Long-term impact of congenital Zika virus infection on the rat hippocampus: Neuroinflammatory, glial alterations and sex-specific effects.

Congenital Zika Syndrome (CZS) is a condition that arises when a neonate presents with abnormalities resulting from Zika virus infection during gestation. While microcephaly is a prominent feature of the syndrome, other forms of brain damage are also observed, often accompanied by significant neurological complications. It is therefore essential to investigate the long-term effects of CZS, with special attention to sex differences, particularly concerning hippocampal function, given its vulnerability to viral infections.

Protective effects of the PPAR agonist bezafibrate against disruption of redox and energy homeostasis, neuronal death, astroglial reactivity, and neuroinflammation induced in vivo by D-2-hydroxyglutaric acid in rat brain.

The biochemical hallmark of D-2-hydroxyglutaric aciduria is brain accumulation of D-2-hydroxyglutaric acid (D2HG). Patients present predominantly neurological manifestations, whose pathogenesis is still unknown. Thus, we examined the impact of elevated brain levels of D2HG, induced by intracerebral injection of this metabolite in juvenile rats, on redox and mitochondrial homeostasis and histochemical landmarks in the cerebral cortex.

Impact of peripheral immune cells in experimental neonatal hypoxia-ischemia: A systematic review and meta-analysis.

Infiltration of peripheral immune cells into the brain following neonatal hypoxia-ischemia (HI) contributes to increased neuroinflammation and brain injury. However, the specific roles of different immune cell types in neonatal brain injury remain poorly understood. Although existing evidence suggests a potential role for sexual dimorphism in HI outcomes, this aspect has been insufficiently investigated.

Impairment of neuromotor development and cognition associated with histopathological and neurochemical abnormalities in the cerebral cortex and striatum of glutaryl-CoA dehydrogenase deficient mice.

Patients with glutaric acidemia type I (GA I) manifest motor and intellectual disabilities whose pathogenesis has been so far poorly explored. Therefore, we evaluated neuromotor and cognitive abilities, as well as histopathological and immunohistochemical features in the cerebral cortex and striatum of glutaryl-CoA dehydrogenase (GCDH) deficient knockout mice (Gcdh), a well-recognized model of GA I. The effects of a single intracerebroventricular glutaric acid (GA) injection in one-day-old pups on the same neurobehavioral and histopathological/immunohistochemical endpoints were also investigated.

Methylphenidate Exposing During Neurodevelopment Alters Amino Acid Profile, Astrocyte Marker and Glutamatergic Excitotoxicity in the Rat Striatum.

There is a public health concern about the use of methylphenidate (MPH) since the higher prescription for young individuals and non-clinical purposes is addressed to the limited understanding of its neurochemical and psychiatric consequences. This study aimed to evaluate the impact of early and chronic MPH treatment on the striatum focusing on amino acid profile, glutamatergic excitotoxicity, redox status, neuroinflammation and glial cell responses. Male Wistar rats were treated with MPH (2.

Lactate administration causes long-term neuroprotective effects following neonatal hypoxia-ischemia.

Neonatal hypoxia-ischemia (HI) is one of the main causes of mortality and long-term disabilities in newborns, and the only clinical approach to treat this condition is therapeutic hypothermia, which shows some limitations. Thus, putative neuroprotective agents have been tested in animal models of HI. Lactate is a preferential metabolic substrate of the neonatal brain and has already been shown to produce beneficial neuroprotective outcomes in neonatal animals exposed to HI.

3-Hydroxy-3-Methylglutaric Acid Disrupts Brain Bioenergetics, Redox Homeostasis, and Mitochondrial Dynamics and Affects Neurodevelopment in Neonatal Wistar Rats.

3-Hydroxy-3-methylglutaric acidemia (HMGA) is a neurometabolic inherited disorder characterized by the predominant accumulation of 3-hydroxy-3-methylglutaric acid (HMG) in the brain and biological fluids of patients. Symptoms often appear in the first year of life and include mainly neurological manifestations. The neuropathophysiology is not fully elucidated, so we investigated the effects of intracerebroventricular administration of HMG on redox and bioenergetic homeostasis in the cerebral cortex and striatum of neonatal rats.

Acrobatic training prevents learning impairments and astrocyte remodeling in the hippocampus of rats undergoing chronic cerebral hypoperfusion: sex-specific benefits.

Background: Chronic cerebral hypoperfusion (CCH) leads to memory and learning impairments associated with degeneration and gliosis in the hippocampus. Treatment with physical exercise carries different therapeutic benefits for each sex. We investigated the effects of acrobatic training on astrocyte remodeling in the CA1 and CA3 subfields of the hippocampus and spatial memory impairment in male and female rats at different stages of the two-vessel occlusion (2VO) model.

Neutrophil-Lymphocyte Ratio as a Predictor of the Risk of Death in Severe Cases of COVID-19.

Background: Identifying clinical characteristics and risk factors, comorbid conditions, and complications arising from SARS-CoV-2 infection is important to predict the progression to more severe forms of the disease among hospitalized individuals to enable timely intervention and to prevent fatal outcomes. The aim of the study is to assess the possible role of the neutrophil/lymphocyte ratio (NLR) as a biomarker of the risk of death in patients with comorbidities hospitalized with COVID-19 in a tertiary hospital in southern Brazil.

Methods: This is a prospective cohort study on patients with SARS-CoV-2 infection admitted to a hospital in the metropolitan region of Porto Alegre from September 2020 to March 2022.

Acrobatic training prevents motor deficits and neuronal loss in male and female rats following chronic cerebral hypoperfusion.

Background: Chronic cerebral hypoperfusion in vascular dementia leads to memory and motor deficits; Physical exercise improves these aspects and promotes neuroprotection. Sexual dimorphism may significantly influence both ischemic and exercise outcomes.

Aims: The aim of this study was to investigate the effects of 2VO (Two-Vessel occlusion) and the acrobatic training on motor function, functional performance, and tissue loss in male and female rats.

Simvastatin Differentially Modulates Glial Functions in Cultured Cortical and Hypothalamic Astrocytes Derived from Interferon α/β Receptor Knockout mice.

Astrocytes have key regulatory roles in central nervous system (CNS), integrating metabolic, inflammatory and synaptic responses. In this regard, type I interferon (IFN) receptor signaling in astrocytes can regulate synaptic plasticity. Simvastatin is a cholesterol-lowering drug that has shown anti-inflammatory properties, but its effects on astrocytes, a main source of cholesterol for neurons, remain to be elucidated.

Serum of COVID-19 patients changes neuroinflammation and mitochondrial homeostasis markers in hippocampus of aged rats.

Patients affected by COVID-19 present mostly with respiratory symptoms but acute neurological symptoms are also commonly observed. Furthermore, a considerable number of individuals develop persistent and often remitting symptoms months after infection, characterizing the condition called long-COVID. Since the pathophysiology of acute and persistent neurological manifestations is not fully established, we evaluated the expression of different genes in hippocampal slices of aged rats exposed to the serum of a post-COVID (sPC) individual and to the serum of patients infected by SARS-CoV-2 [Zeta (sZeta) and Gamma (sGamma) variants].

Bumetanide Attenuates Cognitive Deficits and Brain Damage in Rats Subjected to Hypoxia-Ischemia at Two Time Points of the Early Postnatal Period.

Neonatal hypoxia-ischemia (HI) is one of the main causes of tissue damage, cell death, and imbalance between neuronal excitation and inhibition and synaptic loss in newborns. GABA, the major inhibitory neurotransmitter of the central nervous system (CNS) in adults, is excitatory at the onset of neurodevelopment and its action depends on the chloride (Cl) cotransporters NKCC1 (imports Cl) and KCC2 (exports Cl) expression. Under basal conditions, the NKCC1/KCC2 ratio decreases over neurodevelopment.

Glioprotective effects of resveratrol in hypothalamic astrocyte cultures obtained from interferon receptor knockout (IFNα/βR) mice.

Astrocytes play essential roles in the central nervous system (CNS), such as the regulation of glutamate metabolism, antioxidant defenses, and inflammatory/immune responses. Moreover, hypothalamic astrocytes seem to be crucial in the modulation of inflammatory processes, including those related to type I interferon signaling. In this regard, the polyphenol resveratrol has emerged as an important glioprotective molecule to regulate astrocyte functions.

Consequences of oxygen deprivation on myelination and sex-dependent alterations.

Oxygen deprivation is one of the main causes of morbidity and mortality in newborns, occurring with a higher prevalence in preterm infants, reaching 20 % to 50 % mortality in newborns in the perinatal period. When they survive, 25 % exhibit neuropsychological pathologies, such as learning difficulties, epilepsy, and cerebral palsy. White matter injury is one of the main features found in oxygen deprivation injury, which can lead to long-term functional impairments, including cognitive delay and motor deficits.

L-2-Hydroxyglutaric Acid Administration to Neonatal Rats Elicits Marked Neurochemical Alterations and Long-Term Neurobehavioral Disabilities Mediated by Oxidative Stress.

L-2-Hydroxyglutaric aciduria (L-2-HGA) is an inherited neurometabolic disorder caused by deficient activity of L-2-hydroxyglutarate dehydrogenase. L-2-Hydroxyglutaric acid (L-2-HG) accumulation in the brain and biological fluids is the biochemical hallmark of this disease. Patients present exclusively neurological symptoms and brain abnormalities, particularly in the cerebral cortex, basal ganglia, and cerebellum.

Short-term effects of therapeutic hypothermia following hypoxia-ischemia in neonatal male and female rats.

Nowadays, the only treatment for human babies suffering from hypoxia-ischemia (HI) is therapeutic hypothermia (TH). However, a better understanding of the specific effects of TH in males and females is important to improve its clinical application. The present study evaluated the short-term effects of TH on the brain injury and behavioral outcomes in male and female neonatal rats submitted to neonatal HI.

SARS-CoV-2-Induced Amyloidgenesis: Not One, but Three Hypotheses for Cerebral COVID-19 Outcomes.

The main neuropathological feature of Alzheimer's disease (AD) is extracellular amyloid deposition in senile plaques, resulting from an imbalance between the production and clearance of amyloid beta peptides. Amyloid deposition is also found around cerebral blood vessels, termed cerebral amyloid angiopathy (CAA), in 90% of AD cases. Although the relationship between these two amyloid disorders is obvious, this does not make CAA a characteristic of AD, as 40% of the non-demented population presents this derangement.

A Review of In Silico Research, SARS-CoV-2, and Neurodegeneration: Focus on Papain-Like Protease.

Since the appearance of SARS-CoV-2 and the COVID-19 pandemic, the search for new approaches to treat this disease took place in the scientific community. The in silico approach has gained importance at this moment, once the methodologies used in this kind of study allow for the identification of specific protein-ligand interactions, which may serve as a filter step for molecules that can act as specific inhibitors. In addition, it is a low-cost and high-speed technology.

Therapeutic hypothermia for the treatment of neonatal hypoxia-ischemia: sex-dependent modulation of reactive astrogliosis.

Therapeutic hypothermia (TH) is the standard treatment for neonatal hypoxia-ischemia (HI) with a time window limited up to 6 h post injury. However, influence of sexual dimorphism in the therapeutic window for TH has not yet been elucidated in animal models of HI. Therefore, the aim of this study was to investigate the most effective time window to start TH in male and female rats submitted to neonatal HI.

Effects of acrobatic training on spatial memory and astrocytic scar in CA1 subfield of hippocampus after chronic cerebral hypoperfusion in male and female rats.

Chronic cerebral hypoperfusion leads to neuronal loss in the hippocampus and spatial memory impairments. Physical exercise is known to prevent cognitive deficits in animal models; and there is evidence of sex differences in behavioral neuroprotective approaches. The aim of present study was to investigate the effects of acrobatic training in male and female rats submitted to chronic cerebral hypoperfusion.

Coumestrol pre-treatment improves spatial learning and memory deficits following transient cerebral ischemia recruiting hippocampal GluR2 AMPA receptors.

Transient global ischemia is a leading cause of learning and memory dysfunction and induces a pattern of delayed neuronal death in the CA1 subfield of the hippocampus by down-regulating GluR2 mRNA AMPA receptors in this cerebral area. This study sought to investigate the neuroprotective effect of coumestrol against spatial memory impairment induced by global ischemia that leads to neural death by reducing the GluR2 receptors content in the hippocampal CA1 area. Our studies demonstrated that coumestrol administration prevented spatial memory deficits in mice.

Role of Brain Β-endorphin in Memory Modulation Revisited.

A possible role for the brain β-endorphin system in memory modulation was proposed by Ivan Izquierdo more than 30 years ago. Along with pharmacologic evidence of the effects of morphine and naloxone administered immediately after training in avoidance tasks and with the demonstration of medial-basal hypothalamus β-endorphin release after novelty detection, it was hypothesized that an endogenous opioid state present in the labile period of consolidation will be part of the memory of the newly acquired information. The fact that pre-test novelty exposure, through release of β-endorphin, or the injection of opioids facilitate retrieval supports that.

Extract Administration Prevents HI-Induced Oxidative Stress, Inflammatory Response, Behavioral Impairments, and Tissue Damage in Rats.

The disruption of redox homeostasis and neuroinflammation are key mechanisms in the pathogenesis of brain hypoxia-ischemia (HI); medicinal plants have been studied as a therapeutic strategy, generally associated with the prevention of oxidative stress and inflammatory response. This study evaluates the neuroprotective role of the fruit extract (PTE) in neonatal rats submitted to experimental HI. The HI insult provoked a marked increase in the lipoperoxidation levels and glutathione peroxidase (GPx) activity, accompanied by a decrease in the brain concentration of glutathione (GSH).