Postoperative Cognitive Impairment and Pain Perception after Abdominal Surgery-Could Immersive Virtual Reality Bring More? A Clinical Approach.

Background and Objectives: Impaired cognition and pain after surgery contribute to prolonged hospital stays and increased mortality rates. Thus, the development of preemptive algorithms for reducing their impact should be prioritized. The main objectives of the present study were to evaluate the efficiency of using virtual reality (VR) to treat postoperative cognitive decline and pain perception. Materials and Methods: The study was a prospective, monocentric, clinical study that included 51 patients who have undergone major abdominal surgery. The patients were divided into two groups: Control (n = 25) and VR (n = 26). The VR sessions consisted of 5-8 min exposure at 24-48 h after surgery. We considered the outcome variables, the mini-mental state examination, and visual analogue scale at 24-48 h after surgery. The dependent variables were age, social status, educational level, and duration of surgery. Results: We did not observe any differences in postoperative cognition deficit with regard to VR. The VR, however, successfully reduced postoperative pain intensity. Moreover, the patients' age, surgery duration, level of education, and social status influenced the MMSE score at 24-48 h after surgery. Conclusions: Even if using VR does not alleviate short-term postoperative cognitive impairments, it could affect pain perception. Further studies are needed to support the use of VR in perioperative contexts.

Acute Promyelocytic Leukemia and Severe Differentiation Syndrome in Pregnancy-A Management Challenge.

Acute promyelocytic leukemia (APL) is generated by the PML-RARA fusion gene. In patients suffering from APL, the early diagnosis and treatment are essential in the successful management. We reported a case of a 27-year-old 17th-week pregnant patient diagnosed with APL. After an extensive hematological diagnostic panel, the acute promyelocytic leukemia was confirmed, and the patient received all-trans retinoic acid (ATRA), idarubicin (IDA), and dexamethasone, following national guidelines. Due to ATRA-related differentiation syndrome, the therapy was adjusted, and hydroxycarbamide was added with a good outcome. The patient was admitted to the ICU secondary to hypoxemic respiratory failure on the 2nd day after hospital admission. Our patient received an individualized drug combination, adjusted by the clinical response. Furthermore, the drugs used in APL treatment are all teratogenic. Despite various major complications, including severe acute respiratory distress syndrome (ARDS), which needed mechanical ventilation; ICU-acquired myopathy; and spontaneous abortion, the patient had a good outcome and was transferred from the ICU after a total stay of 40 days. APL during pregnancy is a rare entity of intermediate-risk APL. Our study emphasized the need for individualized therapy in a rare case of a pregnant woman diagnosed with a potentially fatal hematologic disease.

Orthotopic Liver Transplantation of a SARS-CoV-2 Negative Recipient from a Positive Donor: The Border between Uncertainty and Necessity in a Pandemic Era- Case Report and Overview of the Literature.

(1) Introduction: Liver transplantation represents the gold-standard therapy in eligible patients with acute liver failure or end-stage liver disease. The COVID-19 pandemic dramatically affected the transplantation landscape by reducing patients' addressability to specialized healthcare facilities. Since evidence-based acceptance guidelines for non-lung solid organ transplantation from SARS-CoV-2 positive donors are lacking, and the risk of bloodstream-related transmission of the disease is debatable, liver transplantation from SARS-CoV-2 positive donors could be lifesaving, even if long-term interactions are unpredictable. The aim of this case report is to highlight the relevance of performing liver transplantation from SARS-CoV-2 positive donors to negative recipients by emphasizing the perioperative care and short-term outcome. (2) Case presentation: A 20-year-old female patient underwent orthotropic liver transplantation for Child-Pugh C liver cirrhosis secondary to overlap syndrome, from a SARS-CoV-2 positive brain death donor. The patient was not infected nor vaccinated against SARS-CoV-2, and the titer of neutralizing antibodies against the spike protein was negative. The liver transplantation was performed with no significant complications. As immunosuppression therapy, the patient received 20 mg basiliximab (Novartis Farmacéutica S.A., Barcelona, Spain) and 500 mg methylprednisolone (Pfizer Manufacturing Belgium N.V, Puurs, Belgium) intraoperatively. Considering the risk of non-aerogene-related SARS-CoV-2 reactivation syndrome, the patient received remdesivir 200 mg (Gilead Sciences Ireland UC, Carrigtohill County Cork, Ireland) in the neo-hepatic stage, which was continued with 100 mg/day for 5 days. The postoperative immunosuppression therapy consisted of tacrolimus (Astellas Ireland Co., Ltd., Killorglin, County Kerry, Ireland) and mycophenolate mofetil (Roche România S.R.L, Bucharest, Romania) according to the local protocol. Despite the persistent negative PCR results for SARS-CoV-2 in the upper airway tract, the blood titer of neutralizing antibodies turned out positive on postoperative day 7. The patient had a favorable outcome, and she was discharged from the ICU facility seven days later. (3) Conclusions: We illustrated a case of liver transplantation of a SARS-CoV-2 negative recipient, whose donor was SARS-CoV-2 positive, performed in a tertiary, university-affiliated national center of liver surgery, with a good outcome, in order to raise the medical community awareness on the acceptance limits in the case of COVID-19 incompatibility for non-lung solid organs transplantation procedures.

The Management of Postoperative Cognitive Dysfunction in Cirrhotic Patients: An Overview of the Literature.

Background and objectives: Postoperative cognitive dysfunction (POCD) represents a decreased cognitive performance in patients undergoing general anesthesia for major surgery. Since liver cirrhosis is associated with high mortality and morbidity rates, cirrhotic patients also assemble many risk factors for POCD. Therefore, preserving cognition after major surgery is a priority, especially in this group of patients. The purpose of this review is to summarize the current knowledge regarding the effectiveness of perioperative therapeutic strategies in terms of cognitive dysfunction reduction. Data Collection: Using medical search engines such as PubMed, Google Scholar, and Cochrane library, we analyzed articles on topics such as: POCD, perioperative management in patients with cirrhosis, hepatic encephalopathy, general anesthesia in patients with liver cirrhosis, depth of anesthesia, virtual reality in perioperative settings. We included 115 relevant original articles, reviews and meta-analyses, and other article types such as case reports, guidelines, editorials, and medical books. Results: According to the reviewed literature, the predictive capacity of the common clinical tools used to quantify cognitive dysfunction in cirrhotic settings is reduced in perioperative settings; however, novel neuropsychological tools could manage to better identify the subclinical forms of perioperative cognitive impairments in cirrhotic patients. Moreover, patients with preoperative hepatic encephalopathy could benefit from specific preventive strategies aimed to reduce the risk of further neurocognitive deterioration. Intraoperatively, the adequate monitoring of the anesthesia depth, appropriate anesthetics use, and an opioid-sparing technique have shown favorable results in terms of POCD. Early recovery after surgery (ERAS) protocols should be implemented in the postoperative setting. Other pharmacological strategies provided conflicting results in reducing POCD in cirrhotic patients. Conclusions: The perioperative management of the cognitive function of cirrhotic patients is challenging for anesthesia providers, with specific and targeted therapies for POCD still sparse. Therefore, the implementation of preventive strategies appears to remain the optimal attitude. Further research is needed for a better understanding of POCD, especially in cirrhotic patients.

Toxic-Induced Nonthyroidal Illness Syndrome Induced by Acute Low-Dose Pesticides Exposure-Preliminary In Vivo Study.

BACKGROUND AND OBJECTIVES: Conditions such as trauma, burns, sepsis, or acute intoxications have considerable consequences on the endocrine status, causing "sick euthyroid syndrome". Organophosphate exposure may induce an increase in acetylcholine levels, thus altering the thyroid's hormonal status. The present study aims to identify the effects of acetylcholinesterase inhibition on thyroid hormones. MATERIAL AND METHODS: A prospective experimental study was conducted on twenty Wistar rats. Blood samples were drawn to set baseline values for thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). Chlorpyrifos 0.1 mg/kg was administered by oral gavage to induce acetyl-cholinesterase inhibition. After exhibiting cholinergic symptoms, blood samples were collected to assess levels of cholinesterase and thyroid hormones using ELISA. RESULTS: Butyrylcholinesterase levels confirmed major inhibition immediately after intoxication compared to the baseline, certifying the intoxication. A significant increase in T4 levels was noted (p = 0.01) both at 2 h and 48 h after administration of organophosphate in sample rats. Similarly, T3 almost doubled its value 2 h after poisoning (4.2 ng/mL versus 2.5 ng/mL at baseline). Surprisingly, TSH displayed acute elevation with an afterward slow descending trend at 48 h (p = 0.1), reaching baseline value. CONCLUSIONS: This study demonstrated that cholinesterase inhibition caused major alterations in thyroid hormone levels, which may be characterized by a transient hypothyroidism status with an impact on survival prognosis.

Mesenteric Ischemia in a Patient with Essential Thrombocythemia: Does COVID-19 Play Any Role? A Case Report and Overview of the Literature.

INTRODUCTION: Chronic mesenteric ischemia is a rare entity with non-specific symptomatology; combined with rare etiologies, it could lead to unwarranted surgical indication. CASE REPORT: We report the case of an 85-year-old woman, with a history of hypertension, persistent thrombocytosis, atherosclerosis, and recent minor COVID-19 infection, presenting to the hospital with postprandial abdominal pain and nonspecific clinical examination findings; upon abdominal CT, superior mesenteric artery circumferential thrombosis was revealed. A bone marrow biopsy was performed due to suspected essential thrombocythemia, confirming the diagnosis. An endovascular approach was chosen as therapy option and a stent was placed in the occluded area. Dual antiplatelet and cytoreductive therapies were initiated after the intervention. Clinical course was excellent, with no residual stenosis 1 month after stenting. CONCLUSIONS: The therapeutic strategy in elderly patients with exacerbated chronic mesenteric ischemia requires an interdisciplinary approach in solving both the exacerbation and the underlying conditions in order to prevent further thrombotic events. Although the patient presented a thrombotic state, other specific risk factors such as COVID-19 related-coagulopathy and essential thrombocythemia should be considered.

What Is Different in Acute Hematologic Malignancy-Associated ARDS? An Overview of the Literature.

Background and Objectives: Acute hematologic malignancies are a group of heterogeneous blood diseases with a high mortality rate, mostly due to acute respiratory failure (ARF). Acute respiratory distress syndrome (ARDS) is one form of ARF which represents a challenging clinical condition. The paper aims to review current knowledge regarding the variable pathogenic mechanisms, as well as therapeutic options for ARDS in acute hematologic malignancy patients. Data collection: We provide an overview of ARDS in patients with acute hematologic malignancy, from an etiologic perspective. We searched databases such as PubMed or Google Scholar, including articles published until June 2022, using the following keywords: ARDS in hematologic malignancy, pneumonia in hematologic malignancy, drug-induced ARDS, leukostasis, pulmonary leukemic infiltration, pulmonary lysis syndrome, engraftment syndrome, diffuse alveolar hemorrhage, TRALI in hematologic malignancy, hematopoietic stem cell transplant ARDS, radiation pneumonitis. We included relevant research articles, case reports, and reviews published in the last 18 years. Results: The main causes of ARDS in acute hematologic malignancy are: pneumonia-associated ARDS, leukostasis, leukemic infiltration of the lung, pulmonary lysis syndrome, drug-induced ARDS, radiotherapy-induced ARDS, diffuse alveolar hemorrhage, peri-engraftment respiratory distress syndrome, hematopoietic stem cell transplantation-related ARDS, transfusion-related acute lung injury. Conclusions: The short-term prognosis of ARDS in acute hematologic malignancy relies on prompt diagnosis and treatment. Due to its etiological heterogeneity, precision-based strategies should be used to improve overall survival. Future studies should focus on identifying the relevance of such etiologic-based diagnostic strategies in ARDS secondary to acute hematologic malignancy.

The Outcome of Surgical Treatment for the Neuropathic Diabetic Foot Lesions-A Single-Center Study.

The prevalence of diabetic foot complications is continuously increasing as diabetes has become one of the most important "epidemics" of our time. The main objective of this study was to describe the appropriate surgical intervention for the complicated neuropathic diabetic foot; the secondary goal was to find the risk factors associated with minor/major amputation and good or adverse surgical outcomes. This is an observational, retrospective study conducted between 1 January 2018 and 31 December 2019, which included 251 patients from the General Surgery Department at the Dr I. Cantacuzino Clinical Hospital in Bucharest with type II diabetes mellitus and neuropathic diabetic foot complications. The surgical conditions identified at admission were the following: osteitis (38.6%), infected foot ulcer (27.5%), gangrene (20.7%), infected Charcot foot (3.6%), non-healing wound (3.6%), necrosis (3.2%), and granulated wound (2.8%). We found that a minor surgical procedure (transmetatarsal amputation of the toe and debridement) was performed in 85.8% of cases, and only 14.2% needed major amputations. Osteitis was mainly associated with minor surgery (p = 0.001), while the gangrene and the infected Charcot foot were predictable for major amputation, with OR = 2.230, 95% CI (1.024-4.857) and OR = 5.316, 95% CI (1.354-20.877), respectively. Admission anemia and diabetic nephropathy were predictive of a major therapeutical approach, with p = 0.011, OR = 2.975, 95% CI (1.244-8.116) and p = 0.001, OR = 3.565, 95% CI (1.623-7.832), respectively. All the major amputations had a good outcome, while only several minor surgeries were interpreted as the adverse outcome (n = 24). Osteitis (45.8%) and admission anemia (79.2%) were more frequently associated with adverse outcomes, with p = 0.447 and p = 0.054, respectively. The complicated neuropathic diabetic foot requires a surgical procedure mainly associated with a good outcome.

Anti-MDA5 Amyopathic Dermatomyositis-A Diagnostic and Therapeutic Challenge.

Clinically amyopathic Dermatomyositis (CADM) is a rare subtype of idiopathic inflammatory myositis, associated with no muscular manifestations, which is more frequent in Asian women. Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are a recently discovered type of specific autoantibodies associated with myositis. The anti-MDA5 DM was initially described in Japan and later it was discovered that the target antigen was a protein implicated in the innate immune response against viruses, that is encoded by the melanoma differentiation-associated gene 5. Anti-MDA5 DM is characteristically associated with distinguished mucocutaneus and systemic manifestations, including skin ulcerations, palmar papules, arthritis, and interstitial-lung disease. Patients with anti-MDA5 positivity have a high risk of developing rapid progressive interstitial-lung disease (RP-ILD), with a poor outcome. As a result, despite high mortality, diagnosis is often delayed, necessitating increased awareness of this possible condition. Despite a severe course of lung disease and an increased mortality rate, there is currently no standard treatment. Recent insights based on observational studies and case reports support combined therapy with immunosuppressive drugs and corticotherapy, as soon as the symptoms appear. The aim of this paper is to describe anti-MDA5 DM, focusing on the recent literature about the unique clinical manifestations and therapeutic options, starting from a severe clinical case diagnosed in our Rheumatology Department.

Opioid-Sparing Analgesia Impacts the Perioperative Anesthetic Management in Major Abdominal Surgery.

Background and Objectives: The management of acute postoperative pain (APP) following major abdominal surgery implies various analgetic strategies. Opioids lie at the core of every analgesia protocol, despite their side effect profile. To limit patients' exposure to opioids, considerable effort has been made to define new opioid-sparing anesthesia techniques relying on multimodal analgesia. Our study aims to investigate the role of adjuvant multimodal analgesic agents, such as ketamine, lidocaine, and epidural analgesia in perioperative pain control, the incidence of postoperative cognitive dysfunction (POCD), and the incidence of postoperative nausea and vomiting (PONV) after major abdominal surgery. Materials and Methods: This is a clinical, observational, randomized, monocentric study, in which 80 patients were enrolled and divided into three groups: Standard group, C (n = 32), where patients received perioperative opioids combined with a fixed regimen of metamizole/acetaminophen for pain control; co-analgetic group, Co-A (n = 26), where, in addition to standard therapy, patients received perioperative systemic ketamine and lidocaine; and the epidural group, EA (n = 22), which included patients that received standard perioperative analgetic therapy combined with epidural analgesia. We considered the primary outcome, the postoperative pain intensity, assessed by the visual analogue scale (VAS) at 1 h, 6 h, and 12 h postoperatively. The secondary outcomes were the total intraoperative fentanyl dose, total postoperative morphine dose, maximal intraoperative sevoflurane concentration, confusion assessment method for intensive care units score (CAM-ICU) at 1 h, 6 h, and 12 h postoperatively, and the postoperative dose of ondansetron as a marker for postoperative nausea and vomiting (PONV) severity. Results: We observed a significant decrease in VAS score, as the primary outcome, for both multimodal analgesic regimens, as compared to the control. Moreover, the intraoperative fentanyl and postoperative morphine doses were, consequently, reduced. The maximal sevoflurane concentration and POCD were reduced by EA. No differences were observed between groups concerning PONV severity. Conclusions: Multimodal analgesia concepts should be individualized based on the patient's needs and consent. Efforts should be made to develop strategies that can aid in the reduction of opioid use in a perioperative setting and improve the standard of care.

Epigenetics in inflammatory liver diseases: A clinical perspective (Review).

Inflammatory liver diseases are, nowadays, multifactorial and wide-spread, thus having an important socio-economic impact. Although the therapeutic algorithms are well-known in hepatitis, regardless of etiology, strategies to identify inflammatory hepatic lesions in early stages and to develop new epigenetic therapies should be prioritized. The main entities of inflammatory liver disease are: alcoholic and non-alcoholic fatty liver disease, autoimmune hepatitis, viral hepatitis and Wilson disease. The main epigenetic processes include: DNA methylation/demethylation, which imply changes in DNA tertiary structure; post-translational histone covalent changes (methylation/demethylation, acetylation/deacetylation, ubiquitination), that cause DNA-histone instability; synthesis of small, non-coding RNA molecules, called microRNAs, that modulate translational potential of transcripts (mRNAs) and post-translational modification of polypeptide chains. Consequently, the epigenetic interactions aforementioned, play an important modulatory role in disease progression and response to conventional therapies The present review focused on the main epigenetic changes in inflammatory liver conditions, considering a new perspective: Epigenetic therapy. This approach is more than welcomed, taking into consideration that conventional therapeutic strategies are almost exhausted.

COVID-19 Pandemic Was Associated with Lower Activity but Not Higher Perioperative Mortality in a Large Eastern European Center.

BACKGROUND Surges of critically ill patients can overwhelm hospitals during pandemic waves and disrupt essential surgical activity. This study aimed to determine whether hospital mortality increased during the COVID-19 pandemic and during pandemic waves. MATERIAL AND METHODS This was a retrospective analysis of a prospective, observational, epidemiological database. All patients who underwent surgery from January 1 to December 31, 2020, were included in the analysis. The setting was a large Eastern European Surgical Center referral center of liver transplant and liver surgery, a major center of abdominal surgery. RESULTS A total of 1078 patients were analyzed, and this number corresponded to a reduction of surgical activity by 30% during the year 2020 compared with 2019. Despite an increase in surgery complexity during the pandemic, perioperative mortality was not different, and this was maintained during the pandemic wave. The pandemic (OR 1.45 [0.65-3.22], P=0.365) and the wave period (OR 0.897 [0.4-2], P=0.79) were not associated with hospital mortality in univariate analysis. In the multivariate model analysis, only the American Society of Anesthesiology (ASA) score (OR 5.815 [2.9-11.67], P<0.0001), emergency surgery (OR 5.066 [2.24-11.48], P<0.0001), and need for surgical reintervention (OR 5.195 [1.78-15.16], P=0.003) were associated with hospital mortality. CONCLUSIONS Despite considerable challenges, in this large retrospective cohort, perioperative mortality was similar to that of pre-pandemic practice. Efforts should be made to optimize personnel issues, while maintaining COVID-19-free surgical pathways, to adequately address patients' surgical needs during the following waves of the pandemic.

Isolated liver trauma: A clinical perspective in a non-emergency center for liver surgery.

The management of liver trauma is, currently, still heterogeneous ranging from conservative to major invasive liver resections. When appropriate, these cases should be referred to a regional care center. The objective of this study was to analyze the expertise of a non-emergency center for liver surgery from Romania after initial stabilization in county hospitals. This study is a monocentric, retrospective, observational study, including 12 patients with hepatic trauma after a car accident, admitted between 2015 and 2019. We analyzed various clinical and biochemical data as independent variables, and the main outcome was considered the intensive care unit (ICU) length of stay. Our results revealed that intubation status at admission, norepinephrine infusion during surgery, hyperfibrinogenemia and duration of mechanical ventilation in patients with isolated liver trauma were correlated with prolonged ICU length of stay. Further prospective, more comprehensive studies are needed in order to evaluate the exact prognostic factors in terms of short- and long-term mortality.

Dynamics of serum α-fetoprotein in viral hepatitis C without hepatocellular carcinoma.

Viral hepatitis C represents a significant liver pathology worldwide, with a detrimental impact on national health systems. The present study aimed to correlate the levels of serum α-fetoprotein (AFP) with prognostic tools such as Fibroscan®, the presence of mixed cryoglobulinemia, and various demographic and standard biochemical markers, in patients with chronic hepatitis C, unrelated to hepatocellular carcinoma (HCC). A clinical study was designed considering three study groups: Hepatitis C virus (HCV) group including 35 patients with chronic hepatitis C and detectible viral load; sustained viral response (SVR) group including 20 HCV patients without detectable virus load 12 weeks after therapy cessation; a control group represented by 37 healthy volunteers. It was observed that serum AFP was moderately increased in the HCV and SVR groups and was positively correlated with aspartate transaminase (AST), alkaline phosphatase (AP), and γ-glutamyl transferase (GGT). The incidence of mixed cryoglobulinemia was increased in the HCV group, and the degree of fibrosis assessed by Fibroscan® was increased in both the HCV and SVR groups. In conclusion, the data revealed that a moderate increase in AFP levels could be present in patients with HCV even in the absence of HCC, unrelated to viral load or therapy response and that there was a linear positive correlation between serum levels of AFP and the degree of hepatic cytolysis and cholestasis. Additionally, mixed cryoglobulinemia was present in HCV patients with patent viral load, decreasing in those with SVR after therapy cessation unrelated to any renal impairment, while the degree of fibrosis was increased in HCV-infected patients, with no reversibility 12 weeks after successful therapy.

Maternal Citicoline-Supplemented Diet Improves the Response of the Immature Hippocampus to Perinatal Asphyxia in Rats.

BACKGROUND: Citicoline represents a dietary source of choline, an essential nutrient, and precursor of cell membrane components, highly required during development and post-injury recovery. OBJECTIVES: We previously showed that perinatal asphyxia (PA) induces hippocampal neuroinflammation and injury that are subject to epigenetic change by maternal diet. The present study investigates maternal citicoline-supplemented diet (CSD) impact on offspring hippocampal response to PA. METHODS: Six-day-old Wistar rats from mothers with standard-diet or CSD were exposed to PA. The hippocampal inflammation and injury were assessed by interleukin-1 beta (IL-1b), tumor necrosis factor-alpha (TNFα), and S-100B protein (S-100B), 24-48 h post-asphyxia. The microRNAs species miR124, miR132, miR134, miR146, and miR15a were measured from the hippocampus 24 h post-asphyxia, to investigate its epigenetic response to PA and maternal diet. At maturity, the offspring's behavior was analyzed using open field (OFT), T-maze (TMT), and forced swimming (FST) tests. RESULTS: Our data show that the maternal CSD decreased IL-1b (p = 0.02), TNFα (p = 0.007), and S100B (p = 0.01) at 24 h postexposure, upregulated miR124 (p = 0.03), downregulated miR132 (p = 0.002) and miR134 (p = 0.001), shortened the immobility period in FST (p = 0.01), and increased the percentage of passed trials in TMT (p = 0.01) compared to standard-diet. CONCLUSIONS: Maternal CSD reduces hippocampal inflammation and S100B level, triggers epigenetic changes related to homeostatic synaptic plasticity, memory formation, and neuronal tolerance to asphyxia, decreases the depressive-like behavior, and improves the lucrative memory in offspring subjected to PA. Thus, citicoline could be valuable as a maternal dietary strategy in improving the brain response to PA.

Maternal High-Fat Diet Modifies the Immature Hippocampus Vulnerability to Perinatal Asphyxia in Rats.

BACKGROUND: High-fat diet (HFD) is a detrimental habit with harmful systemic consequences, including low-grade, long-lasting inflammation. During pregnancy, HFD can induce developmental changes. Moreover, HFD-related maternal obesity might enhance the risk of peripartum complications including hypoxic-ischemic encephalopathy secondary to perinatal asphyxia (PA). OBJECTIVES: Following our previous results showing that PA increases neuroinflammation and neuronal injury in the immature hippocampus and modifies hippocampal epigenetic programming, we further aimed to establish the impact of maternal HFD on offspring hippocampus response to PA. METHODS: We assessed hippocampal tumor necrosis factor alpha (TNFα), interleukin 1 beta -(IL-1b) and S-100B protein (S-100B), 24-48 h after PA exposure in postnatal day 6 Wistar rats, whose mothers received either the standard diet or HFD. The expression of small non-coding microRNA species miR124, miR132, miR134, miR146, and miR15a, as epigenetic markers for the maternal dietary influence on immature hippocampus response after PA, was determined 24 h after asphyxia exposure. Metabolic activity was measured using resazurin test in hippocampal cell suspension obtained 24 h after PA. RESULTS: Our results indicate that maternal HFD additionally increases hippocampal TNFα, IL-1b, and S-100B after PA. Also, PA associated with maternal HFD induces miR124 upregulation and miR132 downregulation relative to PA only. Metabolic activity was increased in hippocampal cells from pups whose mothers received HFD. CONCLUSION: HFD increases the PA-induced neuroinflammation and neuronal injury, and epigenetically influences homeostatic synaptic plasticity and neuronal tolerance to asphyxia, processes associated with a higher hippocampal cellular metabolism.

Trans-resveratrol enriched maternal diet protects the immature hippocampus from perinatal asphyxia in rats.

Trans-resveratrol (tRESV), a polyphenol with antioxidant properties, is common in many food sources, hence easily accessible for study as a maternal dietary supplement in perinatal asphyxia (PA). Hypoxic-ischemic encephalopathy secondary to PA affects especially vulnerable brain areas such as hippocampus and is a leading cause of neonatal morbidity. The purpose of this study is to identify new epigenetic mechanisms of brain inflammation and injury related to PA and to explore the benefit of tRESV enriched maternal diet. The hippocampal interleukin 1 beta (IL-1b), tumour necrosis factor alpha (TNFα) and S-100B protein, at 24-48h after 90min of asphyxia were assessed in postnatal day 6 rats whose mothers received either standard or tRESV enriched diet. The expression of non-coding microRNAs miR124, miR132, miR134, miR146 and miR15a as epigenetic markers of hippocampus response to PA was determined 24h post-asphyxia. Our results indicate that neural response to PA could be epigenetically controlled and that tRESV reduces asphyxia-related neuroinflammation and neural injury. Moreover, tRESV could increase, through epigenetic mechanisms, the tolerance to asphyxia, with possible impact on the neuronal maturation. Our data support the neuroprotective quality of tRESV when used as a supplement in the maternal diet on the offspring's outcome in PA.