Effects of riboflavin in the treatment of brain damage caused by oxygen deprivation: an integrative systematic review.

Brain oxygen deprivation causes morphological damage involved in the formation of serious pathological conditions such as stroke and cerebral palsy. Therapeutic methods for post-hypoxia/anoxia injuries are limited and still have deficiencies in terms of safety and efficacy. Recently, clinical studies of stroke have reported the use of drugs containing riboflavin for post-injury clinical rehabilitation, however, the effects of vitamin B2 on exposure to cerebral oxygen deprivation are not completely elucidated. This review aimed to investigate the potential antioxidant, anti-inflammatory and neuroprotective effects of riboflavin in cerebral hypoxia/anoxia. After a systematic search, 21 articles were selected, 8 preclinical and 12 clinical studies, and 1 translational study. Most preclinical studies used B2 alone in models of hypoxia in rodents, with doses of 1-20 mg/kg (in vivo) and 0.5-5 µM (in vitro). Together, these works suggested greater regulation of lipid peroxidation and apoptosis and an increase in neurotrophins, locomotion, and cognition after treatment. In contrast, several human studies have administered riboflavin (5 mg) in combination with other Krebs cycle metabolites, except one study, which used only B2 (20 mg). A reduction in lactic acidosis and recovery of sensorimotor functions was observed in children after treatment with B2, while adults and the elderly showed a reduction in infarct volume and cognitive rehabilitation. Based on findings from preclinical and clinical studies, we conclude that the use of riboflavin alone or in combination acts beneficially in correcting the underlying brain damage caused by hypoxia/anoxia and its inflammatory, oxidative, and behavioral impairments.

Effectiveness of Polyphenols on Perinatal Brain Damage: A Systematic Review of Preclinical Studies.

Polyphenol supplementation during early life has been associated with a reduction of oxidative stress and neuroinflammation in diseases caused by oxygen deprivation, including cerebral palsy, hydrocephaly, blindness, and deafness. Evidence has shown that perinatal polyphenols supplementation may alleviate brain injury in embryonic, fetal, neonatal, and offspring subjects, highlighting its role in modulating adaptative responses involving phenotypical plasticity. Therefore, it is reasonable to infer that the administration of polyphenols during the early life period may be considered a potential intervention to modulate the inflammatory and oxidative stress that cause impairments in locomotion, cognitive, and behavioral functions throughout life. The beneficial effects of polyphenols are linked with several mechanisms, including epigenetic alterations, involving the AMP-activated protein kinase (AMPK), nuclear factor kappa B (NF-κB), and phosphoinositide 3-kinase (PI3K) pathways. To highlight these new perspectives, the objective of this systematic review was to summarize the understanding emerging from preclinical studies about polyphenol supplementation, its capacity to minimize brain injury caused by hypoxia-ischemia in terms of morphological, inflammatory, and oxidative parameters and its repercussions for motor and behavioral functions.

Potential role of Limosilactobacillus fermentum as a probiotic with anti-diabetic properties: A review.

Oxidative stress, inflammation, and gut microbiota impairments have been implicated in the development and maintenance of diabetes mellitus. Strategies capable of recovering the community of commensal gut microbiota and controlling diabetes mellitus have increased in recent years. Some lactobacilli strains have an antioxidant and anti-inflammatory system capable of protecting against oxidative stress, inflammation, and diabetes mellitus. Experimental studies and some clinical trials have demonstrated that Limosilactobacillus fermentum strains can beneficially modulate the host antioxidant and anti-inflammatory system, resulting in the amelioration of glucose homeostasis in diabetic conditions. This review presents and discusses the currently available studies on the identification of Limosilactobacillus fermentum strains with anti-diabetic properties, their sources, range of dosage, and the intervention time in experiments with animals and clinical trials. This review strives to serve as a relevant and well-cataloged reference of Limosilactobacillus fermentum strains capable of inducing anti-diabetic effects and promoting health benefits.

Evidence for Quercetin as a Dietary Supplement for the Treatment of Cardio-Metabolic Diseases in Pregnancy: A Review in Rodent Models.

Quercetin supplementation during pregnancy and lactation has been linked to a lower risk of maternal cardio-metabolic disorders such as gestational diabetes mellitus (GDM), dyslipidemia, preeclampsia, attenuation of malnutrition-related conditions, and gestational obesity in animal studies. Pre-clinical studies have shown that maternal supplementation with quercetin reduces cardio-metabolic diseases in dams and rodents' offspring, emphasizing its role in modifying phenotypic plasticity. In this sense, it could be inferred that quercetin administration during pregnancy and lactation is a viable strategy for changing cardio-metabolic parameters throughout life. Epigenetic mechanisms affecting the AMP-activated protein kinase (AMPK), nuclear factor-kappa B (NF-κB), and phosphoinositide 3-kinase (PI3 K) pathways could be associated with these changes. To highlight these discoveries, this review outlines the understanding from animal studies investigations about quercetin supplementation and its capacity to prevent or decrease maternal and offspring cardio-metabolic illnesses and associated comorbidities.

Serotonergic mechanisms associated with experimental models of hypoxia: A systematic review.

PURPOSE: The aim of this systematic review was to explore and discuss the literature concerning the effects of hypoxia or anoxia during the perinatal period on the serotoninergic network in rodents, through mechanisms that lead to changes in serotonergic neurons, levels, segments of central nervous system affected, 5-HT transporter, and 5-HT receptor. METHODS: Literature searches were performed in Embase, Medline (PubMed), Web of Science, and SCOPUS, from April to July 2021, with a total of 1045 published studies found. Using a predefined protocol, as registered on the CAMARADES website, 10 articles were included in this review. The PRISMA statement was used for reporting this systematic review. The internal validity was assessed using the SYRCLE's risk of bias tool. RESULTS: Our main findings show that hypoxia in the first days of postnatal life led to a disturbance in the serotonergic system with reduced in 5-HT fibers, reduced brain levels of 5-HT and 5-HIAA, reduced SERT protein expression, and reduced receptor 5-HT7 . Putative mechanisms involving damage in the serotoninergic system include retrograde cell death resulting from primary damage mainly in forebrain areas, which impairs remote areas including serotonergic raphe nuclei. Other probable mechanisms associated with the serotoninergic network damage may be triggered by excitotoxic lesion and neuroinflammation. CONCLUSION: Hypoxia at the beginning of an animal's life leads to modification of the serotonergic components associated with putative mechanisms that include cell damage and neuroinflammation.

Perinatal undernutrition associated to experimental model of cerebral palsy increases adverse effects on chewing in young rats.

The aim of the present study was to investigate the effect of perinatal undernutrition on the sensorimotor pattern of chewing in rats submitted to cerebral palsy experimental model. A total of 60 male Wistar rats were randomly distributed into four groups: Nourished/Control (NC, n=15), Nourished/Cerebral Palsy (NCP, n=15); Undernourished/Control (UC, n=15) and Undernourished/Cerebral Palsy (UCP, n=15). Animals of cerebral palsy (CP) group were subjected to an experimental model based on the combination of perinatal anoxia associated with sensorimotor restriction of the hindlimb. In the rats were evaluated body weight gain, intake of breast milk, feed post-weaning consumption, parameters of the chewing, intra-oral sensitivity and muscle properties (muscle weight and distribution of types of fibers) of the masseter and digastric. Animals from undernourished CP group showed greater reduction in most data evaluated including body weight (P<0.05), food intake post-weaning (P<0.05), frequency of chewing cycles (P<0.05), duration of the reactions of "taste" (P<0.05), muscle weight and decrease of the proportion of type IIB fibers in the masseter muscle (P<0.05). These results demonstrated in rats submitted a cerebral palsy that perinatal undernutrition intensifies the damage in morphological and functional parameters of chewing.