There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.

Neuronal ischemia results in chloride gradient alterations which impact the excitatory–inhibitory balance, volume regulation, and neuronal survival. Thus, the Na⁺/K⁺/Cl⁻ co-transporter (NKCC1), the K⁺/ Cl⁻ co-transporter (KCC2), and the gamma-aminobutyric acid A (GABA_A) receptor may represent therapeutic targets in stroke, but a time-dependent effect on neuronal viability could influence the outcome. We, therefore, successively blocked NKCC1, KCC2, and GABA_A (with bumetanide, DIOA, and gabazine, respectively) or activated GABA_A (with isoguvacine) either during or after oxygen-glucose deprivation (OGD). Primary hippocampal cultures were exposed to a 2-h OGD or sham normoxia treatment, and viability was determined using the resazurin assay. Neuronal viability was significantly reduced after OGD, and was further decreased by DIOA treatment applied during OGD (p < 0.01) and by gabazine applied after OGD (p < 0.05). Bumetanide treatment during OGD increased viability (p < 0.05), while isoguvacine applied either during or after OGD did not influence viability. Our data suggests that NKCC1 and KCC2 function has an important impact on neuronal viability during the acute ischemic episode, while the GABA_A receptor plays a role during the subsequent recovery period. These findings suggest that pharmacological modulation of transmembrane chloride transport could be a promising approach during stroke and highlight the importance of the timing of treatment application in relation to ischemia-reoxygenation.

Background: Secondary thrombotic thrombocytopenic purpura (TTP) due to interferon beta-1a intramuscular (im) treatment is an uncommon adverse effect with only a few cases in multiple sclerosis patients reported worldwide. TTP together with haemolytic uremic syndrome (HUS) are classic forms of thrombotic microangiopathy, characterized by small-vessel platelet micro-thrombi that manifest clinically in a similar manner. Most common signs and symptoms include bruises and ecchymosis, neurologic symptoms and renal impairment. Interferon beta-1a represents one of the first-line therapies for relapsing-remitting multiple sclerosis due to its accessibility and efficacy. Case presentation: A 36-year-old woman who was previously diagnosed with relapsing-remitting multiple sclerosis had received weekly intramuscular injections with beta-interferon-1a (Avonex 30 mcg). After 9 months of treatment, she presented bruises and ecchymosis on her limbs and torso, epistaxis, gingival bleeding aggravated within 48 h and a persistent headache that was non-responsive to common analgesics. Haematology tests revealed typical results for thrombotic microangiopathy, including severe thrombocytopenia (4000/mm³) and microangiopathic haemolytic anaemia with frequent schistocytes on the peripheral blood smear. Once the beta-interferon administration was ceased and upon the initiation of methylprednisolone, the symptoms remitted. Conclusions: In this case study, we portrayed the particular association between the remission phase of multiple sclerosis and the violent onset of interferon-induced thrombotic thrombocytopenic purpura.

Perinatal asphyxia (PA) and hypoxic-ischemic encephalopathy can result in severe, long-lasting neurological deficits. In vitro models, such as oxygen–glucose deprivation (OGD), are used experimentally to investigate neuronal response to metabolic stress. However, multiple variables can affect the severity level of OGD/PA and may confound any measured treatment effect. Oxytocin (OXT) has emerged as a potential neuroprotective agent against the deleterious effects of PA. Previous studies have demonstrated OXT’s potential to enhance neuronal survival in immature hippocampal cultures exposed to OGD, possibly by modulating gamma-aminobutyric acid-A receptor activity. Moreover, OXT’s precise impact on developing hippocampal neurons under different severities of OGD/PA remains uncertain. In this study, we investigated the effects of OXT (0.1 µM and 1 µM) on 7-day-old primary rat hippocampal cultures subjected to 2 h OGD/sham normoxic conditions. Cell culture viability was determined using the resazurin assay. Our results indicate that the efficacy of 1 µM OXT treatment varied according to the severity of the OGD-induced lesion, exhibiting a protective effect (p = 0.022) only when cellular viability dropped below 49.41% in non-treated OGD cultures compared to normoxic ones. Furthermore, administration of 0.1 µM OXT did not yield significant effects, irrespective of lesion severity (p > 0.05). These findings suggest that 1 µM OXT treatment during OGD confers neuroprotection exclusively in severe lesions in hippocampal neurons after 7 days in vitro. Further research is warranted to elucidate the mechanisms involved in OXT-mediated neuroprotection.

Background and Objectives: Mortality in Late‐Onset Pompe Disease (LOPD) has been associated with the rapid progression of respiratory and motor impairment. However, an in‐depth approach to the exact causes of death in these patients is still lacking. Methods: In this retrospective cohort study, we analyzed the cause of death and the comorbidities of all deceased patients from the French Late‐Onset Pompe Disease registry. Results: By the time of the last extraction, 60 patients diagnosed with LOPD and monitored were registered as deceased in the French national registry, out of a total of 260 patients included. The median age of death was 70.5 years, while the median age of diagnosis was 58 years. The causes of death were divided into disease‐related, accounting for 46.6% of deaths, and non‐disease‐related, comprising 28.3% of total deaths. Fifteen patients (25%) died of an unknown cause. The most frequent etiology of disease‐related death was respiratory failure ( n = 14), while for the non‐disease‐related group, malignant neoplasm was the most common ( n = 8). Patients in the non‐disease‐related death group had significantly higher forced vital capacity (FVC) values compared to those in the disease‐related death group (54.7% vs. 38%). Treatment‐wise, the median period elapsed from diagnosis to ERT introduction was higher in the disease‐related group. Discussion: This is the first study to focus on the specific causes of death of LOPD patients. The majority of the LOPD deaths in the French registry were attributed to respiratory failure and malignant neoplasms.