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Background and Study Aims: Esophageal restenosis is a serious complication after esophageal stent placement, which influences the clinical prognosis of stent implantation and the patient's quality of life. TGF-β1/Smads signaling pathway plays an important role in the development of the eosinophilic esophagitis and scar repair after skin trauma. However, the role of TGF-β1/Smads in the development of esophageal restenosis after esophageal stent placement remains unknown. Our study aimed to investigate whether TGF-β1/Smads plays an important role in the development of esophageal restenosis after esophageal stent, and whether the exogenous TGF-β1 inhibitor supplement could ameliorate the esophageal restenosis after esophageal stent., Material and Methods: We established the model of esophageal restenosis after esophageal stenting in rats, and determined the expression levels of TGF-β1/Smads signaling pathway and the relevant markers of fibroblast activation by immunochemistry (IHC), Western Blot and real time qPCR. Those all the indicators were also determined in esophageal fibroblast when exposed to rhTGF-β1 with or without TGF-β1 inhibitor P144., Results: The serum level of IL-1β and TNFα were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. The TGF-β1/Smads signaling pathway and the relevant markers of fibroblast activation were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. Those all the indicators were significantly increased when exposed to rhTGF-β1, and obviously decreased when treated with P144., Conclusions: TGF-β1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-β1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Purpose: To stratify angiographic images of chronic internal carotid artery occlusion (CICAO) into a newly modified angiographic classification, and identify suitable candidates for endovascular recanalization., Methods: This study included 51 consecutive patients with symptomatic CICAO who underwent endovascular recanalization at our institution. Patients' clinical information, angiographic findings, procedural results, and outcomes were recorded. We attempted to stratify all angiographic images into categories based on morphological occlusive patterns and distal internal carotid artery (ICA) lumen reconstitution on digital subtraction angiography (DSA)., Results: Four types (I-IV) of CICAO were identified based on angiographic characteristics. We defined type I as having a tapered (IA) or blunt stump (IB) and distal ICA lumen reconstitution with collateral filling; type II as having no stump but with distal ICA lumen reconstitution; type III as having a tapered (IIIA) or blunt stump (IIIB) but no distal ICA lumen reconstitution; type IV as having no stump and no distal ICA lumen reconstitution. The rate of successful recanalization was 90.3 % for type I, 60.0 % for type II, 50.0 % for type III, 0 % for type IV, respectively (P = 0.002). The overall intraoperative complication rate was 11.8 %, and none of them led to severe neurological damage or death. The follow-up modified Rankin Scale (mRS) scores were significantly decreased in successfully revascularized patients, whilst there were no significant changes in the other failed patients., Conclusion: For symptomatic CICAO, our newly modified angiographic classification may be comprehensive and useful in selecting suitable patients for recanalization and grading the difficulty of the procedures., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The predictors of futile recanalization in patients with intracranial atherosclerosis (ICAS)-related stroke are not understood. This study aimed to identify the predictors of futile recanalization after endovascular treatment (EVT) in patients who experience an acute stroke caused by ICAS-related occlusion., Methods: We retrospectively reviewed the data of patients with ICAS-related stroke who underwent EVT from January 2018 to July 2021. Futile recanalization was defined as functional dependence (modified Rankin scale 3-6) despite successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2 b/3). Multivariate logistic regression analysis was used to determine the risk factors associated with futile recanalization. The receiver operating characteristic curve was used to examine the predictive value of the risk prediction model for futile recanalization., Results: Of the 87 patients enrolled, futile recanalization was observed in 32 (36.8%). Multivariate logistic analysis showed that older age (OR, 1.05; 95% CI, 1.01-1.10; P = 0.026), a higher National Institutes of Health Stroke Scale (NIHSS) score on admission (OR, 1.25; 95% CI, 1.08-1.45; P = 0.003), and poor collaterals (OR, 5.49; 95% CI, 1.70-17.79; P = 0.004) were independently associated with futile recanalization after EVT in patients with ICAS-related stroke. The receiver operating characteristic curve showed that the model in combination with age, admission NIHSS score, and collateral status could accurately predict futile recanalization in these patients (areas under the curve, 0.85; 95% CI, 0.76-0.92; P < 0.001)., Conclusions: Older age, higher NIHSS score on admission, and poor collaterals are predictors of futile recanalization in patients with ICAS-related stroke., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: To retrospectively evaluate the safety and efficacy of computed tomography (CT)-guided iodine-125 ( 125 I) seed implantation for patients with abdominal incision metastases from colorectal cancer., Materials and Methods: Data of patients with abdominal incision metastases of colorectal cancer from November 2010 to October 2020 were retrospectively reviewed. Each incisional metastasis was percutaneously treated with 125 I seed implantation under CT guidance. Follow-up contrast-enhanced CT was reviewed, and the outcomes were evaluated in terms of objective response rate, complications, and overall survival., Results: A total of 17 patients were enrolled in this study. The median follow-up was 18 months (range, 2.7-22.1 months). At 3, 6, 12, and 18 months after the treatment, objective response rate was 52.9%, 63.6%, 33.3%, and 0%, respectively. A small amount of local hematoma occurred in two patients and resolved spontaneously without any treatment. Two patients experienced a minor displacement of radioactive seeds with no related symptoms. Severe complications, such as massive bleeding and radiation injury, were not observed. No ≥ grade 3 adverse events were identified. By the end of follow-up, 14 patients died of multiple hematogenous metastases. The one-year overall survival rate was 41.6%, and the median overall survival was 8.6 months., Conclusion: CT-guided 125 I seed implantation brachytherapy is safe and feasible for patients with abdominal incision metastases from colorectal cancer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The standard rescue modality for patients with intracranial atherosclerotic stenosis after failed mechanical thrombectomy (MT) is not well established. We evaluated the safety and efficacy of balloon dilation in combination with tirofiban as the first-line salvage therapy when MT failed in these patients., Methods: We retrospectively analyzed the records of 47 patients admitted between January 2018 and June 2021, with middle cerebral artery atherosclerotic occlusion, who underwent balloon angioplasty in combination with tirofiban as the first-line salvage therapy after the failure of MT. The recanalization outcome, procedure-related complications, symptomatic intracranial hemorrhage, and functional outcome at 90 days were reviewed., Results: Recanalization with a modified Thrombolysis in Cerebral Infarction grade of 2b-3 was achieved in 41 (87.2%) of the 47 patients. Acute stents were deployed in another 6 patients who did not achieve successful re-perfusion after balloon angioplasty. Successful recanalization was achieved in 3 of them. One patient (2.1%, 1/47) experienced re-occlusion several days later due to the withdrawal of antiplatelet therapy for parenchymal hematoma. Seven patients (14.9%, 7/47) underwent stent angioplasty in the stable stage (range: 1-2 months) because severe residual stenosis was detected on follow-up imaging. There was only one event of periprocedural complication, namely ectopic migration of emboli. The good functional outcome rate was 55.3% (26/47), without the events of symptomatic intracranial hemorrhage and mortality., Conclusions: Balloon angioplasty in combination with tirofiban is safe and effective for middle cerebral artery atherosclerotic occlusion after the failure of MT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To evaluate the prognostic significance of high-sensitivity cardiac troponin T (hs-cTnT) elevation in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) in the anterior circulation treated with endovascular thrombectomy (ET) in late time windows and identify the factors associated with hs-cTnT elevation., Methods: A total of 152 AIS patients treated with ET in late time windows between January 2018 and August 2020 were included in this study. Patients were stratified into either normal or elevated hs-cTnT groups according to a cutoff value of 14 ng/L on admission. Baseline demographic features, comorbidities, and imaging data were compared between the elevated hs-cTnT group (＞14 ng/L) and the normal hs-cTnT group (≤14 ng/L). After accounting for these clinical characteristics, the association between hs-cTnT elevation and clinical outcomes was evaluated., Results: 69(45.4%) patients had elevated hs-cTnT levels (>14 ng/L) on admission. The multivariable logistic regression analysis demonstrated that hs-cTnT elevation was independently associated with 3-month all-cause mortality (P = 0.014, OR 3.907, 95% CI 1.313-11.625) and 3-month composite unfavorable outcome (mRS 3-6) (P = 0.001, OR 5.099, 95% CI 1.873-13.888). Old age (P = 0.002, OR 1.053, 95% CI 1.020-1.088), admission NIHSS score (P = 0.015, OR 1.057, 95% CI 1.011-1.106), congestive heart failure (P = 0.016, OR 4.341, 95% CI 1.322-14.257) and coronary artery disease (P = 0.020, OR 2.914, 95% CI 1.183-7.180) were independently associated with hs-cTnT elevation., Conclusion: In AIS patients treated with ET in late time windows, elevated hs-cTnT is independently associated with an increased risk of 3-month poor outcomes. Old age, high admission NIHSS score, coronary artery disease, and congestive heart failure are independent predictors of hs-cTnT elevation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: This study aimed to investigate the safety and efficacy of endovascular embolization for very small ruptured anterior communicating artery (AcomA) aneurysms., Methods: From August 2015 to June 2020, 81 patients with very small (≤3 mm) ruptured AcomA aneurysms treated endovascularly were enrolled in this study. Clinical and radiographic data were analyzed retrospectively, including the aneurysm occlusion rate, complications, and clinical outcome., Results: Among 81 patients, simple coiling embolization was performed in 52 cases and stent-assisted embolization in 29 cases. Immediate angiography demonstrated complete occlusion in 59 (72.8%) aneurysms, residual neck in 20 (24.7%) aneurysms, and residual lumen in 2 (2.5%). Procedure-related complications rate was 2.5% (2 of 81), all of which were transient thromboembolic events. Angiographic follow-up outcomes of 60 patients (mean: 6.8 ± 3.2 months) revealed complete occlusion in 91.7% (55 of 60), with recurrence in 1 patient. The mean clinical follow-up time was 22.6 ± 11.4 months and good prognosis rates (6-month modified Rankin Scale score: 0-2) reached 90.2% (73 of 81). The differences in aneurysm occlusion and procedure-related complications between the simple coiling group and the stent-assisted coiling group were not statistically significant., Conclusions: Coiling with or without stent-assisted technique for the treatment of very small ruptured AcomA aneurysms was safe and effective., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background & Aims: Placement of an irradiation stent has been demonstrated to offer longer patency and survival than an uncovered self-expandable metallic stent (SEMS) in patients with unresectable malignant biliary obstruction (MBO). We aim to further assess the efficacy of an irradiation stent compared to an uncovered SEMS in those patients., Methods: We performed a randomized, open-label trial of participants with unresectable MBO at 20 centers in China. A total of 328 participants were allocated in parallel to the irradiation stent group (ISG) or the uncovered SEMS group (USG). Endpoints included stent patency (primary), technical success, relief of jaundice, overall survival, and complications., Results: The first quartile stent patency time (when 25% of the patients experienced stent restenosis) was 212 days for the ISG and 104 days for the USG. Irradiation stents were significantly associated with a decrease in the rate of stent restenosis (9% vs. 15% at 90 days; 16% vs. 27% at 180 days; 21% vs. 33% at 360 days; p = 0.010). Patients in the ISG obtained longer survival time (median 202 days vs. 140 days; p = 0.020). No significant results were observed in technical success rate (93% vs. 95%; p = 0.499), relief of jaundice (85% vs. 80%; p = 0.308), and the incidence of grade 3 and 4 complications (8.5% vs. 7.9%; p = 0.841)., Conclusions: Insertion of irradiation stents instead of uncovered SEMS could improve patency and overall survival in patients with unresectable MBO., Lay Summary: For patients with unresectable malignant biliary obstruction (MBO), placement of a self-expandable metallic stent (SEMS) is a recommended palliative modality to relieve pruritus, cholangitis, pain, and jaundice. However, restenosis is a main pitfall after stent placement. Data from this first multicenter randomized controlled trial showed that insertion of an irradiation stent provided longer patency and better survival than a conventional metal stent. ClinicalTrials.gov ID: NCT02001779., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The aim of our study is to compare the image quality of readout-segmented echo-planar imaging (rs-EPI) and that of standard single-shot EPI (ss-EPI) in orbital 3 T diffusion-weighted (DW) magnetic resonance (MR) imaging in healthy subjects. Forty-two volunteers underwent two sets of orbital DW imaging scan at a 3 T MR unit, and image quality was assessed qualitatively and quantitatively. As a result, we found that rs-EPI could provide better image quality than standard ss-EPI, while no significant difference was found on the apparent diffusion coefficient between the two sets of DW images., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Hyperbilirubinemia is a common clinical phenomenon observed in human newborns. A high level of bilirubin can result in severe jaundice and bilirubin encephalopathy. However, the cellular mechanisms underlying bilirubin excitotoxicity are unclear. Our previous studies showed the action of gamma-aminobutyric acid (GABA)/glycine switches from excitatory to inhibitory during development in the ventral cochlear nucleus (VCN), one of the most sensitive auditory nuclei to bilirubin toxicity. In the present study, we investigated the roles of GABAA/glycine receptors in the induction of bilirubin hyperexcitation in early developing neurons. Using the patch clamp technique, GABAA/glycine receptor-mediated spontaneous inhibitory synaptic currents (sIPSCs) were recorded from bushy and stellate cells in acute brainstem slices from young mice (postnatal day 2-6). Bilirubin significantly increased the frequency of sIPSCs, and this effect was prevented by pretreatments of slices with either fast or slow Ca(2+) chelators BAPTA-AM and EGTA-AM suggesting that bilirubin can increase the release of GABA/glycine via Ca(2+)-dependent mechanisms. Using cell-attached recording configuration, we found that antagonists of GABAA and glycine receptors strongly attenuated spontaneous spiking firings in P2-6 neurons but produced opposite effect in P15-19 neurons. Furthermore, these antagonists reversed bilirubin-evoked hyperexcitability in P2-6 neurons, indicating that excitatory action of GABA/glycinergic transmission specifically contribute to bilirubin-induced hyperexcitability in the early stage of development. Our results suggest that bilirubin-induced enhancement of presynaptic release GABA/Glycine via Ca(2+)-dependent mechanisms may play a critical role in mediating neuronal hyperexcitation associated with jaundice, implicating potential new strategies for predicting, preventing, and treating bilirubin neurotoxicity., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Dynamic contrast enhanced (DCE) MR renography has been identified as an interesting tool to determine single-kidney GFR. However, a fundamental issue for the applicability of MR-based estimate of single-kidney GFR is selecting a balance between spatial and temporal resolution of DCE-MRI data. The purpose is to assess the feasibility of GFR estimate from high-resolution (HR) dynamic contrast-enhanced (DCE) MRI in a routine clinical modal. Standard MR renography (2.4s/phase, total 4min; 4-ml Gd) and five-phase, HR-based imaging protocol (0, 30, 70, 120, and 240s; 0.05mmol/kg Gd) were prospectively performed in twelve volunteers who were scheduled for routine renal MRI. Data were plotted with Patlak, two-compartment modified Tofts model (2CTM), and two-compartment filtration model (2CFM) for GFR estimate. During all the measurements, only the signal intensities in the aorta and whole kidney parenchyma were considered. Standard 2CFM and 2CTM produced lower residuals over the fitted interval than HR-based measures (p<0.05); and HR-bases 2CFM and 2CTM did not reflect significant correlation to standard values. Standard Patlak plots with 0-240s data points produced significantly lower GFR and higher residuals than that plots with 0-120s data points (p<0.05). HR-based Patlak plots with 0, 30, 70, and 120s data points significantly correlated with reference values (Pearson ρ=0.97, p<0.01), and produced a 33.2% underestimation of reference value, which was better than that plots with 0, 30, 70, 120, and 240s data points (ρ=0.92, p<0.01; 58.6% underestimation of reference value). It concludes that it is feasible to estimate GFR with HR-based DCE-MRI and appreciate kinetic model. Patlak plots from 0, 30, 70, and 120s data points is better than plots from 0, 30, 70, 120, and 240s data points., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To investigate diagnostic performance of diffusion kurtosis imaging with histogram analysis for stratifying pathologic Gleason grade of prostate cancer (PCa)., Materials and Methods: This retrospective study was approved by the institutional review board, and written informed consent was waived. A total of 110 patients pathologically confirmed as having PCa (diameter>0.5 cm) underwent preoperative diffusion-weighted magnetic resonance imaging (b value of 0-2,100 s/mm(2)) at 3T. Data were postprocessed by monoexponential and diffusion kurtosis models for quantitation of apparent diffusion coefficients (ADCs), apparent diffusion for Gaussian distribution (D(app)), and apparent kurtosis coefficient (K(app)). The measurement was based on an entire-tumor histogram analysis approach. The ability of imaging indices for differentiating low-grade (LG) PCa (Gleason score [GS]≤6) from intermediate-/high-grade (HG: GS>6) PCa was analyzed by receiver operating characteristic regression., Results: There were 49 LG tumors and 77 HG tumors at pathologic findings. HG-PCa had significantly lower ADCs, lower diffusion kurtosis diffusivity (D(app)), and higher kurtosis coefficient (K(app)) in mean, median, 10th, and 90th percentile, with higher D(app) in skewness and kurtosis than LG-PCa (P< 0.05). The 10th ADCs, the 10th D(app), and the 90th K(app) showed relatively higher area under receiver operating characteristic curve (Az), Youden index, and positive likelihood ratio in stratifying aggressiveness of PCa against other indices. The 90th K(app) showed relatively higher correlation (ρ>0.6) with ordinal GS of PCa; significantly higher Az, sensitivity, and specificity (0.889, 74.1%, and 93.9%, respectively) than the 10th D(app) did (0.765, 61.0%, and 79.6%, respectively; P<0.05); and higher Az and specificity than the 10th ADCs did (0.738 and 71.4%, respectively; P<0.05) in differentiating LG-PCa from HG-PCa., Conclusions: It demonstrated a good reliability of histogram diffusion kurtosis imaging for stratifying pathologic GS of PCa. The 90th K(app) had better diagnostic performance in differentiating LG-PCa from HG-PCa., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Fatty acid synthase (FASN) is known as a crucial enzyme of cellular de novo fatty acid synthesis in mammary gland which has been proved as the main source of short and medium-chain fatty acids of milk. However, the regulatory role of FASN in goat-specific milk fatty acids composition remains unclear. We cloned and analyzed the full-length of FASN gene from the mammary gland of Capra hircus (Xinong Saanen dairy goat) (DQ 915966). Comparative gene expression analysis suggested that FASN is predominantly expressed in fat, small intestine and mammary gland tissues, and expresses higher level at lactation period. Inhibition of FASN activity by different concentrations (0, 5, 15, 25 and 35 μM) of orlistat, a natural inhibitor of FASN, resulted in decreased expression of acetyl-CoA carboxylase α (ACCα), lipoprotein lipase and heart-type fatty acid binding protein (H-FABP) in a concentration-dependent manner in goat mammary gland epithelial cells (GMEC). Similar results were also obtained by silencing of FASN. Additionally, reduction of FASN expression also led to apparent decline of the relative content of decanoic acid (C10:0) and lauric acid (C12:0) in GMEC. Our study provides a direct evidence for inhibition of FASN reduces cellular medium-chain fatty acids synthesis in GMEC.

Mon1 protein is involved in cytoplasm-to-vacuole trafficking, vacuolar morphology and autophagy, and is required for homotypic vacuole fusion in Saccharomyces cerevisiae. Here we identify MoMON1 from Magnaporthe oryzae as an ortholog of S. cerevisiae MON1, essential for the morphology of the vacuole and vesicle fusion. Target gene deletion of MoMON1 resulted in accumulation of small punctuate vacuoles in the hypha and hypersensitivity to monensin, an antibiotic that blocks intracellular protein transport. The ΔMomon1 mutant exhibited significantly reduced aerial hyphal development and poor conidiation. Conidia of ΔMomon1 were able to differentiate appressoria. However, ΔMomon1 was non-pathogenic on rice leaves, even after wound inoculation. In addition, ΔMomon1 was slightly hypersensitive to Congo red and SDS, but not to cell wall degrading enzymes, suggesting significant alterations in its cell wall. The autophagy process was blocked in the ΔMomon1 mutant. Taken together, our results suggest that MoMON1 has an essential function in vacuolar assembly, autophagy, fungal development and pathogenicity in M. oryzae., (Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Hyperbilirubinemia is one of the most common clinical phenomena observed in human newborns. To achieve effective therapeutic treatment, numerous studies have been done to determine the molecular mechanisms of bilirubin-induced neuronal excitotoxicity. However, there is no conclusive evidence for the involvement of glutamatergic synaptic transmission in bilirubin-induced neuronal hyperexcitation and excitotoxicity. In the present study, using gramicidin-perforated patch-clamp techniques, spontaneous excitatory postsynaptic currents (sEPSCs) were recorded from lateral superior olive (LSO) neurons isolated from postnatal 11-14-day-old (P11-14) rats. The application of 3 μM bilirubin increased the frequency, but not the amplitude, of sEPSCs. The action of bilirubin was tetrodotoxin (TTX)-insensitive, as bilirubin also increased the frequency, but not the amplitude, of mEPSCs. The amplitudes of GABA-activated (I(GABA)) and glutamate-activated (I(glu)) currents were not affected by bilirubin. Under current-clamp conditions, no spontaneous action potentials were observed in control solution. However, the application of 3 μM bilirubin for 4-6 min evoked a considerable rate of action-potential firing. The evoked firing was partially occluded by D,L-2-amino-5-phosphonovaleric acid (APV), an NMDA receptor antagonist, but completely inhibited by a combination of APV and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX), an AMPA receptor antagonist. These results indicate that bilirubin facilitates presynaptic glutamate release, enhances glutamatergic synaptic transmission by activating postsynaptic AMPA and NMDA receptors, and leads to neuronal hyperexcitation. This study provides a better understanding of the mechanism of bilirubin-induced excitotoxicity and determines for the first time that both AMPA and NMDA receptors are likely involved in the excitotoxicity produced by bilirubin., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Bilirubin is a well-known neurotoxin that can result in multiple neurologic deficits. Previous studies have suggested that bilirubin affects aspects of synaptic transmission; however the acute effects of bilirubin on synaptic transmission have not been examined in real-time. In this study, using whole-cell voltage-clamp recordings, we observed the effect of bilirubin on inhibitory postsynaptic currents (IPSC) in postnatal 13-15-day-old neurons dissociated from lateral superior olive nuclei (LSO), one of the brainstem auditory nucleus that are highly vulnerable to bilirubin. The results showed that 10(-5)M bilirubin increased the frequency of spontaneous IPSC without causing change in their amplitudes or in the response to bath applied glycine, suggesting a presynaptic locus for the action. In the presence of tetrodotoxin, the frequency of miniature IPSC was also potentiated by 10(-5)M bilirubin. The facilitation by bilirubin was concentration dependent and increased with an increase in exposure time. Bicuculline only partially reduced the action of bilirubin. The action of bilirubin was observed in extracellular Ca(2+)-free ([Ca(2+)](o) free) solution but was fully occluded by pretreatment with BAPTA-AM in [Ca(2+)](o) free solution. Thus, in LSO neurons, bilirubin facilitates inhibitory synaptic transmission, in a manner independent of voltage-activated Na(+) and Ca(2+) channels but dependent on presynaptic [Ca(2+)](i). The increase of inhibitory synaptic transmission in response to acute bilirubin is a novel effect of bilirubin on the central nervous system and may have implications for neurotoxicity and the impairment of auditory transduction seen in hyperbilirubinemia.