMS: To determine if a continuous administration of leuprolide acetate (LA), a synthetic agonist for the gonadotrophin-releasing hormone receptor, facilitates the recovery of urinary function in spinal cord injured male rats. MAIN METHODS: Male Wistar rats were randomized into spinal cord injury (SCI; n = 7), SCI with continuous administration of LA for two weeks via implantation of a subcutaneous osmotic pump (SCI + LA; n = 7), Sham SCI (SH-SCI; n = 6) or no surgery (Intact; n = 6) groups. Micturition, hind-limb nociception and locomotor behaviors were analyzed before and after surgical procedures on days 7, 14, 21 and 28. After behavioral studies, electromyography of the external urethral sphincter (EUS-EMG) and cystometric (CMG) studies were performed in all groups. KEY FINDINGS: SCI significantly decreased frequency of voids and CMG parameters (p < 0.001), abolished the bursting activity of the EUS during CMG, significantly increased hind limb sensory threshold and decreased locomotor performance in comparison to the other groups (p < 0.001). Continuous LA treatment significantly increased the frequency of voids and improved CMG parameters (p < 0.001), exhibiting bursting EUS activity during CMGs, and enhanced locomotor performance in comparison to SCI rats (p < 0.001). SIGNIFICANCE: SCI severely affected behavioral and functional micturition processes, including sensory and locomotor functions. Systemic and uninterrupted treatment with LA improves the recovery of micturition behavior and the synergistic function of the EUS. Furthermore, sensory and locomotor responses were also improved in SCI rats. This procedure may have a therapeutic potential to facilitate urinary function recovery in patients with SCI.

Central GPR55 may prevent nicotine reinforcing actions: a preliminary study.

GPR55 is an orphan receptor whose endogenous agonists include lysophosphatidylinositol (LPI) and N­acetylethanolamides (NAEs), such as palmitoylethanolamide (PEA) and anandamide. Furthermore, its physiology in the central nervous system involves motor coordination, procedural and spatial memory, pain, and anxiety, among others. Recent reports indicate that systemic injections of O­1602 (a GPR55 and GPR18 agonist) blocked the reinforcing effects of morphine and nicotine in the conditioned place preference (CPP) paradigm, suggesting a possible participation of peripheral and/or central GPR55/GPR18 in brain reward/anti­reward systems. In this pilot study, the endogenous GPR55 agonists LPI and PEA, the highly selective GPR55 synthetic agonist ML184 or the selective GPR55 antagonist ML193 were injected to examine their pharmacological effects on the reinforcing actions of nicotine in the CPP paradigm. Our preliminary study shows that injections of LPI, PEA, ML184 and ML193 interfered with the change in place preference induced by nicotine via mechanisms that remain to be identified (which probably include central GPR55).

Pixel-Wise Classification in Hippocampus Histological Images.

This paper presents a method for pixel-wise classification applied for the first time on hippocampus histological images. The goal is achieved by representing pixels in a 14-D vector, composed of grey-level information and moment invariants. Then, several popular machine learning models are used to categorize them, and multiple metrics are computed to evaluate the performance of the different models. The multilayer perceptron, random forest, support vector machine, and radial basis function networks were compared, achieving the multilayer perceptron model the highest result on accuracy metric, AUC, and F 1 score with highly satisfactory results for substituting a manual classification task, due to an expert opinion in the hippocampus histological images.

Recovery of sciatic nerve with complete transection in rats treated with leuprolide acetate: A gonadotropin-releasing hormone agonist.

It has been reported that the Gonadotropin-releasing hormone (GnRH) and its agonist leuprolide acetate (LA) can act as promoters of nerve regeneration. The aim of this study is to evaluate the effect of LA in a complete transection model. Sciatic nerve injury (SNI) was performed using a complete nerve transection and immediately repaired by epineural sutures. Rats were divided into three groups: SHAM, SNI treated with LA (SNI + LA) or saline solution (SNI + SS) for 5 weeks. Sciatic nerve regeneration was evaluated by kinematic gait analyzes, electrophysiological, morphological and biochemical tests. SNI + LA group had a functional recovery in kinematic gait, an increase in ankle angle value and a faster walking speed, compound muscle action potential amplitude, nerve conduction velocity (NCV). Furthermore, the number of myelinated axons and microtubule-associated protein 2 (MAP-2) expression were also higher compared to SS group. In conclusion, LA treatment improves of gait, walking speed, NCV, axons morphometry and MAP-2 expression in rats with sciatic nerve complete transection. These results suggest that LA can be a potential treatment for peripheral nerve injuries.