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Innate immune responses to innocuous Ags can either prevent or facilitate adaptive type 2 allergic inflammation, but the mechanisms are incompletely understood. We now demonstrate that macrophage UDP-specific type 6 purinergic (P2Y6) receptors selectively activate NFATC2, a member of the NFAT family, to drive an innate IL-12/IFN-γ axis that prevents type 2 allergic inflammation. UDP priming potentiated IL-12p40 production in bone marrow–derived macrophages (BMMs) stimulated by the house dust mite Dermatophagoides farinae (Df) in a P2Y6-dependent manner. Inhibitions of phospholipase C, calcium increase, and calcineurin eliminated UDP-potentiated Df-induced IL-12p40 production. UDP specifically induced nuclear translocation of NFATC2, but not NFATC1 and NFATC3, in BMMs in a P2Y6-dependent manner. UDP-potentiated IL-12p40 production by BMMs and Df-induced IL-12p40 gene expression by alveolar macrophages were abrogated in cells from Nfatc2 knockout mice. Pulmonary transplantation of wild-type but not Nfatc2 knockout macrophages increased Df-induced IL-12 production and IFN-γ expression in P2ry6 fl/fl/Cre/+ recipient mice. Finally, Nfatc2 knockout mice showed significantly increased indices of type 2 immunopathology in response to Df challenge, similar to P2ry6 fl/fl/Cre/+ mice. Thus, macrophage P2Y6 receptor signaling selectively utilizes NFATC2 to potentiate an innate IL-12/IFN-γ axis, a potential mechanism that protects against inappropriate type 2 immune responses.

A 71-year-old woman was admitted for the treatment of diffuse large B-cell lymphoma of the ileum. She had been taking lansoprazole but was switched to vonoprazan due to epigastric discomfort. Three weeks after starting vonoprazan intake, she had a convulsive seizure, and a blood test showed hypomagnesiemia. The cause of hypomagnesemia was considered to be malabsorption of magnesium from the intestinal tract associated with vonoprazan. After discontinuation of vonoprazan, the magnesium level quickly recovered, and the seizures did not relapse. It is important to consider the risk of hypomagnesemia in patients taking vonoprazan, even for a short period of time.

Instituto de Investigacion Marques de Valdecilla-IDIVAL (Santander, Spain), Official Doctoral Program in Biomedicine of the University of Granada, Plan Estatal de Investigaci´on Cient´ıfica y T´ecnica y de Innovaci´on 2013 2016, ISCIII-Subdirecci´on General de Evaluaci´on y Fomento de la Investigaci´on, Ministerio de Econom´ıa y Competitividad, Spain (Grants PI16/01642 and PI10/01096), Plan Propio de la Universidad de Granada, Spain 2014 (Grant PP2014.01)

Lysophosphatidic acid (LPA) plays a critical role in developing and maintaining chronic pain in various animal models. Previous studies have reported that cytosolic and calcium-independent phospholipase A2 (PLA2) is involved in the LPA receptor-mediated amplification of LPA production in the spinal dorsal horn (SDH) after nerve injury, while the involvement of secreted PLA2 (sPLA2) remains unclear. The present study revealed that only sPLA2 –III among 11 species of PLA2 showed a significant upregulation of gene expression in the SDH. Intraspinal injection of adeno-associated virus-miRNA targeting sPLA2-III prevented hyperalgesia and unique hypoalgesia in mice treated with partial sciatic nerve ligation. In addition, intrathecal treatment with antisense oligodeoxynucleotide or siRNA targeting sPLA2-III significantly reversed the established thermal hyperalgesia. In the high-throughput screening of sPLA2-III inhibitors from the chemical library, we identified two hit compounds. Through in vitro characterization of PLA2 inhibitor profiles and in vivo assessment of the anti-hyperalgesic effects of known PLA2 inhibitors as well as hit compounds, sPLA2-III was found to be a novel therapeutic target molecule for the treatment of Neuropathic pain.

The mammalian cerebral cortex is characterized by a 6-layer structure, and proper neuronal migration is critical for its formation. Cyclin-dependent kinase 5 (Cdk5) has been shown to be a critical kinase for neuronal migration. Several Cdk5 substrates have been suggested to be involved in ordered neuronal migration. However, in vivo loss-of-function studies on the function of Cdk5 phosphorylation substrates in neuronal migration in the developing cerebral cortex have not been reported. In this study, we demonstrated that Cdk5-mediated phosphorylation of collapsing mediator protein (CRMP) 2 is critical for neuronal migration in the developing cerebral cortex with redundant functions of CRMP1 and CRMP4. The cerebral cortices of triple-mutant CRMP1 knock-out (KO); CRMP2 knock-in (KI)/KI; and CRMP4 KO mice showed disturbed positioning of layers II–V neurons in the cerebral cortex. Further experiments using bromodeoxyuridine birthdate-labeling and in utero electroporation implicated radial migration defects in cortical neurons. Ectopic neurons were detected around the CA1 region and dentate gyrus in CRMP1 KO; CRMP2 KI/KI; and CRMP4 KO mice. These results suggest the importance of CRMP2 phosphorylation by Cdk5 and redundancy of CRMP1 and CRMP4 in proper neuronal migration in the developing cerebral cortex and hippocampus.

Protozoan parasites infect humans and many warm-blooded animals. Toxoplasma gondii, a major protozoan parasite, is commonly found in HIV-positive patients, organ transplant recipients and pregnant women, resulting in the severe health condition, Toxoplasmosis. Another major protozoan, Neospora caninum, which bears many similarities to Toxoplasma gondii, causes serious diseases in animals, as does Encephalomyelitis and Myositis-Polyradiculitis in dogs and cows, resulting in stillborn calves. All these exhibited similar nucleoside triphosphate hydrolases (NTPase). Neospora caninum has a NcNTPase, while Toxoplasma gondii has a TgNTPase-I. The enzymes are thought to play crucial roles in propagation and survival. In order to establish compounds and/or extracts preventing protozoan infection, we targeted these enzymes for drug discovery. The next step was to establish a novel, highly sensitive, and highly accurate assay by combining a conventional biochemical enzyme assay with a fluorescent assay to determine ADP content. We also validated that the novel assay fulfills the criteria to carry out high-throughput screening (HTS) in the two protozoan enzymes. We performed HTS, identified 19 compounds and six extracts from two synthetic compound libraries and an extract library derived from marine bacteria, respectively. In this study, a detailed explanation has been introduced on how to carry out HTS, including information about the preparation of reagents, devices, robot arm, etc.

Astrocytes are a type of glial cell that tile the CNS. They interact with multiple cell types, including neurons, glial cells and blood vessels, and are involved or implicated in brain disorders. Progress has been made in understanding astrocytes, but the field lacks detailed information concerning how they perform their multifarious functions, and how and when they influence the operations of the neural circuits with which they interact. One recognized bottleneck to progress has been the paucity of reliable tools with which to explore astrocytes within the adult vertebrate CNS in vivo. However, improved tools for molecular, genetic, morphological and physiological assessments have been developed recently or have been adapted from their original purposes to study neurons and are now being used to systematically document and interrogate astrocyte biology in vivo. These tools, their uses and limitations, and the insights that they afford are summarized in this Review. Much progress has been made in understanding astrocytes, but details on their functions and interactions remain difficult to determine. Yu, Nagai and Khakh give an overview of recent advances in the toolbox for molecular, genetic, morphological and physiological investigations into astrocytes.

BACKGROUND In the updated 2021 WHO classification, diffuse gliomas were strictly reclassified by molecular statuses. In glioblastoma (GBM), the prognostic significance of the resection has been shown, but the excision rate to be achieved in the new classification has not been defined. Moreover, the correlation between the extent of resection (EOR) and the prognosis is still controversial for other gliomas. METHODS IDH 1/2 mutations and TERT promoter mutations were analyzed by Sanger sequencing, 1p/19q co-deletion by microsatellite or MLPA, and EGFR amplification and CDKN2A deletions by MLPA. The correlation between the resection rate and prognosis of each tumor type in the 2021/2016 WHO classification was analyzed retrospectively. RESULTS According to the 2021 classification, 293 patients with GBM, IDH-wild type, 68 with astrocytoma, IDH-mutant (2/3/4 22/26/20), and 58 with oligodendroglioma, IDH-mutant and 1p/19q co-deleted were identified. Based on the 2016 classification, they were diagnosed as 314 GBM, 106 astrocytoma (Gd II/III 37/69), and 59 oligodendroglioma. For GBM, IDH-wild type (2021 classification), a prolonged OS benefit was observed with >25% removal (p=0.042), whereas, more than 20% of tumor removal for patients with GBM (2016 classification) resulted in OS prolongation. EOR was a significant favorable prognostic factor for grade II/III astrocytoma by the 2016 classification, but not for astrocytoma, IDH-mutant (grade 2/3) in the 2021 classification. When analyzed only in patients with astrocytoma, IDH-mutant by the 2021 classification, EOR was not significantly prognostic, suggesting that poorer prognosis of patients with unresectable IDH-wild type astrocytomas (2016 classification) might have a negative impact on the outcome. CONCLUSION There was a strong correlation between EOR and prognosis in patients with GBM, and >25% removal was considered significant according to the 2021 classification. For astrocytoma in the 2021 classification, EOR did not show a prognostic significance, but further validation including grading effect is warranted.

Primary dural low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a rare disease whose main treatment has been local surgery or radiotherapy. Until now, there have been no cases of dural MALT lymphoma treatment of a patient with several relapses or systemic disease. The present study included two patients with dural MALT lymphoma who had several relapses or systemic disease. Since local therapy was not enough to control the disease for these patients, they were treated with systemic chemotherapy. The patients were administered rituximab (375 mg/m(2)) and two days of bendamustine (90 mg/m(2)). Both patients recovered from their clinical symptoms immediately, and their tumors were reduced. During and after rituximab and bendamustine therapy, no central nervous system (CNS) metastasis or cerebrospinal fluid invasion of MALT were observed. The current approach using rituximab and bendamustine treatment was effective against dural MALT lymphoma and may prevent its invasion of the CNS.

Evans syndrome presents as concurrent autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Systemic lupus erythematosus (SLE) is the most frequent autoimmune disorder associated with Evans syndrome. We herein report a case of new-onset Evans syndrome associated with SLE after BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccination in a 53-year-old woman. Blood examination at diagnosis showed hemolytic anemia with a positive Coombs test and thrombocytopenia. Hypocomplementemia and the presence of lupus anticoagulant indicated a strong association with SLE. Prednisolone administration rapidly restored hemoglobin level and platelet count. This case suggests that mRNA COVID-19 vaccination may cause an autoimmune disorder. Physicians should be aware of this adverse reaction by mRNA COVID-19 vaccination and should consider the benefits and risks of vaccination for each recipient.

Summary Astrocytes respond to neurotransmitters and neuromodulators using G-protein-coupled receptors (GPCRs) to mediate physiological responses. Despite their importance, there has been no method to genetically, specifically, and effectively attenuate astrocyte Gq GPCR pathways to explore consequences of this prevalent signaling mechanism in vivo. We report a 122-residue inhibitory peptide from β-adrenergic receptor kinase 1 (iβARK; and inactive D110A control) to attenuate astrocyte Gq GPCR signaling. iβARK significantly attenuated Gq GPCR Ca2+ signaling in brain slices and, in vivo, altered behavioral responses, spared other GPCR responses, and did not alter astrocyte spontaneous Ca2+ signals, morphology, electrophysiological properties, or gene expression in the striatum. Furthermore, brain-wide attenuation of astrocyte Gq GPCR signaling with iβARK using PHP.eB adeno-associated viruses (AAVs), when combined with c-Fos mapping, suggested nuclei-specific contributions to behavioral adaptation and spatial memory. iβARK extends the toolkit needed to explore functions of astrocyte Gq GPCR signaling within neural circuits in vivo.

Besides neurons, the other half of central nerve system (CNS) cells are glia. Astrocytes, the most abundant glia, were first found together with neurons around 150 years ago, and have long been considered as merely supportive cells. Recent studies suggest that, far from being a "glue", they are specialized contributors to brain physiology and disease. Astrocytes contact neurons and synapses via their myriad fine processes. They exert versatile homeostatic and neuro-modulatory functions to regulate CNS activity. As the term neuroscience suggests, brain research in the twentieth century was dominated by neuronal studies. In contrast, astrocytes, without which neurons cannot properly function, have been understudied partially due to a lack of tools. Fortunately, recent genetics, optics and protein engineering now provide the tools needed for astrocytes to tackle an exciting area of integrative brain cell biology. This paper presents a summary of the improved tools, the insights that they delivere, and the potential directions of future developments.

Adenosine 5′ triphosphate (ATP) is a universal intracellular energy source and an evolutionarily ancient, ubiquitous extracellular signal in diverse species. Here, we report the generation and characterization of single-wavelength genetically encoded fluorescent sensors (iATPSnFRs) for imaging extracellular and cytosolic ATP from insertion of circularly permuted superfolder GFP into the epsilon subunit of F0F1-ATPase from Bacillus PS3. On the cell surface and within the cytosol, iATPSnFR1.0 responds to relevant ATP concentrations (30 μM to 3 mM) with fast increases in fluorescence. iATPSnFRs can be genetically targeted to specific cell types and sub-cellular compartments, imaged with standard light microscopes, do not respond to other nucleotides and nucleosides, and when fused with a red fluorescent protein function as ratiometric indicators. After careful consideration of their modest pH sensitivity, iATPSnFRs represent promising reagents for imaging ATP in the extracellular space and within cells during a variety of settings, and for further application-specific refinements., ATP has essential roles in cell signalling and energy homeostasis and biosensors to detect it have many potential applications. Here, the authors develop a new ATP sensor that can be targeted to the membrane or cytosol.

Lysophosphatidic acid (LPA) plays a critical role in developing and maintaining chronic pain in various animal models. Previous studies have reported that cytosolic and calcium-independent phospholipase A

Repressor element-1 (RE-1) or neural restrictive silencer element (NRSE) bound with a zinc finger transcription repressor, RE-1 silencing transcription factor (REST, also known as neural restrictive silencer factor, NRSF) has been identified as a fundamental repressor element in many genes, including neuronal genes. Genes regulated by REST/NRSF regulate multifaceted neuronal phenotypes, and their defects in the machinery cause neuropathies, disorders of neuron activity), autism and so on. In REST repressions, the N-terminal repressor domain recruits Sin3B via its paired amphipathic helix 1 (PAH1) domain, which plays an important role as a scaffold for histone deacetylase 1 and 2. This machinery has a critical role in maintaining neuronal robustness. In this study, in order to establish protein–protein interaction assays mimicking a binding surface between Sin3B and REST, we selected important amino acids from structural information of the PAH1/REST complex and then tried to reconstitute it using recombinant short peptides derived from PAH1/REST. Initially, we validated whether biotinylated REST interacts with glutathione S-transferase (GST)-tagged PAH1 and whether another PAH1 peptide (PAH1-FLAG) competitively binds with biotinylated REST using surface plasmon resonance (SPR). We observed a direct interaction and competitive binding of two PAH1 peptides. Secondly, in order to establish a high-throughput and high-dynamic-range assay, we utilized an easily performed novel time-resolved fluorescence energy transfer (TR-FRET) assay, and closely monitored this interaction. Finally, we succeeded in establishing a novel high-quality TR-FRET assay and a novel interaction assay based on SPR.

Astrocytes represent a large and diverse population of morphologically complex cells that exist throughout nervous systems of multiple species. Progress over the last two decades has shown that astrocytes mediate developmental, physiological, and pathological processes. However, a longstanding open question concerns how astrocytes regulate neural circuits in ways that are behaviorally consequential. In these regards, we summarize recent studies from Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, and Mus musculus. The data reveal diverse astrocyte mechanisms operating on seconds or much longer time scales within neural circuits and shaping multiple behavioral outputs. We also refer to human diseases that have a known primary astrocytic basis. We suggest that including astrocytes in mechanistic, theoretical, and computational studies of neural circuits provides new perspectives to understand behavior, its regulation, and its disease-related manifestations.

Non-Orthogonal Multiple Access (NOMA) is expected to enhance spectrum utilization in 5G and beyond 5G mobile communication systems. Since NOMA multiplexes signals for multiple users into one radio resource, there is an issue that the influence of nonlinear distortion caused by radio frequency circuits becomes more severe. In this paper, we propose to mitigate the effects of nonlinear distortion by a blind nonlinear compensation technique in the receiver side. The improvement effect is evaluated by Error Vector Magnitude (EVM) of the received signal. From the computer simulation results, it is confirmed that the proposed method can effectively suppress the deterioration of downlink NOMA received signal that is affected by nonlinear distortion. As a result, it is possible to apply high-level modulation such as 256QAM in NOMA under such environments.

BACKGROUND: The 3 cysteinyl leukotrienes (cysLTs), leukotriene (LT) C(4) (LTC(4)), LTD(4), and LTE(4), have different biologic half-lives, cellular targets, and receptor specificities. CysLT(2)R binds LTC(4) and LTD(4) in vitro with similar affinities, but it displays a marked selectivity for LTC(4) in vivo. LTC(4), but not LTD(4), strongly potentiates allergen-induced pulmonary eosinophilia in mice through a CysLT(2)R-mediated, platelet-and IL-33–dependent pathway. OBJECTIVE: We sought to determine whether LTD(4) functionally antagonizes LTC(4) signaling at CysLT(2)R. METHODS: We used 2 different in vivo models of CysLT(2)R-dependent immunopathology, as well as ex vivo activation of mouse and human platelets. RESULTS: LTC(4)-induced CD62P expression; HMGB1 release; and secretions of thromboxane A(2), CXCL7, and IL-33 by mouse platelets were all were blocked by a selective CysLT(2)R antagonist and inhibited by LTD(4). These effects did not depend on CysLT(1)R. Inhaled LTD(4) blocked LTC(4)-mediated potentiation of ovalbumin-induced eosinophilic inflammation; recruitment of platelet-adherent eosinophils; and increases in IL-33, IL-4, IL-5, and IL-13 levels in lung tissue. In contrast, the effect of administration of LTE(4), the preferred ligand for CysLT(3)R, was additive with LTC(4). The administration of LTD(4) to Ptges(−/−) mice, which display enhanced LTC(4) synthesis similar to that in aspirin-exacerbated respiratory disease, completely blocked the physiologic response to subsequent lysine-aspirin inhalation challenges, as well as increases in levels of IL-33, type 2 cytokines, and biochemical markers of mast cell and platelet activation. CONCLUSION: The conversion of LTC(4) to LTD(4) may limit the duration and extent of potentially deleterious signaling through CysLT(2)R, and it may contribute to the therapeutic properties of desensitization to aspirin in aspirin-exacerbated respiratory disease.

Background: Transcriptional regulation is a very important and pivotal function in myriad biological responses. Thus, methods to determine transcriptional activity are required in not only basic medical research but also in drug discovery. We established novel reporter constructs using human secreted embryonic alkaline phosphatase (SEAP) and Epstein-Barr virus nuclear antigen (EBNA) 1, which can maintain constructs synchronized to host cell replication. Methods: We established nuclear factor-kappa B (NFkB) or interferon regulatory factor (IRF) driven SEAP expression constructs and then, introduced them into culture cells. Results: The cells maintain reporter constructs for a long period in the culture and produce SEAP into culture supernatant in response to each specific ligand such as lipopolysaccharide (LPS) and inter-feron-beta. Measuring SEAP with chemiluminescence makes it possible to get high standard dynamic range applying to high-throughput screening in drug discovery in both 96 and 384 well format. We can also use it to determine transcriptional activity in the cells transfected with expression plasmid or treated with various toll-like receptor (TLR) ligands in a concentration-dependent manner and time-dependent manner. Finally, we demonstrated drug screening using a number of natural products library. Conclusion: We for the first time established the two novel reporter cells and validated their quality and accuracy enough to carry out drug screening., Current Pharmaceutical Biotechnology, 19(3), pp.224-231; 2018

Axonal degeneration occurs in patients with various neurological diseases and traumatic nerve injuries, and Wallerian degeneration is a phenomenon in the prototypical axonal degradation that is observed after injury. Collapsin response mediator protein 2 (CRMP2) is phosphorylated by glycogen synthase kinase 3β (GSK3β), and it is involved in Wallerian degeneration after optic nerve injury. We previously developed a CRMP2 knock-in (CRMP2 KI) mouse line, in which CRMP2 phosphorylation by GSK3β is inhibited; however, Wallerian degeneration in CRMP2 KI mice has not yet been examined. In this study, we examined whether Wallerian degeneration of the optic nerve is suppressed in CRMP2 KI mice. Using one eye removal model, we compared Wallerian degeneration of the optic nerve based on histological and biochemical analyses. Our experimental results indicated that the genetic inhibition of CRMP2 phosphorylation delays Wallerian degeneration after optic nerve injury.

Background The 3 cysteinyl leukotrienes (cysLTs), leukotriene (LT) C4 (LTC4), LTD4, and LTE4, have different biologic half-lives, cellular targets, and receptor specificities. CysLT2R binds LTC4 and LTD4 in vitro with similar affinities, but it displays a marked selectivity for LTC4 in vivo. LTC4, but not LTD4, strongly potentiates allergen-induced pulmonary eosinophilia in mice through a CysLT2R-mediated, platelet- and IL-33–dependent pathway. Objective We sought to determine whether LTD4 functionally antagonizes LTC4 signaling at CysLT2R. Methods We used 2 different in vivo models of CysLT2R-dependent immunopathology, as well as ex vivo activation of mouse and human platelets. Results LTC4-induced CD62P expression; HMGB1 release; and secretions of thromboxane A2, CXCL7, and IL-33 by mouse platelets were all were blocked by a selective CysLT2R antagonist and inhibited by LTD4. These effects did not depend on CysLT1R. Inhaled LTD4 blocked LTC4-mediated potentiation of ovalbumin-induced eosinophilic inflammation; recruitment of platelet-adherent eosinophils; and increases in IL-33, IL-4, IL-5, and IL-13 levels in lung tissue. In contrast, the effect of administration of LTE4, the preferred ligand for CysLT3R, was additive with LTC4. The administration of LTD4 to Ptges–/– mice, which display enhanced LTC4 synthesis similar to that in aspirin-exacerbated respiratory disease, completely blocked the physiologic response to subsequent lysine-aspirin inhalation challenges, as well as increases in levels of IL-33, type 2 cytokines, and biochemical markers of mast cell and platelet activation. Conclusion The conversion of LTC4 to LTD4 may limit the duration and extent of potentially deleterious signaling through CysLT2R, and it may contribute to the therapeutic properties of desensitization to aspirin in aspirin-exacerbated respiratory disease.

It is essential to continue the search for novel antimalarial drugs due to the current spread of resistance against artemisinin by Plasmodium falciparum parasites. In this study, we developed in silico models to predict hemozoin inhibitors as a potential first-step screening for novel antimalarials. An in vitro colorimetric highthroughput screening assay of hemozoin formation was used to identify hemozoin inhibitors from 9,600 structurally diverse compounds. The physicochemical properties of positive hits and randomly selected compounds were extracted from the ChemSpider database; they were used for developing prediction models to predict hemozoin inhibitors using two different approaches, i.e., traditional multivariate logistic regression and Bayesian model averaging. Our results showed that a total of 224 positive-hit compounds exhibited the ability to inhibit hemozoin formation, with 50% inhibitory concentrations (IC50s) ranging from 3.1 μM to 199.5 μM. The best model according to traditional multivariate logistic regression included the three variables octanol-water partition coefficient, number of hydrogen bond donors, and number of atoms of hydrogen, while the best model according to Bayesian model averaging included the three variables octanol-water partition coefficient, number of hydrogen bond donors, and index of refraction. Both models had a good discriminatory power, with area under the curve values of 0.736 and 0.781 for the traditional multivariate model and Bayesian model averaging, respectively. In conclusion, the prediction models can be a new, useful, and cost-effective approach for the first screen of hemozoin inhibition-based antimalarial drug discovery., Antimicrobial Agents and Chemotherapy, 61, 2, e01607-16; 2017

The mammalian central nervous system (CNS) has limited regenerative ability after injury, largely due to scar formation and axonal growth inhibitors. Experimental suppression of neuroinflammation encourages recovery from spinal cord injury (SCI), yet practical means for pharmacologically treating SCI have remained elusive. Lanthionine ketimine (LK) is a natural brain sulfur amino acid metabolite with demonstrated anti-neuroinflammatory and neurotrophic activities. LK and its synthetic brain-penetrating ethyl ester (LKE) promote growth factor-dependent neurite extension in cultured cell and suppress microglial activation in animal models of neurodegeneration. Thus far however, LKE has not been explored as a potential therapy for SCI. The present study investigated the hypothesis that systemic LKE could improve motor functional recovery after SCI in a mouse model. Intraperitoneal administration of LKE (100 mg/kg/d) after near-complete transect of spinal cord at the T7 level significantly improved motor function over a 4-week time course. Vehicle-treated mice, in contrast, demonstrated negligible functional recovery. In terms of histology, LKE treatment reduced pro-neuroinflammatory microglia/macrophage activation evidenced by quantitative Iba1 labeling and shifted the microglial phenotype toward a more neurotrophic M2 character evidenced by changes in the M2 marker arginase-1. This was correlated with less dense scar formation and more extensive axonal regrowth across the transection site demonstrated by 5-hydroxytryptamine (5HT) immunolabeling of raphespinal tract axons. These data provide evidence that LKE or similar compounds have potential therapeutic value for recovery after certain forms of SCI.