The effects of venovenous bypass use in liver transplantation with piggyback technique: a propensity score-weighted analysis.

Venovenous bypass (VVB) use during liver transplantation (LT) is notably variable among the centres and it is actually restricted to surgically complex cases, severely unstable recipients or grafts from high-risk donors. Historically, VVB was associated with the classical LT with caval cross clamping, while not much is known about the safety of this technique applied to piggyback LT. This retrospective observational study evaluated the effects of VVB applied to piggyback LT on mortality, hospital outcomes, postoperative graft and other organ dysfunction. We retrospectively collected data about recipient status, surgical complexity and graft quality of all the piggyback LTs performed at the Transplant Unit of IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy, from January 2012 to December 2022. A propensity score (PS) was built taking into account the variables possibly associated with either VVB choice and the investigated outcomes with the average treatment overlap method. PS-weighted general linear models (GLMs) were developed to investigate the adjusted effect of VVB use on the selected outcomes. The final analysis included 874 LT cases, of whom 74 (8.5%) underwent VVB. The effective sample sizes after PS-weighting were 280.2 and 64.3 patients in the no-VVB and VVB groups, respectively. PS-weighted GLMs did not show any differences regarding hospital and graft-related outcomes. However, significantly higher odds ratios for serum creatinine > 2 mg/dL and AKIN stage 2 or 3 during the first 24 h after ICU admission together with a higher renal replacement therapy need during ICU stay were reported for VVB exposure in the weighted analyses. This study suggests similar mortality and length of stay but a higher risk for postoperative acute kidney injury in patients undergoing piggyback LT with VVB.

Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products.

Covering: 1995 to 2023Advances in bioanalytical methods, particularly mass spectrometry, have provided valuable molecular insights into the mechanisms of life. Non-targeted metabolomics aims to detect and (relatively) quantify all observable small molecules present in a biological system. By comparing small molecule abundances between different conditions or timepoints in a biological system, researchers can generate new hypotheses and begin to understand causes of observed phenotypes. Functional metabolomics aims to investigate the functional roles of metabolites at the scale of the metabolome. However, most functional metabolomics studies rely on indirect measurements and correlation analyses, which leads to ambiguity in the precise definition of functional metabolomics. In contrast, the field of natural products has a history of identifying the structures and bioactivities of primary and specialized metabolites. Here, we propose to expand and reframe functional metabolomics by integrating concepts from the fields of natural products and chemical biology. We highlight emerging functional metabolomics approaches that shift the focus from correlation to physical interactions, and we discuss how this allows researchers to uncover causal relationships between molecules and phenotypes.

How to use the Contour intrasaccular device: two illustrative cases.

Contour (Stryker, Kalamazoo, MI) is a relatively new endosaccular device for the treatment of intracranial aneurysms.1 2 Its unique cup-like shape permits treatment of most lesions, including wide-necked, irregular, and shallowed-shaped aneurysms. The sizing of the device only requires two parameters: neck size and equatorial plane (width). It must be positioned at the neck of the aneurysm with the device proximal marker in the parent artery. In our experience, dual antiplatelet therapy is usually not required for intrasaccular devices and this is also an advantage of the Contour device. We report two illustrative cases of wide-neck aneurysms in the anterior and posterior circulation, respectively (video 1). In this video we demonstrate the feasibility of this treatment in a middle cerebral artery bifurcation with atypical triangular shape and typical tip-basilar aneurysm. neurintsurg;16/3/225/V1F1V1Video 1 .

Trends in liver transplantation for primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated. AIM: We performed a national survey to investigate the listing criteria, comorbidities, and outcomes. METHODS: In April 2022, we surveyed liver transplantation in primary sclerosing cholangitis nationwide for the last 15 years. RESULTS: From 2007 to 2021, 445 patients were included on waiting lists, and 411 had undergone liver transplants. The median age at transplantation was 46 years (males 63.9%); 262 patients (59%) presented an inflammatory bowel disease. Transplants increased over the years, from 1.8 % in 2007 to 3.0 % in 2021. Cholangitis (51%) and hepatic decompensation (45%) were the main indications for listing. The disease recurred in 81 patients (20%). Patient survival after the first transplant was 94 %, 86% and 84% at one, five, and ten years. Twenty-four died in the first year (50% surgical complications, 25% infections); 33 between one to five years (36% recurrence, 21% cholangiocarcinoma recurrence) and nine after five years (56% de novo cancer, 44% recurrence). CONCLUSIONS: Primary sclerosing cholangitis has been an increasing indication for transplantation in Italy. Cholangitis and decompensation were the main indications for listing. Recurrence and cancer were the leading causes of death.

Defining the optimal size of an aspiration catheter in relation to the arterial diameter during mechanical thrombectomy for stroke.

BACKGROUND: Mechanical thrombectomy for acute ischemic stroke is effective and includes different technical approaches. Operators use direct aspiration, a stent retriever, or a combination of both. Direct aspiration can be performed with various catheters of different sizes depending on the diameter of the occluded vessel. PURPOSE: We studied the relationship between the catheter diameter in regards to the occluded vessel diameter and the rate of successful recanalization. MATERIALS AND METHODS: We conducted a retrospective, monocentric study on a series of consecutive patients treated with mechanical thrombectomy. For each procedure, we extracted each attempt that used direct aspiration and rated the attempt as successful or unsuccessful. We also measured the occluded artery diameter and calculated the ratio between the occluded artery and the aspiration catheter diameters. We tested the association between the diameter ratio and the recanalization status. We also performed inter-rater agreement for the arterial diameter measurement between three interventional neuroradiologists. RESULTS: We included 119 patients with 201 attempts of direct aspiration. A higher diameter ratio was associated with a higher recanalization rate. The analysis in terciles showed that the odds of success were 4.80 higher when the ratio was >0.71 vs <0.54 (p < 0.01). Inter-rater agreement showed near-perfect intraclass correlation with 0.93 (0.91-0.94) consistency and 0.92 (0.90-0.94) absolute agreement. CONCLUSIONS: We demonstrated an association between higher recanalization and a diameter of ratio >0.71 between the aspiration catheter and the occluded artery. These results could guide intraoperative decisions regarding the appropriate selection of aspiration catheters during mechanical thrombectomy increasing the rate of successful recanalisation. A larger study could provide additional data to further specify the optimal ratio.

Alpha-Lipoic Acid Reduces Cell Growth, Inhibits Autophagy, and Counteracts Prostate Cancer Cell Migration and Invasion: Evidence from In Vitro Studies.

Alpha-lipoic acid (ALA) is a natural antioxidant dithiol compound, exerting antiproliferative and antimetastatic effects in various cancer cell lines. In our study, we demonstrated that ALA reduces the cell growth of prostate cancer cells LNCaP and DU-145. Western blot results revealed that in both cancer cells, ALA, by upregulating pmTOR expression, reduced the protein content of two autophagy initiation markers, Beclin-1 and MAPLC3. Concomitantly, MTT assays showed that chloroquine (CQ) exposure, a well-known autophagy inhibitor, reduced cells' viability. This was more evident for treatment using the combination ALA + CQ, suggesting that ALA can reduce cells' viability by inhibiting autophagy. In addition, in DU-145 cells we observed that ALA affected the oxidative/redox balance system by deregulating the KEAP1/Nrf2/p62 signaling pathway. ALA decreased ROS production, SOD1 and GSTP1 protein expression, and significantly reduced the cytosolic and nuclear content of the transcription factor Nrf2, concomitantly downregulating p62, suggesting that ALA disrupted p62-Nrf2 feedback loop. Conversely, in LNCaP cells, ALA exposure upregulated both SOD1 and p62 protein expression, but did not affect the KEAP1/Nrf2/p62 signaling pathway. In addition, wound-healing, Western blot, and immunofluorescence assays evidenced that ALA significantly reduced the motility of LNCaP and DU-145 cells and downregulated the protein expression of TGFß1 and vimentin and the deposition of fibronectin. Finally, a soft agar assay revealed that ALA decreased the colony formation of both the prostate cancer cells by affecting the anchorage independent growth. Collectively, our in vitro evidence demonstrated that in prostate cancer cells, ALA reduces cell growth and counteracts both migration and invasion. Further studies are needed in order to achieve a better understanding of the underlined molecular mechanisms.

The Evolving Landscape of Therapeutics for Epilepsy in Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder characterized by benign tumor growth in multiple organs, including the brain, kidneys, heart, eyes, lungs, and skin. Pathogenesis stems from mutations in either the TSC1 or TSC2 gene, which encode the proteins hamartin and tuberin, respectively. These proteins form a complex that inhibits the mTOR pathway, a critical regulator of cell growth and proliferation. Disruption of the tuberin-hamartin complex leads to overactivation of mTOR signaling and uncontrolled cell growth, resulting in hamartoma formation. Neurological manifestations are common in TSC, with epilepsy developing in up to 90% of patients. Seizures tend to be refractory to medical treatment with anti-seizure medications. Infantile spasms and focal seizures are the predominant seizure types, often arising in early childhood. Drug-resistant epilepsy contributes significantly to morbidity and mortality. This review provides a comprehensive overview of the current state of knowledge regarding the pathogenesis, clinical manifestations, and treatment approaches for epilepsy and other neurological features of TSC. While narrative reviews on TSC exist, this review uniquely synthesizes key advancements across the areas of TSC neuropathology, conventional and emerging pharmacological therapies, and targeted treatments. The review is narrative in nature, without any date restrictions, and summarizes the most relevant literature on the neurological aspects and management of TSC. By consolidating the current understanding of TSC neurobiology and evidence-based treatment strategies, this review provides an invaluable reference that highlights progress made while also emphasizing areas requiring further research to optimize care and outcomes for TSC patients.

Antitumor Activity of Axitinib in Lung Carcinoids: A Preclinical Study.

Lung carcinoids (LCs) comprise well-differentiated neuroendocrine tumors classified as typical (TCs) and atypical (ACs) carcinoids. Unfortunately, curative therapies remain elusive for metastatic LCs, which account for 25-30% of cases. This study evaluated the antitumor activity of axitinib (AXI), a second-generation tyrosine kinase inhibitor selectively targeting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3) in human lung TC (NCI-H727, UMC-11, NCI-H835) and AC (NCI-H720) cell lines. In vitro and in vivo (zebrafish) assays were performed following AXI treatment to gather several read-outs about cell viability, cell cycle, the secretion of proangiogenic factors, apoptosis, tumor-induced angiogenesis and migration. AXI demonstrated relevant antitumor activity in human LC cells, with pronounced effects observed in UMC-11 and NCI-H720, characterized by cell cycle perturbation and apoptosis induction. AXI significantly hindered tumor induced-angiogenesis in Tg(fli1a:EGFP)y1 zebrafish embryos implanted with all LC cell lines and also reduced the invasiveness of NCI-H720 cells, as well as the secretion of several proangiogenic factors. In conclusion, our study provides initial evidence supporting the potential anti-tumor activity of AXI in LC, offering a promising basis for future investigations in mammalian animal models and, eventually, progressing to clinical trials.

Cabozantinib in neuroendocrine tumors: tackling drug activity and resistance mechanisms.

Neuroendocrine tumors (NETs) are highly vascularized malignancies in which angiogenesis may entail cell proliferation and survival. Among the emerging compounds with antivascular properties, cabozantinib (CAB) appeared promising. We analyzed the antitumor activity of CAB against NETs utilizing in vitro and in vivo models. For cell cultures, we used BON-1, NCI-H727 and NCI-H720 cell lines. Cell viability was assessed by manual count coupled with quantification of cell death, performed through fluorescence-activated cell sorting analysis as propidium iodide exclusion assay. In addition, we investigated the modulation of the antiapoptotic myeloid cell leukemia 1 protein under CAB exposure, as a putative adaptive pro-survival mechanism, and compared the responses with sunitinib. The activity of CAB was also tested in mouse and zebrafish xenograft tumor models. Cabozantinib showed a dose-dependent and time-dependent effect on cell viability and proliferation in human NET cultures, besides a halting of cell cycle progression for endoduplication, never reported for other tyrosine kinase inhibitors. In a transplantable zebrafish model, CAB drastically inhibited NET-induced angiogenesis and migration of implanted cells through the embryo body. CAB showed encouraging activity in NETs, both in vitro and in vivo models. On this basis, we envisage future research to further investigate along these promising lines.

The influence of inflammation and frailty in the aging continuum.

Inflammaging is a low-grade inflammatory state that can be considered an adaptive process aimed at stimulating appropriate anti-inflammatory response. Frailty is determined by the accumulation of molecular and cellular defects accumulated throughout life; therefore, an appropriate frailty computation could be a valuable tool for measuring biological age. This study aims to analyse the association between inflammatory markers and both chronological age "per se" and frailty. We studied 452 persons aged 43-114 years. A Frailty Index (FI) was computed considering a wide range of age-related signs, symptoms, disabilities, and diseases. Plasma concentrations of inflammatory cytokines and peripheral markers of neuroinflammation were analysed by next-generation ELISA. The mean age of the cohort was 79.7 (from 43 to 114) years and the median FI was 0.19 (from 0.00 to 0.75). The concentrations of most inflammatory markers increased significantly with chronological age, after adjustment for sex and FI. Interferon-γ was significantly affected only by FI, while interleukin (IL)-10 and IL-1ß were associated only with chronological age. In conclusion, we described different associations between inflammatory components and chronological vs. biological age. A better characterization of the molecular signature of aging could help to understand the complexity of this process.

Reverse Mirizzi Syndrome.

A man in his 40s presented to our Hospital with abdominal pain, jaundice, and pruritus. He had a history of Alagille Syndrome treated with cholecystojejunostomy in the neonatal period because of initial misdiagnosis of biliary atresia. Laboratory investigations showed hyperbilirubinemia (total bilirubin 1.76 mg/dL [<1.2 mg/dL]; conjugated 1.06 mg/dL [<0.3 mg/dL]) and cholestasis (GGT 78 U/L [<50 U/L]; ALP 200 U/L [<50 U/L]). Transabdominal ultrasound was limited by aerobilia due to the cholecystojejuno-anastomosis. Subsequent basal CT scan revealed an impacted stone within the patient's native common bile duct (CBD). Aerobilia in intrahepatic bile ducts and gallbladder was reported. Magnetic Resonance cholangiopancreatography confirmed the gallstone in the CBD compressing cystic duct and common hepatic duct, with dilation of the upstream bile ducts. Furthermore, the native CBD was obstructed by other gallstones. In Mirizzi syndrome, gallstones impacted in gallbladder's Hartmann's pouch or cystic duct extrinsically compress CBD. We suggest naming the present condition "Reverse Mirizzi Syndrome" (Renzulli Matteo Syndrome, RMS) because it is the exact opposite of Mirizzi syndrome.

Capmatinib-Induced Liver Injury as Emerging Toxicity of MET Inhibitors in Patients With NSCLC Pretreated With Immune Checkpoint Inhibitors.

Safety data on MET inhibitors in patients with advanced NSCLC harboring MET exon 14 mutation and treated with frontline immune checkpoint inhibitors (ICIs) are still limited. Here, we describe clinical characteristics, liver biopsy features, and management of liver injury of two patients with a diagnosis of MET exon 14-mutant NSCLC receiving capmatinib after ICI failure. On the basis of histologic findings and exclusion of other potential causes, a diagnosis of drug-induced liver injury (DILI) associated with portal fibrosis was made in both cases. The use of hepatoprotective drugs, in addition to oral ursodeoxycholic acid, resulted in liver blood tests normalization. To provide a global safety perspective, we queried the Food and Drug Administration Adverse Event Reporting System and detected a robust disproportionality signal. Out of the 918 total reports with capmatinib from the Food and Drug Administration Adverse Event Reporting System database, DILI was recorded in 43 cases (4.7%), mostly serious (93.0%) with hospitalization and death recorded in 25.6% and 16.3% of the cases, respectively. The median time to onset was 42 days, with discontinuation and positive dechallenge documented in 41.9% and 39.5% of the cases, respectively. Anti-programmed cell death protein-1 agents were coreported in 11 DILI cases. Only two cases of DILI out of 105 reports were found for tepotinib. Our data support a potential association between capmatinib and DILI in patients who have also been previously exposed to immunotherapy. Considering the potential implications for sequence strategy and timing of ICI and MET inhibitor, further investigation is warranted.

Polycystic ovary syndrome and thyroid disorder: a comprehensive narrative review of the literature.

Background: Published data on the relationship between polycystic ovary syndrome (PCOS) and thyroid dysfunction are sparse and confusing. Objective: To comprehensively review data available in the literature regarding the relationship between PCOS and the thyroid function, and its abnormalities. Methods: Nine main areas of interest were identified and analyzed according to the available evidence: 1) Evaluation of thyroid function for PCOS diagnosis; 2) Epidemiology data on thyroid function/disorders in patients with PCOS, and vice versa; 3) Experimental data supporting the relationship between thyroid function/disorders and PCOS; 4) Effects of thyroid function/disorders on PCOS features, and vice versa; 5) Effect of thyroid alterations on the cardiometabolic risk in women with PCOS; 6) Effect of thyroid abnormalities on reproductive outcomes in women with PCOS; 7) Relationship between thyroid function/abnormalities in patients with PCOS who are undergoing fertility treatment; 8) Effect of treatments for thyroid diseases on PCOS; and 9) Effect of treatments for PCOS on thyroid function. An extensive literature search for specific keywords was performed for articles published from 1970 to March 2023 using PubMed and Web of Science. Data were reported in a narrative fashion. Results: PCOS is a diagnosis of exclusion for which diagnosis is possible only after excluding disorders that mimic the PCOS phenotype, including thyroid dysfunctions. However, the tests and the cutoff values used for this are not specified. Many experimental and clinical data suggest a relationship between perturbations of the thyroid function and PCOS. Direct and unequivocal evidence on the effects of thyroid function/disorders on PCOS features are lacking. High thyroid-stimulating hormone levels and subclinical hypothyroidism may be associated with significant worsening of several intermediate endpoints of cardiometabolic risk in women with PCOS. Thyroid abnormalities may worsen reproductive outcomes, especially in patients undergoing fertility treatment. To date, there are no data demonstrating the efficacy of thyroid medications on fertility and cardiometabolic risk in women with PCOS. Lifestyle modification changes, metformin, and vitamin D seem to improve thyroid function in the general population. Conclusion: PCOS and thyroid disorders are closely related, and their coexistence may identify patients with a higher reproductive and metabolic risk. Regular screening for thyroid function and thyroid-specific autoantibodies in women with PCOS, particularly before and during pregnancy, is highly recommended.

A metabologenomics approach to unlock the metabolome of the novel Antarctic deep-sea isolate Lacinutrix shetlandiensis sp. nov. WUR7.

The South Shetland Trough, Antarctica, is an underexplored region for microbiological and biotechnological exploitation. Herein, we describe the isolation and characterization of the novel bacterium Lacinutrix shetlandiensis sp. nov. WUR7 from a deep-sea environment. We explored its chemical diversity via a metabologenomics approach, wherein the OSMAC strategy was strategically employed to upregulate cryptic genes for secondary metabolite production. Based on hybrid de novo whole genome sequencing and digital DNA-DNA hybridization, isolate WUR7 was identified as a novel species from the Gram-negative genus Lacinutrix. Its genome was mined for the presence of biosynthetic gene clusters with limited results. However, extensive investigation of its metabolism uncovered an unusual tryptophan decarboxylase with high sequence homology and conserved structure of the active site as compared to ZP_02040762, a highly specific tryptophan decarboxylase from Ruminococcus gnavus. Therefore, WUR7's metabolism was directed toward indole-based alkaloid biosynthesis by feeding it with L-tryptophan. As expected, its metabolome profile changed dramatically, by triggering the extracellular accumulation of a massive array of metabolites unexpressed in the absence of tryptophan. Untargeted LC-MS/MS coupled with molecular networking, followed along with chemoinformatic dereplication, allowed for the annotation of 10 indole alkaloids, belonging to ß-carboline, bisindole, and monoindole classes, alongside several unknown alkaloids. These findings guided us to the isolation of a new natural bisindole alkaloid 8,9-dihydrocoscinamide B (1), as the first alkaloid from the genus Lacinutrix, whose structure was elucidated on the basis of extensive 1D and 2D NMR and HR-ESIMS experiments. This comprehensive strategy allowed us to unlock the previously unexploited metabolome of L. shetlandiensis sp. nov. WUR7.

Transesophageal Echocardiography Guidance to Prevent and Manage Pitfalls from Abdominal Normothermic Regional Perfusion and Optimize Timing during Organ Retrieval from a Donor after Circulatory Death.

An essential means of collecting more abdominal donor organs is controlled donation after circulatory death (cDCD). The organs are typically preserved during cDCD using the abdominal normothermic regional perfusion (A-NRP) technique to recirculate oxygenated blood flow following cardiac arrest and the withdrawal of life support. One of the challenges of A-NRP is ensuring the correct vascular devices' positionings, specifically extracorporeal membrane oxygenation cannulae and aortic balloons, typically achieved through fluoroscopy with or without contrast agents. Here, we present a case report in which transesophageal echocardiography (TEE) helped the transplant team to effectively procure viable abdominal organs from a cDCD donor in the shortest time frame, as minimizing time is one of the most crucial factors in maintaining organ viability. TEE use leads to a more effective and efficient A-NRP procedure with limited complications. In addition, it allows us to observe the circulation of both the thoracic and part of the abdominal organs using one fast exam. This case is the first report describing TEE as a primary guide and useful tool for DCD donors. However, prospective studies are needed to confirm that TEE could be used as standard practice during all DCD organ retrieval procedures.

Adherence to Mediterranean diet in liver transplant recipients: a cross-sectional multicenter study.

BACKGROUND: Seeing the importance of healthy diet after liver transplant (LT), our study aimed to evaluate the adherence to Mediterranean diet (MD) in a large population of LT recipients. METHODS: The present multicenter study was developed in clinically stable, liver transplanted patients, from June to September 2021. Patients completed a survey about adherence to MD, Quality of Life (QoL), sport, and employment. To analyze the correlations, we computed Pearson's coefficients; while to compare subgroups, independent samples t-tests and ANOVAs. We used a multivariable logistic regression analysis to find the predictors of impaired adherence to MD. RESULTS: The questionnaire was administered to 511 patients. They were males in 71% of cases with a mean age of 63.1 years (SD±10.8). LT recipients coming from central Italy displayed higher adherence to the MD (M=11.10±1.91) than patients from northern (M=9.94±2.28, P<0.001) or southern Italy (M=10.04±2.16, P<0.001). Patients from central Italy showed a significantly higher consumption of fruit, vegetables, legumes, cereals, olive oil, fish and a significantly lower intake of dairy products than patients resident in the other Italian areas. At multivariate analysis, recipients from central Italy were 3.8 times more likely to report adherence to the MD. Patients with a high physical health score were more adherent to MD, as well as patients transplanted at an earlier time. CONCLUSIONS: We demonstrated that place of stay, time from transplant and physical dimension of QoL significantly influences the adherence to MD. Continuous information campaigns about a correct diet and lifestyle would be necessary.

Zebrafish dnm1a gene plays a role in the formation of axons and synapses in the nervous tissue.

Classical dynamins (DNMs) are GTPase proteins engaged in endocytosis, a fundamental process for cargo internalization from the plasma membrane. In mammals, three DNM genes are present with different expression patterns. DNM1 is expressed at high levels in neurons, where it takes place in the recycling of synaptic vesicles; DNM2 is ubiquitously expressed, while DNM3 is found in the brain and in the testis. Due to the conservation of genes in comparison to mammals, we took advantage of a zebrafish model for functional characterization of dnm1a, ortholog of mammalian DNM1. Our data strongly demonstrated that dnm1a has a nervous tissue-specific expression pattern and plays a role in the formation of both axon and synapse. This is the first in vivo study that collects evidence about the effects of dnm1a loss of function in zebrafish, thus providing a new excellent model to be used in different scientific fields.

Human Microglia Synthesize Neurosteroids to Cope with Rotenone-Induced Oxidative Stress.

We obtained evidence that mouse BV2 microglia synthesize neurosteroids dynamically to modify neurosteroid levels in response to oxidative damage caused by rotenone. Here, we evaluated whether neurosteroids could be produced and altered in response to rotenone by the human microglial clone 3 (HMC3) cell line. To this aim, HMC3 cultures were exposed to rotenone (100 nM) and neurosteroids were measured in the culture medium by liquid chromatography with tandem mass spectrometry. Microglia reactivity was evaluated by measuring interleukin 6 (IL-6) levels, whereas cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. After 24 h (h), rotenone increased IL-6 and reactive oxygen species levels by approximately +37% over the baseline, without affecting cell viability; however, microglia viability was significantly reduced at 48 h (p < 0.01). These changes were accompanied by the downregulation of several neurosteroids, including pregnenolone, pregnenolone sulfate, 5α-dihydroprogesterone, and pregnanolone, except for allopregnanolone, which instead was remarkably increased (p < 0.05). Interestingly, treatment with exogenous allopregnanolone (1 nM) efficiently prevented the reduction in HMC3 cell viability. In conclusion, this is the first evidence that human microglia can produce allopregnanolone and that this neurosteroid is increasingly released in response to oxidative stress, to tentatively support the microglia's survival.