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Alexander disease is a leukodystrophy caused by dominant missense mutations in the gene encoding the glial fibrillary acidic protein. Individuals with this disorder often present with a typical neuroradiologic pattern including white matter abnormalities with brainstem involvement, selective contrast enhancement, and structural changes to the basal ganglia/thalamus. In rare cases, focal lesions have been seen and cause concern for primary malignancies. Here the authors present an infant initially diagnosed with a chiasmatic astrocytoma that was later identified as having glial fibrillary acidic protein mutation-confirmed Alexander disease. Pathologic and radiologic considerations that were helpful in arriving at the correct diagnosis are discussed. [ABSTRACT FROM AUTHOR]

Objective To demonstrate an association between magnetic resonance imaging ( MRI) findings and pathologic characteristics in children who had surgery for medically refractory epilepsy due to focal cortical dysplasia ( FCD). Methods We retrospectively studied 110 children who had epilepsy surgery. Twenty-seven patients with FCD were included. Thirteen had temporal lobe epilepsy ( TLE) and 14 had extra-temporal lobe epilepsy ( ETLE). Three patients had associated mesial temporal sclerosis. Preoperative 3T MRIs interleaved with nine controls were blindly re-reviewed and categorized according to signal alteration. Pathologic specimens were classified according to the 2011 International League Against Epilepsy ( ILAE) classification and compared to MRI studies. Results Rates of pathology subtypes differed between TLE and ETLE (χ2(3) = 8.57, p = 0.04). FCD type I was more frequent in TLE, whereas FCD type II was more frequent in ETLE. In the TLE group, nine patients had temporal tip abnormalities. They all exhibited gray-white matter blurring with decreased myelination and white matter hyperintense signal. Blurring involved the whole temporal tip, not just the area of dysplasia. These patients were less likely to demonstrate cortical thickening compared to those without temporal tip findings (χ2(1) = 9.55, p = 0.002). Three of them had FCD Ib, three had FCD IIa, two had FCD IIIa, and one had FCD IIb; MRI features could not entirely distinguish between FCD subtypes. TLE patients showed more pronounced findings than ETLE on MRI (χ2(1) = 11.95, p = 0.003, odds ratio [ OR] 18.00). In all cases of FCD, isolated blurring was more likely to be associated with FCD II, whereas blurring with decreased myelination was seen with FCD I (χ2(6) = 13.07, p = 0.042). Significance Our study described associations between MRI characteristics and pathology in children with FCD and offered a detailed analysis of temporal lobe tip abnormalities and FCD subtypes in children with TLE. These findings may contribute to the presurgical evaluation of patients with refractory epilepsy. [ABSTRACT FROM AUTHOR]

Highlights: [•] Crystallographic orientation of Cu6Sn5 was revealed by utilizing the EBSD analysis. [•] The growth behavior of interfacial IMC on Ni(P) and Cu sides were distinct. [•] The random texture of (Cu,Ni,Pd)6Sn5 on Ni(P) side might hinder the crack propagation. [•] The concentrated texture of IMC could lower the possibility for cracking. [•] (Cu,Ni,Pd)6Sn5 on both sides of assembled joint exhibited the desired grain texture. [Copyright &y& Elsevier]

Abstract: The tunable growth of In-doped Ga2O3 (Ga2O3:In) and Ga-doped In2O3 (In2O3:Ga) nanowires (NWs) on Au-coated Si substrates was achieved by modulating the amount of water vapor in flowing Ar at 700–750°C via carbothermal reduction of Ga2O3/In2O3 powders with a fixed weight ratio. In Ar, only the Ga2O3:In NWs were grown, while in wet Ar the In2O3:Ga NWs were synthesized instead. The Ga concentration in In2O3 NWs decreased with the increment of water vapor in flowing Ar. The growth of both Ga2O3:In and In2O3:Ga NWs followed the vapor–liquid–solid process. The In and Ga doping induced a redshift and a blueshift in the optical bandgaps of Ga2O3 NWs and In2O3 NWs, respectively. The growth mechanisms and optical properties of Ga2O3:In and In2O3:Ga NWs were discussed. [Copyright &y& Elsevier]

Abstract: In the Sn–3.0Ag–0.5 Cu/Ni (wt%; SAC305/Ni) solder joint, the (Cu,Ni)6Sn5 spalling was suppressed by altering the microstructure of Ni films. Ni films with intertwined and straight grain boundaries (GBs) were fabricated by the diverse target powers of the direct current magnetron sputter. The intertwined GB and the straight GB of Ni films determined the degree of the (Cu,Ni)6Sn5 spalling. Ni films with straight GB accelerated the (Cu,Ni)6Sn5 spalling due to the fast diffusion path of Ni and Cu in straight GB of Ni films. In contrast, the winding grain structure of Ni film, called intertwined GB-Ni film, can suppress the interdiffusion of Cu and Ni. Thus, the (Cu,Ni)6Sn5 spalling was successfully retarded by the Ni structure with intertwined GB. [Copyright &y& Elsevier]

Children diagnosed with brain tumors have the lowest overall survival of all pediatric cancers. Recent molecular studies have resulted in the discovery of recurrent driver mutations in many pediatric brain tumors. However, despite these molecular advances, the clinical outcomes of high grade tumors, including H3K27M diffuse midline glioma (H3K27M DMG), remain poor. To address the paucity of tissue for biological studies, we have established a comprehensive protocol for the coordination and processing of donated specimens at postmortem. Since 2010, 60 postmortem pediatric brain tumor donations from 26 institutions were coordinated and collected. Patient derived xenograft models and cell cultures were successfully created (76% and 44% of attempts respectively), irrespective of postmortem processing time. Histological analysis of mid-sagittal whole brain sections revealed evidence of treatment response, immune cell infiltration and the migratory path of infiltrating H3K27M DMG cells into other midline structures and cerebral lobes. Sequencing of primary and disseminated tumors confirmed the presence of oncogenic driver mutations and their obligate partners. Our findings highlight the importance of postmortem tissue donations as an invaluable resource to accelerate research, potentially leading to improved outcomes for children with aggressive brain tumors. [ABSTRACT FROM AUTHOR]

Type IV sacrococcygeal teratoma with intraspinal involvement is rare and to our knowledge has not been reported previously in the literature. The authors present the case of a 2-month-old infant with a type IV sacrococcygeal teratoma diagnosed on prenatal ultrasound. Postnatal MRI revealed intraspinal extension through an enlarged sacral neuroforamina on the right side. On surgical exploration, the authors discovered a dorsal cystic tumor involving the sacral spine that extended through an enlarged S4 foramen to a large presacral component. The tumor was successfully removed to achieve a complete en bloc surgical resection. The authors review the epidemiology, pathophysiology, and treatment of sacrococcygeal teratomas with intraspinal extension. [ABSTRACT FROM AUTHOR]

Purpose/objectives: Radiation-induced erectile-dysfunction (RiED) is one of the most common side effects of radiation therapy (RT) and significantly reduces the quality of life (QoL) of cancer patients. Approximately 50% of prostate cancer patients experience RiED within 3 to 5 years after completion of RT. A series of vascular, muscular, and neurogenic injuries after prostate RT lead to RiED; however, the precise role of RT-induced neurogenic injury in RiED has not been fully established. The cavernous nerves (CN) are postganglionic parasympathetic nerves located beside the prostate gland that assist in penile erection. This study was designed to investigate the role of CN injury, tissue damage, and altered signaling pathways in an RiED rat model.Methods and Materials: Male rats were exposed to a single dose of 25 Gy prostate-confined RT. Erectile function was evaluated by intracavernous pressure (ICP) measurements conducted both 9 and 14 weeks after RT. Neuronal injury was evaluated in the CN using quantitative polymerase chain reaction, conduction studies, transmission electron microscopy, and immunoblotting. Masson trichrome staining was performed to elucidate fibrosis level in penile tissues.Results: There were significant alterations in the ICP (P<.0001) of RT rats versus non-RT rats. TEM analysis showed decreased myelination, increased microvascular damage, and progressive axonal atrophy of the CN fibers after RT. Electrophysiologic analysis showed significant impairment of the CN conduction velocity after RT. RT also significantly increased RhoA/Rho-associated protein kinase 1 (ROCK1) mRNA and protein expression. In addition, penile tissue showed increased apoptosis and fibrosis 14 weeks after RT.Conclusions: RT-induced CN injury may contribute to RiED; this is therefore a rationale for developing novel therapeutic strategies to mitigate CN and tissue damage. Moreover, further investigation of the RhoA/ROCK pathway's role in mitigating RiED is necessary. [ABSTRACT FROM AUTHOR]

Objective: The detection of neoplastic cells in cerebral spinal fluid (CSF) is pivotal for the management of patients with central nervous system (CNS) tumours. This article delves into the CSF cytological characteristics of common CNS neoplasms, aligning with the 2021 World Health Organization (WHO) classification of CNS tumours., Methods: A retrospective review of CSF specimens positive for primary CNS neoplasms was performed at three tertiary medical centres. Only cases that had histopathologic confirmation and/or molecular workup were included., Results: Common primary CNS neoplasms seen in CSF cytology specimens include medulloblastoma, (non-WNT/non-SHH as well as SHH-activated and TP53 mutant), pineoblastoma, atypical teratoid/rhabdoid tumour (AT/RT), IDH-wildtype glioblastoma, and primary diffuse large B-cell lymphoma of the CNS. Ependymomas and germinomas can also have CSF involvement but are less common. Although the typical histologic architecture of these tumours may not be preserved in the CSF, unique cytomorphologic features such as nuclear moulding, nuclear pleomorphism, rhabdoid cells, prominent nucleoli and rosette formation can still be appreciated., Conclusion: Adopting the updated terminology and correlating cytologic observations with molecular findings will streamline the diagnostic process, reducing the complexities and ambiguities pathologists often encounter when analysing CSF specimens for potential primary CNS neoplasms., (© 2023 John Wiley & Sons Ltd.)

Context.—: Spontaneous (nontraumatic) subdural hematomas have been reported yet have not been well studied., Objective.—: To identify the neuropathologic features of acute spontaneous SDHs (ASSDHs) and their associated medical conditions., Design.—: A retrospective study of 235 autopsy cases of SDH was conducted. Review of demographics, underlying medical conditions, and coagulation profile as well as gross and histopathologic examination of the brain and other organs were performed., Results.—: Among the 32 cases of ASSDH, 5 cases (15.6%) had severe hemorrhage and 4 (12.5%) demonstrated brain herniation. Twenty-two cases (68.8%) had concurrent but nonconnecting subarachnoid hemorrhage or intraparenchymal hemorrhage. The most common underlying medical condition was thrombocytopenia (n = 21; 65.6%), followed by immunosuppression (n = 15; 46.9), bloodstream infections or sepsis (n = 12; 37.5%), hypertension (n = 13; 40.6%), and coronary artery disease (n = 12; 37.5%). Many patients with thrombocytopenia or immunosuppression had underlying malignancies, with leukemia being the most common type (n = 11; 34.4%). The use of circulatory devices or hemodialysis was noted in a significant portion of ASSDH cases. In terms of coagulation factors, most of our ASSDH patients had normal prothrombin time and activated partial thromboplastin time, but abnormal platelet count and D-dimer levels., Conclusions.—: ASSDHs can be severe and are often associated with subarachnoid hemorrhage and/or intraparenchymal hemorrhage. The causes of ASSDH are limited to certain underlying medical conditions that ultimately lead to bleeding tendency. Autopsies are helpful in determining the etiology. Given their association with abnormal platelet count, correcting platelet deficiencies is a potential preventive measure for ASSDHs., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

The phosphate modification of drugs is a common chemical strategy to increase solubility and allow for parenteral administration. Unfortunately, phosphate modifications often elicit treatment- or dose-limiting pruritus through an unknown mechanism. Using unbiased high-throughput drug screens, we identified the Mas-related G protein-coupled receptor X4 (MRGPRX4), a primate-specific, sensory neuron receptor previously implicated in itch, as a potential target for phosphate-modified compounds. Using both G q -mediated calcium mobilization and G protein-independent GPCR assays, we found that phosphate-modified compounds potently activate MRGPRX4. Furthermore, a humanized mouse model expressing MRGPRX4 in sensory neurons exhibited robust phosphomonoester prodrug-evoked itch. To characterize and confirm this interaction, we further determined the structure of MRGPRX4 in complex with a phosphate-modified drug through single-particle cryo-electron microscopy (cryo-EM) and identified critical amino acid residues responsible for the binding of the phosphate group. Together, these findings explain how phosphorylated drugs can elicit treatment-limiting itch and identify MRGPRX4 as a potential therapeutic target to suppress itch and to guide future drug design.

Olfactory dysfunction is one of the most common symptoms of COVID-19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has significantly decreased with the emergence of the Omicron variant, which has since become the dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID-19-associated olfactory dysfunction an ongoing health concern. The proposed pathogenic mechanisms of COVID-19-associated olfactory dysfunction are complex and likely multifactorial. While evidence suggests that infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, alterations in other components of the olfactory system (e.g., olfactory receptor neuron dysfunction, olfactory bulb injury and alterations in the olfactory cortex) may lead to persistent, long-term olfactory dysfunction. This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations and current understanding of the pathogenic mechanisms of COVID-19-associated olfactory dysfunction., (© 2024 British Neuropathological Society.)

Diabetic neuropathy is a debilitating disorder characterized by spontaneous and mechanical allodynia. The role of skin mechanoreceptors in the development of mechanical allodynia is unclear. We discovered that mice with diabetic neuropathy had decreased sirtuin 1 (SIRT1) deacetylase activity in foot skin, leading to reduced expression of brain-derived neurotrophic factor (BDNF) and subsequent loss of innervation in Meissner corpuscles, a mechanoreceptor expressing the BDNF receptor TrkB. When SIRT1 was depleted from skin, the mechanical allodynia worsened in diabetic neuropathy mice, likely due to retrograde degeneration of the Meissner-corpuscle innervating Aβ axons and aberrant formation of Meissner corpuscles which may have increased the mechanosensitivity. The same phenomenon was also noted in skin-keratinocyte specific BDNF knockout mice. Furthermore, overexpression of SIRT1 in skin induced Meissner corpuscle reinnervation and regeneration, resulting in significant improvement of diabetic mechanical allodynia. Overall, the findings suggested that skin-derived SIRT1 and BDNF function in the same pathway in skin sensory apparatus regeneration and highlighted the potential of developing topical SIRT1-activating compounds as a novel treatment for diabetic mechanical allodynia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This research models and forecasts bounded ordinal time series data that can appear in various contexts, such as air quality index (AQI) levels, economic situations, and credit ratings. This class of time series data is characterized by being bounded and exhibiting a concentration of large probabilities on a few categories, such as states 0 and 1. We propose using Bayesian methods for modeling and forecasting in zero-one-inflated bounded Poisson autoregressive (ZOBPAR) models, which are specifically designed to capture the dynamic changes in such ordinal time series data. We innovatively extend models to incorporate exogenous variables, marking a new direction in Bayesian inferences and forecasting. Simulation studies demonstrate that the proposed methods accurately estimate all unknown parameters, and the posterior means of parameter estimates are robustly close to the actual values as the sample size increases. In the empirical study we investigate three datasets of daily AQI levels from three stations in Taiwan and consider five competing models for the real examples. The results exhibit that the proposed method reasonably predicts the AQI levels in the testing period, especially for the Miaoli station.

Objective: To test the hypothesis that brain injury is more common and varied in patients receiving extracorporeal membrane oxygenation (ECMO) than radiographically observed, we described neuropathology findings of ECMO decedents and associated clinical factors from 3 institutions., Methods: We conducted a retrospective multicenter observational study of brain autopsies from adult ECMO recipients. Pathology findings were examined for correlation with demographics, clinical data, ECMO characteristics, and outcomes., Results: Forty-three decedents (n = 13 female, median age 47 years) received autopsies after undergoing ECMO for acute respiratory distress syndrome (n = 14), cardiogenic shock (n = 14), and cardiac arrest (n = 15). Median duration of ECMO was 140 hours, most decedents (n = 40) received anticoagulants; 60% (n = 26) underwent venoarterial ECMO, and 40% (n = 17) underwent venovenous ECMO. Neuropathology was found in 35 decedents (81%), including microhemorrhages (37%), macrohemorrhages (35%), infarctions (47%), and hypoxic-ischemic brain injury (n = 17, 40%). Most pathology occurred in frontal neocortices (n = 43 occurrences), basal ganglia (n = 33), and cerebellum (n = 26). Decedents with hemorrhage were older (median age 57 vs 38 years, p = 0.01); those with hypoxic brain injury had higher Sequential Organ Failure Assessment scores (8.0 vs 2.0, p = 0.04); and those with infarction had lower peak Paco 2 (53 vs 61 mm Hg, p = 0.04). Six of 9 patients with normal neuroimaging results were found to have pathology on autopsy. The majority underwent withdrawal of life-sustaining therapy (n = 32, 74%), and 2 of 8 patients with normal brain autopsy underwent withdrawal of life-sustaining therapy for suspected neurologic injury., Conclusion: Neuropathological findings after ECMO are common, varied, and associated with various clinical factors. Further study on underlying mechanisms is warranted and may guide ECMO management., (© 2021 American Academy of Neurology.)

Recent characterization of spatiotemporal genomic architecture of IDH-wild-type multifocal glioblastomas (M-GBMs) suggests a clinically unobserved common-ancestor (CA) with a less aggressive phenotype, generating highly genetically divergent malignant gliomas/GBMs in distant brain regions. Using serial MRI/3D-reconstruction, whole-genome sequencing and spectral karyotyping-based single-cell phylogenetic tree building, we show two distinct types of tumor evolution in p53-mutant driven mouse models. Malignant gliomas/GBMs grow as a single mass (Type 1) and multifocal masses (Type 2), respectively, despite both exhibiting loss of Pten/chromosome 19 (chr19) and PI3K/Akt activation with sub-tetraploid/4N genomes. Analysis of early biopsied and multi-segment tumor tissues reveals no evidence of less proliferative diploid/2N lesions in Type 1 tumors. Strikingly, CA-derived relatively quiescent tumor precursors with ancestral diploid/2N genomes and normal Pten/chr19 are observed in the subventricular zone (SVZ), but are distantly segregated from multi focal Type 2 tumors. Importantly, PI3K/Akt inhibition by Rictor/mTORC2 deletion blocks distant dispersal, restricting glioma growth in the SVZ.

Innocuous mechanical stimuli acting on the skin are detected by sensory neurons, known as low-threshold mechanoreceptors (LTMRs). LTMRs are classified based on their response properties, action potential conduction velocity, rate of adaptation to static indentation of the skin, and terminal anatomy. Here, we report organizational properties of the cutaneous and central axonal projections of the five principal hairy skin LTMR subtypes. We find that axons of neurons within a particular LTMR class are largely nonoverlapping with respect to their cutaneous end organs (e.g., hair follicles), with Aβ rapidly adapting-LTMRs being the sole exception. Individual neurons of each LTMR class are mostly nonoverlapping with respect to their associated hair follicles, with the notable exception of C-LTMRs, which exhibit multiple branches that redundantly innervate individual hair follicles. In the spinal cord, LTMR central projections exhibit rostrocaudal elongation and mediolateral compression, compared with their cutaneous innervation patterns, and these central projections also exhibit a fine degree of homotypic topographic adjacency. These findings thus reveal homotypic tiling of LTMR subtype axonal projections in hairy skin and a remarkable degree of spatial precision of spinal cord axonal termination patterns, suggesting a somatotopically precise tactile encoding capability of the mechanosensory dorsal horn., Competing Interests: The authors declare no conflict of interest.

Survival of human peripheral nervous system neurons and associated distal axons is highly dependent on energy. Diabetes invokes a maladaptation in glucose and lipid energy metabolism in adult sensory neurons, axons and Schwann cells. Mitochondrial (Mt) dysfunction has been implicated as an etiological factor in failure of energy homeostasis that results in a low intrinsic aerobic capacity within the neuron. Over time, this energy failure can lead to neuronal and axonal degeneration and results in increased oxidative injury in the neuron and axon. One of the key pathways that is impaired in diabetic peripheral neuropathy (DPN) is the energy sensing pathway comprising the nicotinamide-adenine dinucleotide (NAD + )-dependent Sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-γ coactivator α (PGC-1α)/Mt transcription factor A (TFAM or mtTFA) signaling pathway. Knockout of PGC-1α exacerbates DPN, whereas overexpression of human TFAM is protective. LY379268, a selective metabolomic glutamate receptor 2/3 (mGluR2/3) receptor agonist, also upregulates the SIRT1/PGC-1α/TFAM signaling pathway and prevents DPN through glutamate recycling in Schwann/satellite glial (SG) cells and by improving dorsal root ganglion (DRG) neuronal Mt function. Furthermore, administration of nicotinamide riboside (NR), a precursor of NAD + , prevents and reverses DPN, in part by increasing NAD + levels and SIRT1 activity. In summary, we review the role of NAD + , mitochondria and the SIRT1-PGC-1α-TFAM pathway both from the perspective of pathogenesis and therapy in DPN., (© 2019 Elsevier Inc. All rights reserved.)

For the past decade, it has been recognized that pediatric low-grade gliomas (LGGs) and glial-neuronal tumors carry distinct molecular alterations with resultant aberrant intracellular signaling in the Ras-mitogen-activated protein kinase pathway. The conclusions and recommendations of a consensus conference of how best to integrate the growing body of molecular genetic information into tumor classifications and, more importantly, for future treatment of pediatric LGGs are summarized here. There is uniform agreement that molecular characterization must be incorporated into classification and is increasingly critical for appropriate management. Molecular-targeted therapies should be integrated expeditiously, but also carefully into the management of these tumors and success measured not only by radiographic responses or stability, but also by functional outcomes. These trials need to be carried out with the caveat that the long-term impact of molecularly targeted therapy on the developing nervous system, especially with long duration treatment, is essentially unknown., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Allergic airway disorder is characterized by an increase in the level of reactive oxygen species (ROS). The induction of inflammation and hyperresponsiveness by an allergen was ameliorated by antioxidants in vivo. This study investigated the protective effects and underlying mechanism of diallyl sulfide (DAS) on ovalbumin (OVA)-induced allergic asthma of BALB/c mice. The animals were intraperitoneally sensitized by inhaling OVA to induce chronic airway inflammation. By administering DAS, a decrease of the infiltrated inflammatory cell counts and the levels of IL-4 and IL-10 in bronchoalveolar lavage fluid as well as the OVA-specific immunoglobulin E levels in sera were observed. DAS also effectively inhibited OVA-induced inflammatory cell infiltration and mucus hypersecretion in lung tissue. Several OVA-induced inflammatory factors (ROS, 8-hydroxy-2'-deoxyguanosine, 8-iso-prostaglandin F2α, and NF-κB) were inhibited by DAS. In addition, DAS increased OVA inhalation-reduced levels of Nrf2 activation by regulating microRNA-144, -34a and -34b/c. Together, the pathogenesis of OVA-induced asthma is highly associated with oxidative stress, and DAS may be an effective supplement to alleviate this disease.

Recombinant tissue plasminogen activator (t-PA) is the only FDA approved therapy for acute ischemic stroke. Cerebral microbleeds (CMBs) or cerebral amyloid angiopathy (CAA) are currently not contraindications, however, data regarding this complex issue are limited. We report 2 cases of fatal intracerebral hemorrhage (sICH) after IV t-PA, each with evidence of CAA. Patients with CAA may have increased risk for IV thrombolysis-associated sICH. We highlight the severe and catastrophic pattern of ICH, which may be a defining characteristic, and discuss the limitations of our current understanding of the risk of thrombolysis-associated ICH in patients with CAA and/or CMBs.

Increasing oxidative stress is intimately involved in the pathogenesis of lung failure. Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a key element in redox homeostasis. Nrf2 regulates antioxidant-associated genes that are often the target of phytochemicals in chemoprevention. This study evaluated the effect of diallyl sulfide (DAS), which is present in garlic, on the expression of antioxidant enzymes in the rat lung and the Nrf2 modulation in MRC-5 lung cells. DAS increased the activities of glutathione S-transferase, glutathione reductase, and catalase as well as the GSH/GSSG ratio compared with the lung of untreated control rats (p < 0.05). The pulmonic superoxide dismutase, glutathione peroxidase, NAD(P)H:quinone oxidoreductase 1, and catalase mRNA levels were also significantly increased (p < 0.05) after DAS treatment. Following DAS treatment, DAS level was measured in the plasma after 7 days of oral administration, and the C(max) value was 15 ± 4.2 μM. The total amount of pulmonic Nrf2 and the nuclear translocation of Nrf2 were elevated in DAS-treated rats, clarifying the effect of DAS on the modulation of antioxidant enzymes. Furthermore, DAS could induce nuclear translocation of Nrf2 via ERK/p38 signaling pathway in lung MRC-5 cells. This study demonstrates that DAS administration can significantly induce the activity of antioxidant enzymes in rat lungs and suggests a possible use for DAS as a dietary preventive agent against oxidative stress-induced lung injury.