Status epilepticus suspected autoimmune: Neuronal surface antibodies and main clinical features.

OBJECTIVES: Status epilepticus (SE) can be associated with neuronal surface antibodies (NS-Abs) but NS-Ab detection rate remains unknown in patients with SE of unclear etiology at symptom presentation but suspected of having an autoimmune etiology (SE suspected autoimmune). We aimed to determine the NS-Ab detection rate and the clinical features that predict the presence of NS-Abs in patients with SE suspected autoimmune. METHODS: We retrospectively reviewed the clinical information of 137 patients with SE suspected autoimmune who underwent testing for NS-Abs between January 2007 and September 2020. NS-Abs were examined in both serum and cerebrospinal fluid (CSF) obtained at symptom onset with established assays. We classified brain magnetic resonance imaging (MRI) findings into unremarkable, autoimmune limbic encephalitis (ALE) (bilateral abnormalities highly restricted to the medial temporal lobes), ALE-Plus (ALE pattern and additional extramedial temporal lobe abnormalities), multifocal cortico-subcortical (MCS), or other pattern. We compared the clinical features between patients with and without NS-Abs. RESULTS: Forty-four patients (32.1%) had NS-Abs, including 35 N-methyl-d-aspartate receptor (NMDAR) (one with concurrent γ-aminobutyric acid B receptor [GABAbR] and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor [AMPAR]), 5 γ-aminobutyric acid A receptor (GABAaR), 2 leucine-rich glioma-inactivated 1(LGI1), 1 GABAbR, and 1 unknown antigens. Compared with NS-Ab-negative patients, NS-Ab-positive patients were more likely to have a preceding headache (56.8% vs 26.7%), preceding psychobehavioral or memory alterations (65.9% vs 20.4%), involuntary movements (79.5% vs 16.1%), CSF pleocytosis (81.8% vs 62.0%), elevated immunoglobulin G (IgG) index (45.2% vs 15.6%), oligoclonal bands (51.5% vs 9.5%), tumor (47.7% vs 8.6%), and higher APE2 score (median of 9 vs 7), and they were less likely to have an ALE-Plus pattern (2.3% vs 23.7%). However, preceding fever and ALE or MCS pattern were not different between the two groups of patients. SIGNIFICANCE: When an autoimmune etiology was suspected, there was a relatively high likelihood (one of three patients) of identifying NS-Abs. Some clinical features (preceding symptoms, inflammatory CSF) predict a higher likelihood of finding NS-Ab positivity, but the ALE-Plus MRI pattern is more likely suggestive of NS-Ab negativity.

Curvature of the left main bronchus caused by postural change from supine to left lateral position.

This study was designed to examine deviation of the bronchus by postural change from supine to lateral position during spontaneous respiration. Fifteen healthy volunteers [13 men and 2 women, mean age: 34 years (range 26-42)] participated. Chest radiograms (anterior-posterior) were acquired in the order of supine, left lateral, and right lateral position. The bilateral bronchus angles and secondary carina angles were measured in the acquired images, and the angles were compared between the supine and lateral positions to evaluate deviation of the bronchus in the lateral position. The left secondary carina angle in the supine position was 61.3° ± 4.0° and it significantly increased to 65.5° ± 6.0° in the left lateral position (P = 0.001), but no significant difference was noted in the left bronchus angle between the supine and left lateral positions (P = 0.158). The curvature of left main bronchus, which we defined more than 5° increase in secondary carina angle, was observed in a half of the male participants during left lateral position. We should be aware of these anatomical changes due to the surgical posture as a possible cause for ventilation failure during one-lung ventilation.

Variations of organic functional chemistry in carbonaceous matter from the asteroid 162173 Ryugu.

Primordial carbon delivered to the early earth by asteroids and meteorites provided a diverse source of extraterrestrial organics from pre-existing simple organic compounds, complex solar-irradiated macromolecules, and macromolecules from extended hydrothermal processing. Surface regolith collected by the Hayabusa2 spacecraft from the carbon-rich asteroid 162173 Ryugu present a unique opportunity to untangle the sources and processing history of carbonaceous matter. Here we show carbonaceous grains in Ryugu can be classified into three main populations defined by spectral shape: Highly aromatic (HA), Alkyl-Aromatic (AA), and IOM-like (IL). These carbon populations may be related to primordial chemistry, since C and N isotopic compositions vary between the three groups. Diffuse carbon is occasionally dominated by molecular carbonate preferentially associated with coarse-grained phyllosilicate minerals. Compared to related carbonaceous meteorites, the greater diversity of organic functional chemistry in Ryugu indicate the pristine condition of these asteroid samples.

High-sensitive XANES analysis at Ce L2-edge for Ce in bauxites using transition-edge sensors: Implications for Ti-rich geological samples.

Accurate determination of cerium (Ce) valence state is important for interpreting the Ce anomaly in geological archives for (paleo)redox reconstruction. However, the routine application of Ce L3-edge X-ray absorption near-edge structure (XANES) spectroscopy for detecting trace Ce in geological samples can often be restricted by coexisting titanium (Ti) due to the proximity of their fluorescence emission lines. Therefore, the signal-to-noise ratio of Ce L3-edge XANES spectra may not be sufficiently high for high-quality spectroscopic analysis. This study introduces a semi-quantitative approach appropriate for Ti-rich, Ce-dilute geological materials by synchrotron-based X-ray measurement at the Ce L2-edge. First, the results confirm that Ce L2-edge XANES spectra are able to avoid overlapping Ti Kß emissions and provide more reliable information on the Ce valence state in Ti-rich materials relative to L3-edge XANES. Moreover, the application of transition-edge sensor (TES) could reach the higher sensitivity with better energy resolution than conventional silicon drift detector (SDD) to detect fluorescence X-ray (Ce Lß1). The investigation on bauxites developed from the Columbia River Basalts shows that combining Ce L2-edge XANES and TES allows for resolving weak Ce fluorescence lines at the L2-edge from Ti-rich, Ce-dilute samples (Ti/Ce mass ratio up to ∼6000, tens of ppm Ce). The outcome emphasizes the practical possibility of investigating Ce redox state in Ti-rich geological samples.

Macromolecular organic matter in samples of the asteroid (162173) Ryugu.

Samples of the carbonaceous asteroid (162173) Ryugu were collected and brought to Earth by the Hayabusa2 spacecraft. We investigated the macromolecular organic matter in Ryugu samples and found that it contains aromatic and aliphatic carbon, ketone, and carboxyl functional groups. The spectroscopic features of the organic matter are consistent with those in chemically primitive carbonaceous chondrite meteorites that experienced parent-body aqueous alteration (reactions with liquid water). The morphology of the organic carbon includes nanoglobules and diffuse carbon associated with phyllosilicate and carbonate minerals. Deuterium and/or nitrogen-15 enrichments indicate that the organic matter formed in a cold molecular cloud or the presolar nebula. The diversity of the organic matter indicates variable levels of aqueous alteration on Ryugu's parent body.

Broadband high-energy resolution hard x-ray spectroscopy using transition edge sensors at SPring-8.

We have succeeded in operating a transition-edge sensor (TES) spectrometer and evaluating its performance at the SPring-8 synchrotron x-ray light source. The TES spectrometer consists of a 240 pixel National Institute of Standards and Technology (NIST) TES system, and 220 pixels are operated simultaneously with an energy resolution of 4 eV at 6 keV at a rate of ∼1 c/s pixel-1. The tolerance for high count rates is evaluated in terms of energy resolution and live time fraction, leading to an empirical compromise of ∼2 × 103 c/s (all pixels) with an energy resolution of 5 eV at 6 keV. By utilizing the TES's wideband spectroscopic capability, simultaneous multi-element analysis is demonstrated for a standard sample. We conducted x-ray absorption near-edge structure (XANES) analysis in fluorescence mode using the TES spectrometer. The excellent energy resolution of the TES enabled us to detect weak fluorescence lines from dilute samples and trace elements that have previously been difficult to resolve due to the nearly overlapping emission lines of other dominant elements. The neighboring lines of As Kα and Pb Lα2 of the standard sample were clearly resolved, and the XANES of Pb Lα2 was obtained. Moreover, the x-ray spectrum from the small amount of Fe in aerosols was distinguished from the spectrum of a blank target, which helps us to understand the targets and the environment. These results are the first important step for the application of high resolution TES-based spectroscopy at hard x-ray synchrotron facilities.

Reactor environment during the Fukushima nuclear accident inferred from radiocaesium-bearing microparticles.

Radiocaesium-bearing microparticles (CsMPs), which are substantially silicate glass, were formed inside the damaged reactor and released to the environment by the Fukushima Dai-ichi Nuclear Power Plant accident in March 2011. The present study reports several valuable findings regarding their composition and structure using advanced microanalytical techniques. X-ray absorption near-edge structure of Fe L3-absorption indicated that the oxidation state of the iron dissolved in the glass matrix of the CsMPs was originally nearly divalent, suggesting that the atmosphere in which the CsMPs were formed during the accident was considerably reductive. Another major finding is that sodium, which has not been recognised as a constituent element of CsMPs thus far, is among the major elements in the glass matrix. The atomic percent of Na is higher than that of other alkali elements such as K and Cs. Furthermore, halite (NaCl) was found as an inclusion inside a CsMP. The existence of Na in CsMPs infers that seawater injected for cooling might reach the inside of the reactor before or during the formation of the CsMPs. These results are valuable to infer the environment inside the reactor during the accident and the debris materials to be removed during the decommissioning processes.

An Another Protocol to Make Sulfur Embedded Ultrathin Sections of Extraterrestrial Small Samples.

Another protocol to make sulfur embedded ultrathin sections was developed for STXM-XANES, AFM-IR and TEM analyses of organic materials in small extraterrestrial samples. Polymerized liquid sulfur-instead of low-viscosity liquid sulfur-is the embedding media in this protocol. Due to high viscosity of the polymerized sulfur, the embedded samples stay near the surface of polymerized liquid sulfur, which facilitates trimming of glassy sulfur and ultramicrotomy of tiny embedded samples. In addition, well-continued ribbons of ultramicrotomed sections can be obtained, which are suitable for the above mentioned analyses. Because there is no remarkable difference in Carbon XANES spectra of Murchison IOM prepared by this protocol and by the conventional protocol, this protocol gives another alternative to prepare sulfur embedded ultramicrotomed sections.

Clinically based score predicting cryptogenic NORSE at the early stage of status epilepticus.

OBJECTIVE: To determine whether a clinically based score predicts cryptogenic new-onset refractory status epilepticus (C-NORSE) at the early stage of status epilepticus (SE) with prominent motor symptoms (SE-M) of unclear etiology. METHODS: The score (range 0-6) included 6 clinical features: highly refractoriness to antiseizure drugs, previously healthy individual, presence of prodromal fever, absence of prodromal psychobehavioral or memory alterations, absence of dyskinesias, and symmetric brain MRI abnormalities (the first 2 mandatory). We retrospectively assessed the usefulness of a high scale score (≥5) in predicting C-NORSE in 83 patients with SE-M of unclear etiology, who underwent testing for neuronal surface antibodies (NS-Abs) between January 2007, and December 2019. RESULTS: Thirty-one (37.3%) patients had a high score. Patients with a high score had more frequent prodromal fever (28/31 vs 24/52), mechanical ventilatory support (31/31 vs 36/52), and symmetric MRI abnormalities (26/31 vs 12/52), had less frequent involuntary movements (2/31 vs 30/52), and had absent prodromal psychobehavioral alterations (0/31 vs 27/52), CSF oligoclonal band detection (0/27 vs 11/38), tumor association (0/31 vs 13/52), or NS-Abs (0/31 vs 29/52) than those with a low score (<5). Thirty-three patients (median age, 27 years; 18 [54.5%] female) were finally regarded as C-NORSE. The sensitivity and specificity of a high score for predicting C-NORSE were 93.9% (95% CI 0.87-0.94) and 100% (95% CI 0.95-1.00), respectively. CONCLUSIONS: Patients with a high score in the indicated scale are more likely to have C-NORSE, making it a useful diagnostic tool at the early stage of SE-M before antibody test results become available.

A cluster of disseminated small cortical lesions in MELAS: its distinctive clinical and neuroimaging features.

OBJECTIVES: To investigate a diversity of stroke-like episodes (SLEs) in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and report a disseminated form of SLEs (D-SLEs) attributed to a cluster of disseminated small cortical lesions. METHODS: We retrospectively reviewed the clinical information of 27 MELAS patients seen at Kitasato University Hospital between January 1990 and April 2018. Among those, we selected 13 patients with m.3243A>G mutation [median age at onset, 35 years (11-68 years), two pediatric onset < 17 years] who had at least one SLE. SLEs were classified into classic or non-classic based on characteristic features of stroke-like lesions. RESULTS: 44 SLEs were identified during a median observational period of 119 months (3-240 months). Among those, 29 (65.9%) were classic SLEs (C-SLEs) mainly attributed to a single continuous lobular lesion incongruent to vascular territory and occasionally accompanied by a gradual spread associated with hyperperfusion and persistent seizure activity. The remaining 15 were non-classic attributed to sparsely distributed (n = 10), disseminated (n = 4) or cerebellar lesions (n = 1). C-SLEs developed in all patients but non-classic SLEs in 5; D-SLEs developed in 4 patients accounting for 4 of 44 SLEs (9.1%). Non-classic SLEs developed more frequently in pediatric-onset than in adult-onset patients (12/15 vs. 3/29, p < 0.0001). SLEs began with acute onset of symptoms in 42 SLEs (95.5%), but D-SLEs of 2 adult-onset patients began with ill-defined subacute-onset fluctuating encephalopathy. CONCLUSIONS: This study showed a diversity of SLEs in patients with m.3243A>G mutation. Further studies are required to elucidate the pathophysiological mechanisms of non-classic SLEs including D-SLEs.

Correction to: A cluster of disseminated small cortical lesions in MELAS: its distinctive clinical and neuroimaging features.

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A novel organic-rich meteoritic clast from the outer solar system.

The Zag meteorite which is a thermally-metamorphosed H ordinary chondrite contains a primitive xenolithic clast that was accreted to the parent asteroid after metamorphism. The cm-sized clast contains abundant large organic grains or aggregates up to 20 µm in phyllosilicate-rich matrix. Here we report organic and isotope analyses of a large (~10 µm) OM aggregate in the Zag clast. The X-ray micro-spectroscopic technique revealed that the OM aggregate has sp2 dominated hydrocarbon networks with a lower abundance of heteroatoms than in IOM from primitive (CI,CM,CR) carbonaceous chondrites, and thus it is distinguished from most of the OM in carbonaceous meteorites. The OM aggregate has high D/H and 15N/14N ratios (δD = 2,370 ± 74‰ and δ15N = 696 ± 100‰), suggesting that it originated in a very cold environment such as the interstellar medium or outer region of the solar nebula, while the OM is embedded in carbonate-bearing matrix resulting from aqueous activities. Thus, the high D/H ratio must have been preserved during the extensive late-stage aqueous processing. It indicates that both the OM precursors and the water had high D/H ratios. Combined with 16O-poor nature of the clast, the OM aggregate and the clast are unique among known chondrite groups. We further propose that the clast possibly originated from D/P type asteroids or trans-Neptunian Objects.

Significant contribution of subseafloor microparticles to the global manganese budget.

Ferromanganese minerals are widely distributed in subseafloor sediments and on the seafloor in oceanic abyssal plains. Assessing their input, formation and preservation is important for understanding the global marine manganese cycle and associated trace elements. However, the extent of ferromanganese minerals buried in subseafloor sediments remains unclear. Here we show that abundant (108-109 particles cm-3) micrometer-scale ferromanganese mineral particles (Mn-microparticles) are found in the oxic pelagic clays of the South Pacific Gyre (SPG) from the seafloor to the ~100 million-year-old sediments above the basement. Three-dimensional micro-texture, and major and trace element compositional analyses revealed that these Mn-microparticles consist of poorly crystalline ferromanganese oxides precipitating from bottom water. Based on our findings, we extrapolate that 1.5-8.8 × 1028 Mn-microparticles, accounting for 1.28-7.62 Tt of manganese, are globally present in oxic subseafloor sediments. This estimate is at least two orders of magnitude larger than the manganese budget for nodules and crusts on the seafloor. Subseafloor Mn-microparticles thus contribute significantly to the global manganese budget.

Yokukansan (Kampo medicinal formula) prevents the development of morphine tolerance by inhibiting the secretion of orexin A.

BACKGROUND: Yokukansan (YKS), a traditional herbal (Kampo) medicine consisting of seven herbs, is effective in the treatment of pain disorders, such as headache, postherpetic neuralgia, fibromyalgia, and trigeminal neuralgia, and we have previously shown it to be effective against morphine analgesic tolerance in rats. It has been reported that orexin receptor antagonists prevent the development of morphine tolerance and that YKS inhibits the secretion of orexin A in the hypothalamus. This study examined whether the inhibition of the secretion of orexin A by YKS is one mechanism underlying its effect against morphine analgesic tolerance. METHODS: Male Wistar rats were administered a subcutaneous injection of morphine hydrochloride (10 mg/kg/day) for 5 days. One group was preadministered YKS, starting 3 days before the morphine. The withdrawal latency following thermal stimulation was measured daily using a hot plate test. On day 5, the levels of orexin A in the plasma and the midbrain were measured, and the appearance of activated astrocytes in the midbrain was examined by immunofluorescence staining. RESULTS: The preadministration of YKS prevented the development of morphine tolerance. The repeated administration of morphine significantly increased the plasma and midbrain levels of orexin A and the activation of astrocytes. These increases were significantly inhibited by the preadministration of YKS. CONCLUSION: These results suggest that the preadministration of YKS attenuated the development of antinociceptive morphine tolerance and that the inhibition of orexin A secretion may be one mechanism underlying this phenomenon.

Practical issues in measuring autoantibodies to neuronal cell-surface antigens in autoimmune neurological disorders: 190 cases.

OBJECTIVES: To address practical issues in measuring autoantibodies to neuronal cell-surface antigens (NSAs) in various autoimmune neurological disorders (ANDs). METHODS: We retrospectively reviewed the clinical information of 221 patients with clinically suspected ANDs who underwent antibody testing for NSAs between January 2007 and September 2017. 31 were excluded. In 190 patients, antibody-detection rate (ADR) and antibody-phenotype association were assessed. RESULTS: Fifty-four patients had NSA-antibodies: NMDA receptor (NMDAR) (n = 39), AMPA receptor (n = 3), leucine-rich glioma inactivated 1 (LGI1) (n = 3), glycine receptor (GlyR) (n = 3), GABA(A) receptor (n = 2), GABA(B) receptor (n = 1), metabotrophic glutamate receptor 5 (n = 1), or unknown (n = 6); 3 had multiple NSA-antibodies. ADR in patients with diagnostic criteria for "possible autoimmune encephalitis (AE)", "probable anti-NMDAR encephalitis", "definite autoimmune limbic encephalitis (ALE)", and "stiff-person spectrum disorder (SPSD)", was 34% (46/134), 85% (34/40), 46% (11/24), and 22% (4/18), respectively, but NSA-antibodies were not identified in 11 patients with systemic autoimmune disorders (SADs). Among 134 patients with "possible AE" criteria, NMDAR-antibodies were more frequently identified in patients with typical anti-NMDAR encephalitis than those without (34/40 [85%] vs. 4/94 [4%], p < 0.0001). LGI1-antibodies were identified in patients with ALE but not in the others (3/24 [13%] vs. 0/110 [0%], p = 0.005). GlyR-antibodies were identified in those with stiff-person syndrome plus (2/8, 25%) or stiff-limb syndrome (1/6, 17%). CONCLUSIONS: NSA-antibodies were most frequently identified in "probable anti-NMDAR encephalitis", followed by "definite ALE", "possible AE", and "SPSD", but not identified in SADs. NMDAR, LGI1 and GlyR were associated with clinical phenotype. Cell-surface antigens should be determined based on individual phenotype.

Organic matter in extraterrestrial water-bearing salt crystals.

Direct evidence of complex prebiotic chemistry from a water-rich world in the outer solar system is provided by the 4.5-billion-year-old halite crystals hosted in the Zag and Monahans (1998) meteorites. This study offers the first comprehensive organic analysis of the soluble and insoluble organic compounds found in the millimeter-sized halite crystals containing brine inclusions and sheds light on the nature and activity of aqueous fluids on a primitive parent body. Associated with these trapped brines are organic compounds exhibiting wide chemical variations representing organic precursors, intermediates, and reaction products that make up life's precursor molecules such as amino acids. The organic compounds also contain a mixture of C-, O-, and N-bearing macromolecular carbon materials exhibiting a wide range of structural order, as well as aromatic, ketone, imine, and/or imidazole compounds. The enrichment in 15N is comparable to the organic matter in pristine Renazzo-type carbonaceous chondrites, which reflects the sources of interstellar 15N, such as ammonia and amino acids. The amino acid content of the Zag halite deviates from the meteorite matrix, supporting an exogenic origin of the halite, and therefore, the Zag meteorite contains organics synthesized on two distinct parent bodies. Our study suggests that the asteroidal parent body where the halite precipitated, potentially asteroid 1 Ceres, shows evidence for a complex combination of biologically and prebiologically relevant molecules.

Cyanobacterial exopolymer properties differentiate microbial carbonate fabrics.

Although environmental changes and evolution of life are potentially recorded via microbial carbonates, including laminated stromatolites and clotted thrombolites, factors controlling their fabric are still a matter of controversy. Herein, we report that the exopolymer properties of different cyanobacterial taxa primarily control the microbial carbonates fabrics in modern examples. This study shows that the calcite encrustation of filamentous Phormidium sp. secreting acidic exopolymers forms the laminated fabric of stromatolites, whereas the encrustation of coccoid Coelosphaeriopsis sp. secreting acidic exopolymers and poor calcification of filamentous Leptolyngbya sp. secreting non-acidic exopolymers form peloids and fenestral structures, respectively, i.e. the clotted fabric of thrombolites. Based on these findings, we suggest that the rise and decline of cyanobacteria possessing different exopolymer properties caused the expansion of thrombolites around the Proterozoic/Cambrian boundary.

Comparison of Solid-Water Partitions of Radiocesium in River Waters in Fukushima and Chernobyl Areas.

Adsorption of radiocesium (RCs) on particulate matters in aquatic environment is important to understand its mobility and bioavailability. We here focused on factors controlling partition of RCs on particulate matters and sediments in Kuchibuto (Fukushima) and Pripyat (Chernobyl) Rivers, though RCs level in water was much smaller than WHO guideline. Moreover, Cs speciation and organic matter-clay mineral interaction were studied: (i) extended X-ray absorption fine structure showed that the contribution of outer-sphere complex of Cs on particulate matters is larger in Chernobyl than in Fukushima and (ii) scanning transmission X-ray microscope revealed larger association of humic substances and clay minerals in Chernobyl partly due to high [Ca2+] in the Pripyat River. Consequently, RCs is more soluble in the Pripyat River due to weaker interaction of RCs with clay minerals caused by the inhibition effect of the adsorbed humic substances. In contrast, particulate matters and sediments in the Kuchibuto River display high adsorption affinity with lesser inhibition effect of adsorbed humic substances. This difference is possibly governed by the geology and soil type of provenances surrounding both catchments (Fukushima: weathered granite; Chernobyl: peat wetland and carbonate platform) which leads to high concentrations of organic matter and Ca2+ in the Pripyat River.

Spatially Resolved Distribution of Fe Species around Microbes at the Submicron Scale in Natural Bacteriogenic Iron Oxides.

Natural bacteriogenic iron oxides (BIOS) were investigated using local-analyzable synchrotron-based scanning transmission X-ray microscopy (STXM) with a submicron-scale resolution. Cell, cell sheath interface (EPS), and sheath in the BIOS were clearly depicted using C-, N-, and O- near edge X-ray absorption fine structure (NEXAFS) obtained through STXM measurements. Fe-NEXAFS obtained from different regions of BIOS indicated that the most dominant iron mineral species was ferrihydrite. Fe(II)- and/or Fe(III)-acidic polysaccharides accompanied ferrihydrite near the cell and EPS regions. Our STXM/NEXAFS analysis showed that Fe species change continuously between the cell, EPS, and sheath under several 10-nm scales.

Yokukansan, a Kampo medicine, prevents the development of morphine tolerance through the inhibition of spinal glial cell activation in rats.

BACKGROUND: Animal models have shown that glial cells (microglia and astrocytes) in the spinal cord undergo activation following peripheral injury associated with chronic pain, suggesting the involvement of these cells in pain diseases. We have previously reported that Yokukansan (YKS), a Japanese traditional herbal (Kampo) medicine, is effective against chronic pain through the suppression of spinal glial cell activation. Morphine is a widely-used opioid analgesic for relieving severe pain, but its repeated administration leads to the development of antinociceptive tolerance. The development of morphine tolerance is also reported to be caused by spinal glial cells activation. In the present study, we investigated the inhibitory effects of YKS on the development of morphine tolerance and the activation of the spinal microglia and astrocytes using a rat model. METHODS: Male Wistar rats received a subcutaneous injection of morphine hydrochloride (10 mg/kg/d) for 7 days, and the withdrawal latency to thermal stimulation was measured daily using a hot plate test. Thereafter, the appearance of activated microglia and astrocyte in the spinal cord (L5) was examined by immunofluorescence staining. Ionized calcium binding adapter molecule-1 (Iba-1) staining was used to label microglia and glial fibrillary acidic protein (GFAP) staining was performed to label astrocytes. YKS was administered mixed with powdered rodent chow at a concentration of 3%. RESULTS: The preadministration of YKS (started 3 d before the morphine injection) prevented the development of morphine tolerance. The repeated administration of morphine increased Iba-1 and GFAP immune reactivities in the spinal cord; however, these activations were inhibited by the preadministration of YKS. CONCLUSION: These results suggest that the preadministration of YKS attenuates the development of antinociceptive morphine tolerance, and the suppression of spinal glial cell activation may be one mechanism underlying this phenomenon.