Central Nervous System Research Articles

Severe Hyperandrogenism in 46,XX Congenital Adrenal Hyperplasia: Molecular Physiopathology, Late Diagnoses, and Personalized Management

Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive endocrine disorders characterized by alteration in adrenal hormonal secretions. The most common form is caused by CYP21A2 mutations that result in 21-hydroxylase deficiency. Clinical features can vary, from salt-wasting forms, characterized by a lack of mineralocorticoid activity with a risk of perinatal-onset adrenal crises, to “simple-virilizing” forms with sufficient aldosterone secretion, up to milder “non-classical” forms, with a variable grade of hyperandrogenism but no severe hormonal deficiencies. During pregnancy, CAH 46,XX fetuses are exposed to elevated androgen levels, leading to a variable grade of virilization and potential central nervous system effects if untreated. These patients are usually (but not always) assigned female at birth, but some cases may be misdiagnosed and assigned male, potentially inducing fertility, gender identity, and sexual behavior issues in adulthood. In these patients, the benefits and risks of a late gender transition should be carefully evaluated. In this paper, we reviewed the literature concerning the most interesting peculiarities of these conditions.

Impact of Serum Folate and Vitamin B12 on Mental Health in Patient Admitted at Razi Psychiatric Hospital

Vitamin B12 (cobalamin) is one of the essential vitamins that affect various systems in the body, including the central nervous system and plays an important role in the metabolism of the nervous system, although its exact role under pathological conditions is not fully understood. The present study aimed to assessing vitamin B12 & serum folate in patient admitted at Razi psychiatric hospital. A cross section study subjects were inpatients with psychiatric disorder, patients from 21 to 60 years old. In this group of 40 psychiatric patients, there is no evidence of clinically relevant changes in serum vitamin B12 and folate level. Vitamin B12 deficiency can occur despite “normal” serum cobalamin levels; therefore, measuring homocysteine and methyl malonic acid can decrease false-negative findings.

Efficacy and safety of first-line high-dose cytarabine in patients with primary CNS lymphoma ineligible for high-dose methotrexate: a case series

Abstract Introduction Despite recent significant advances, the treatment of elderly patients with primary central nervous system lymphoma (PCNSL) is still challenging due to comorbidities, poor baseline performance status (PS), and drug toxicities. There are proposals to use high-dose cytarabine (HD-araC) in these patients. Results Our retrospective study aimed to assess the efficacy and toxicity of HD-araC as an upfront treatment for patients with PCNSL who are ineligible for high-dose methotrexate (HD-MTX). Methods We identified 12 consecutive patients with newly diagnosed PCNSL (out of a total of 68) who received first-line treatment with HD-araC, with or without rituximab (R). Most of them had poor PS and relevant comorbidities. Six patients received this treatment upfront, while the other six received it after discontinuing HD-MTX-(based) therapy. Treatment with HD-araC resulted in poor outcome, limited response, and severe hematological and infectious complications. Patients who had previously received at least one cycle of HD-MTX appeared to have slightly better outcomes, highlighting the importance of HD-MTX in the treatment of PCNSL. Conclusion Our case series showed limited efficacy and substantial toxicity of (R)-HD-araC in patients with PCNSL ineligible for HD-MTX. This treatment should be omitted in elderly/frail patients to avoid further compromising their quality of life.

CNS macrophage contributions to myelin health.

Myelin is the membrane surrounding neuronal axons in the central nervous system (CNS), produced by oligodendrocytes to provide insulation for electrical impulse conduction and trophic/metabolic support. CNS dysfunction occurs following poor development of myelin in infancy, myelin damage in neurological diseases, and impaired regeneration of myelin with disease progression in aging. The lack of approved therapies aimed at supporting myelin health highlights the critical need to identify the cellular and molecular influences on oligodendrocytes. CNS macrophages have been shown to influence the development, maintenance, damage and regeneration of myelin, revealing critical interactions with oligodendrocyte lineage cells. CNS macrophages are comprised of distinct populations, including CNS-resident microglia and cells associated with CNS border regions (the meninges, vasculature, and choroid plexus), in addition to macrophages derived from monocytes infiltrating from the blood. Importantly, the distinct contribution of these macrophage populations to oligodendrocyte lineage responses and myelin health are only just beginning to be uncovered, with the advent of new tools to specifically identify, track, and target macrophage subsets. Here, we summarize the current state of knowledge on the roles of CNS macrophages in myelin health, and recent developments in distinguishing the roles of macrophage populations in development, homeostasis, and disease.

Polymer nanotherapeutics: A promising approach toward microglial inhibition in neurodegenerative diseases.

Nanoparticles (NPs) that target multiple transport mechanisms facilitate targeted delivery of active therapeutic agents to the central nervous system (CNS) and improve therapeutic transport and efficacy across the blood-brain barrier (BBB). CNS nanotherapeutics mostly target neurons and endothelial cells, however, microglial immune cells are the first line of defense against neuronal damage and brain infections. Through triggering release of inflammatory cytokines, chemokines and proteases, microglia can however precipitate neurological damage-a significant factor in neurodegenerative diseases. Thus, microglial inhibitory agents are attracting much attention among those researching and developing novel treatments for neurodegenerative disorders. The most established inhibitors of microglia investigated to date are resveratrol, curcumin, quercetin, and minocycline. Thus, there is great interest in developing novel agents that can bypass or easily cross the BBB. One such approach is the use of modified-nanocarriers as, or for, delivery of, therapeutic agents to the brain and wider CNS. For microglial inhibition, polymeric NPs are the preferred vehicles for choice. Here, we summarize the immunologic and neuroinflammatory role of microglia, established microglia inhibitor agents, challenges of CNS drug delivery, and the nanotherapeutics explored for microglia inhibition to date. We also discuss applications of the currently considered "most useful" polymeric NPs for microglial-inhibitor drug delivery in CNS-related diseases.

Interplays Between Matrix Metalloproteinases and Neurotropic Viruses: An Overview.

Matrix metalloproteinases (MMPs) are a diverse group of proteases involved in various physiological and pathological processes through modulation of extracellular matrix (ECM) components, cytokines, and growth factors. In the central nervous system (CNS), MMPs play a major role in CNS development, plasticity, repair, and reorganisation contributing to learning, memory, and neuroimmune response to injury. MMPs are also linked to various neurological disorders such as Alzheimer's disease, Parkinson's disease, cerebral aneurysm, stroke, epilepsy, multiple sclerosis, and brain cancer suggesting these proteases as key regulatory factors in the nervous system. Moreover, MMPs have been involved in the pathogenesis of neurotropic viral infections via dysregulation of various cellular processes, which may highlight these factors as potential targets for the treatment and control of neurological complications associated with viral pathogens. This review provides an overview of the roles of MMPs in various physiological processes of the CNS and their interactions with neurotropic viral pathogens.

The Role of the Vagus Nerve in the Microbiome and Digestive System in Relation to Epilepsy.

The Enteric Nervous System (ENS) is described as a division of the Peripheral Nervous System (PNS), located within the gut wall and it is formed by two main plexuses: the myenteric plexus (Auerbach's) and the submucosal plexus (Meissner's). The contribution of the ENS to the pathophysiology of various neurological diseases such as Parkinson's or Alzheimer's disease has been described in the literature, while some other studies have found a connection between epilepsy and the gastrointestinal tract. The above could be explained by cholinergic neurons and neurotransmission systems in the myenteric and submucosal plexuses, regulating the vagal excitability effect. It is also understandable, as the discharges arising in the amygdala are transmitted to the intestine through projections the dorsal motor nucleus of the vagus, giving rise to efferent fibers that stimulate the gastrointestinal tract and consequently the symptoms at this level. Therefore, this review's main objective is to argue in favor of the existing relationship of the ENS with the Central Nervous System (CNS) as a facilitator of epileptogenic or ictogenic mechanisms. The gut microbiota also participates in this interaction; however, it depends on many individual factors of each human being. The link between the ENS and the CNS is a poorly studied epileptogenic site with a big impact on one of the most prevalent neurological conditions such as epilepsy.

Soft, precision engineered porous, hydrogel scaffolds mechanically tailored toward applications in the central nervous system

Diseases and traumatic injuries to the central nervous system (CNS) demand the development of new biomaterials to improve healing and treatment options. Matching material mechanical properties to specific tissues and optimizing material porous structures are central goals for improving biomaterials. However, biomaterials with both precision-controlled porous structures and brain-matched mechanical properties (low modulus) are still lacking. In this study, we developed soft hydrogel scaffolds with mechanical properties similar to that of CNS tissues, and a uniform 40 µm porous structure—40 µm pores have been shown to be optimal for healing in many tissues. The two characteristics were achieved by a new fabrication process combining phase separation and sphere templating. The resulting scaffolds are non-cytotoxic according to the ISO 10993-5 standard. In addition, the three-dimensional culture of microglial cells within the scaffolds demonstrates cell attachment and maintenance of a rounded, quiescent morphology, potentially due to spatial confinement. These results justify further in vivo studies and suggest broad potential in CNS applications, such as brain-computer interfaces, neural regeneration, and basic neurobiology. Subject classification codes: Neural Interfaces, soft hydrogel, synthetic biomaterials

Shh regulates M2 microglial polarization and fibrotic scar formation after ischemic stroke

BackgroundFibrotic scar formation is a critical pathological change impacting tissue reconstruction and functional recovery after ischemic stroke. The regulatory mechanisms behind fibrotic scarring in the central nervous system (CNS) remain largely unknown. While macrophages are known to play a role in fibrotic scar formation in peripheral tissues, the involvement of microglia, the resident immune cells of the CNS, in CNS fibrosis requires further exploration. The Sonic Hedgehog (Shh) signaling pathway, pivotal in embryonic development and tissue regeneration, is also crucial in modulating fibrosis in peripheral tissues. However, the impact and regulatory mechanisms of Shh on fibrotic scar formation post-ischemic stroke have not been thoroughly investigated. MethodsThis study explores whether Shh can regulate fibrotic scar formation post-ischemic stroke and its underlying mechanisms through in vivo and in vitro manipulation of Shh expression. ResultsOur results showed that Shh expression was upregulated in the serum of acute ischemic stroke patients, as well as in the serum, CSF, and ischemic regions of MCAO/R mice. Moreover, the upregulation of Shh expression was positively correlated with fibrotic scar formation and M2 microglial polarization. Shh knockdown inhibited fibrotic scar formation and M2 microglial polarization while aggravating neurological deficits in MCAO/R mice. In vitro, adenoviral knockdown or Smoothened Agonist (SAG) activation of Shh expression in BV2 cells following OGD/R regulated their polarization and influenced the expression of TGFβ1 and PDGFA, subsequently affecting fibroblast activation. ConclusionThese results suggest that Shh regulates M2 microglial polarization and fibrotic scar formation after cerebral ischemia.

Resting-state networks in chronic tinnitus: Increased connectivity between thalamus and visual areas

Tinnitus is thought to be associated with aberrant spontaneous activity in the central nervous system. Previous resting-state fMRI findings support this hypothesis and have shown a variety of alterations in neural activity in people with tinnitus compared to people without tinnitus. However, there is little replication of findings. Therefore, the current study aimed to extend on previous findings by investigating eight common resting-state networks (i.e. auditory, default mode, sensorimotor, visual, salience, dorsal attention, frontoparietal and language networks) using a a control group (n = 36) and a group of tinnitus patients (n = 46) matched for age, sex and years of education. Hearing profiles matched up to 2kHz and had a small but significant difference between groups in the high frequency range. Functional connectivity (FC) with dorsolateral prefrontal cortex (DLPFC) was also investigated separately for the first time, as this region is proposed to be core to tinnitus distress symptoms and most often used as a stimulation target in transcranial direct current stimulation (tDCS) research. The results showed that tinnitus patients had increased FC between bilateral thalamus and right visual association cortex compared to control participants. No differences were found with DLPFC, or with any of the resting-state networks (RSN), contrary to previous studies which have reported alterations in several RSNs.

Clinical characteristics of Behçet's disease in an Egyptian cohort

Background: Behçet's disease is a multi-systemic vasculitis characterized by recurring lesions in the skin mucosa and sight-threatening uveitis. The aim of the research: This research aimed to investigate the clinical features of Behçet's disease (BD) in individuals residing in Egypt. Patients and methods: 150 individuals with BD were recruited, examined, and put through a skin allergy test, musculoskeletal assessment, laboratory tests, and comprehensive medical history. The disease's activity was evaluated using the Behçet Disease Current Activity Form (BDCAF). Complete ophthalmological evaluation and imaging studies were performed according to the organ involved. Results: Cases were 116 men (77.3%) and 34 women (22.7%) (M: F 3.4:1). Their mean age was 34.05 ± 9.28 years, and the disease duration range was 1–20 years. Oral and genital aphthosis were reported in 86.7% and 82.0%, respectively. Eye affection was observed in 68.7%, mainly in anterior uveitis (35.3%). Vascular manifestations occurred in 58.7%, affecting primarily the venous side (31.3%) in the form of deep venous thrombosis (DVT). 32.7% had joint affection, and the pathergy test was positive for 28%. Central nervous system (CNS), skin lesions, and gastrointestinal tract involvement were the slightest common manifestations observed in 26%, 25.3%, and 7.3%, respectively. Articular manifestations were markedly linked to skin lesions (P = 0.002), and there was a significant predominance of articular manifestations among females (P = 0.042). BDCAF score was significantly related to male gender (P = 0.037), smokers (P < 0.000), those with older age (P = 0.028), delayed age of disease onset (P = 0.025), and additionally those with the eye (P = 0.000) and CNS involvement (P = 0.003). Conclusion: The clinical features of Egyptian Behçet's patients were significantly dominated by mucocutaneous involvement, followed by ocular affection. Articular manifestations were markedly more significant in women. The disease activity score was more remarkable in males, smokers, those of older age, and those with a delayed age of disease onset.

Enhanced Neuroprotection in Experiment Multiple Sclerosis through Combined Rosiglitazone and Probiotic-Loaded Solid Lipid Nanoparticles: Modulation of Cellular Signaling Pathways.

Multiple sclerosis (MS) is a persistent autoimmune condition characterized by inflammation and neurodegeneration. The current efficacy of treatments is limited, which has generated interest in developing neuroprotective strategies. Solid lipid nanoparticles (SLNs) and probiotics are potential drug delivery vehicles for targeting the CNS (Central nervous system), regulating immune responses, and supporting neuroprotection in neurological conditions. The study investigates how SLNs containing RSG (rosiglitazone) and probiotics can protect the nervous system in cases of MS. We administered toxin EtBr (Ethidium bromide) from day 1 to day 7, later followed by the treatment from day 8 to day 35. During this time interval, various behavioural parameters have been performed. Further, after 35th day, blood plasma of animals was collected to study complete CBC profiling and animals were sacrificed. Then, biochemical and molecular studies, gross morphology of brain sectioning, histopathological evaluation and estimation of fatty acid content in fecal matter were performed. RSG shows neuroprotective effects by blocking the STAT-3 and mTOR signaling pathways and increasing the production of PPAR-gamma. GW9662, a PPAR-gamma antagonist given at a dose of 2 mg/kg (i.p), was utilized to evaluate the role of PPAR-gamma and to compare the efficacy of RSG and probiotic-loaded SLNs in potentially providing neuroprotection. The relationship between RSG and the STAT-3, mTOR, and PPAR-gamma pathways in MS was confirmed and validated using in-silico analysis. RSG and probiotic-loaded SLNs modulate the complete blood profiling of rats and improve the symptoms of MS. We assessed the diagnostic capabilities of different biological samples such as cerebrospinal fluid, blood plasma, and brain homogenates (specifically from the hippocampus, striatum, cortex, and midbrain) to analyze neurochemical changes linked to neurobehavioral changes in the progression of MS. The study showed that combining RSG and probiotics in an experimental medication form improved symptoms of MS more effectively than using RSG alone. This improvement is likely due to changes in STAT-3, mTOR, and PPAR-gamma signaling pathways.

Manifestation of Psychosis and Impairments of Executive Functions Emphasize the Interaction of Psychological and Neurological Dysfunctions in People Who Use Methamphetamine

Aim: Cumulative evidence has demonstrated the neurotoxic effect of methamphetamine (Meth) on the central nervous system. Meth can induce psychotic symptoms and impairments of cognitive abilities, including executive function (EF). Method: In this study, we hypothesized the interaction of the neurotoxic effects of Meth on psychotic symptoms and EF performances. The Stroop test evaluated the EF performances, Go/No-Go task, one-back test (OBT), and Wisconsin Card Sorting Test (WCST) in people who use Meth with psychosis (MWP) and without psychosis (MWOP) compared with healthy control participants. Result: The results showed that MWOP and MWP exhibited EF deficits in attention, working memory, and initial conceptualization. Moreover, a deficit in inhibition was observed in MWOP, while poorer processing speed and cognitive flexibility were found in MWP. Conclusion: The correlation between psychotic symptoms and poor EF performances was observed in MWP. These findings underline the interaction of the mechanistic neurotoxic effect of Meth to induce psychological and neurological dysfunctions in people who use Meth.

L’intoxication au protoxyde d’azote : un nouveau défi pour la biologie médicale

AbstractNitrous oxide (N2O) is a gas used in medicine for its anesthetic and analgesic properties, and in industry as an oxidizing gas or propellant. This gas is also available on self-service for food use. In recent years, its use has been increasingly diverted to recreational purposes. Between 2020 and 2021, the number of serious cases of intoxication increased by 320% in France, demonstrating a major public health concern. It is also a problem for road safety, with an increase in the number of road accidents linked to the consumption of this gas. Nitrous oxide causes both short-term effects (euphoria, disorientation, etc.) and long-term effects (sensory and motor neurological disorders and thrombosis). This gas acts on the central nervous system, inducing anxiolytic, anesthetic, antidepressant and analgesic effects. Nitrous oxide is difficult to quantify because of its rapid elimination. Biological investigation is thus based on secondary anomalies linked to vitamin B12 inactivation: increased methylmalonic acid and homocysteine levels. However, these two biological markers are not specific to nitrous oxide intoxication. To improve patient support, we need to find new biological markers that are more specific to nitrous oxide intoxication.

Multi-target Phenylpropanoids Against Epilepsy.

Epilepsy is a neurological disease with no defined cause, characterized by recurrent epileptic seizures. These occur due to the dysregulation of excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Psychopharmaceuticals have undesirable side effects; many patients require more than one pharmacotherapy to control crises. With this in mind, this work emphasizes the discovery of new substances from natural products that can combat epileptic seizures. Using in silico techniques, this review aims to evaluate the antiepileptic and multi-target activity of phenylpropanoid derivatives. Initially, ligand-based virtual screening models (LBVS) were performed with 468 phenylpropanoid compounds to predict biological activities. The LBVS were developed for the targets alpha- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), voltage-gated calcium channel Ttype (CaV), gamma-aminobutyric acid A (GABAA), gamma-aminobutyric acid transporter type 1 (GAT-1), voltage-gated potassium channel of the Q family (KCNQ), voltage-gated sodium channel (NaV), and N-methyl D-aspartate (NMDA). The compounds that had good results in the LBVS were analyzed for the absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and later, the best molecules were evaluated in the molecular docking consensus. The TR430 compound showed the best results in pharmacokinetic parameters; its oral absorption was 99.03%, it did not violate any Lipinski rule, it showed good bioavailability, and no cytotoxicity was observed either from the molecule or from the metabolites in the evaluated parameters. TR430 was able to bind with GABAA (activation) and AMPA (inhibition) targets and demonstrated good binding energy and significant interactions with both targets. The studied compound showed to be a promising molecule with a possible multi-target activity in both fundamental pharmacological targets for the treatment of epilepsy.

Complex Brain Morphology Discovered in the Shark Parasite Nybelinia surmenicola (Cestoda: Trypanorhyncha).

The ultrastructure of the nervous system has been studied in sexually mature Nybelinia surmenicola (Cestoda: Trypanorhyncha) from the intestine of a shark Lamna ditropis. The central nervous system (CNS) reveals a complex organization within cestodes and corresponds to the trypanorhynch pattern of brain architecture. The brain of N. surmenicola is differentiated into nine clearly defined lobes and semicircular, median, and X-shaped cruciate commissures. A specific feature is the presence of a powerful extracellular capsule that surrounds the brain lobes with the cortical glial cells. Moreover, the architecture of the anterior lobes clearly distinguishes the species of Tentacularioidea. The neurons of the anterior lobes form compact groups looking like frontal horns. There are approximately 120 neurons in the anterior lobes and a preliminary estimate of more than 300 perikarya in the brain. Several ultrastructural types of neurons have been identified, differing in the size and shape of the soma, the density of the cytoplasm, and the ultrastructure of synaptic vesicles. Numerous synapses involving clear and electron-dense vesicles have been observed in neuropils. Two types of glial cells have been found in the brain that participate in neuronal metabolism and wrap around the giant axons, brain lobes, neuropil compartments, and the main nerve cords. Such a powerful extracellular fibrillar brain capsule has not been observed in the brain of other studied cestodes and has been demonstrated in this study for the first time. The differentiation of the brain lobes reveals the important role of the rhyncheal system in the evolution of cestodes and correlates with their behavior. The anterior nerves arising from the anterior lobes innervate the radial muscles stabilizing the position of the tentacle sheaths and movements of the attachment organs. The nervous system anatomy and the brain architecture may reflect the morphofunctional aspects of the tapeworm evolution.

Distinct mechanisms for online and offline motor skill learning across human development.

The human central nervous system (CNS) undergoes tremendous changes from childhood to adulthood and this may affect how individuals at different stages of development learn new skills. Here, we studied motor skill learning in children, adolescents, and young adults to test the prediction that differences in the maturation of different learning mechanisms lead to distinct temporal patterns of motor learning during practice and overnight. We found that overall learning did not differ between children, adolescents, and young adults. However, we demonstrate that adult-like skill learning is characterized by rapid and large improvements in motor performance during practice (i.e., online) that are susceptible to forgetting and decay over time (i.e., offline). On the other hand, child-like learning exhibits slower and less pronounced improvements in performance during practice, but these improvements are robust against forgetting and lead to gains in performance overnight without further practice. The different temporal dynamics of motor skill learning suggest an engagement of distinct learning mechanisms in the human CNS during development. In conclusion, adult-like skill learning mechanisms favor online improvements in motor performance whereas child-like learning mechanisms favors offline behavioral gains. RESEARCH HIGHLIGHTS: Many essential motor skills, like walking, talking, and writing, are acquired during childhood, and it is colloquially thought that children learn better than adults. We investigated dynamics of motor skill learning in children, adolescents, and young adults. Adults displayed substantial improvements during practice that was susceptible to forgetting over time. Children displayed smaller improvements during practice that were resilient against forgetting. The distinct age-related characteristics of these processes of acquisition and consolidation suggest that skill learning relies on different mechanisms in the immature and mature central nervous system.

Dietary Supplements and the Gut–Brain Axis: A Focus on Lemon, Glycerin, and Their Combinations

Dietary supplements are products taken orally, and they contain an ingredient intended to augment the diet. Many studies demonstrate clear alterations in microbe abundances and the production of microbiota-derived metabolites, such as short-chain fatty acids, following dietary changes. This review comprehensively explores the possible interactions among gut microbiota, lemon extracts, glycerin, and their mixture products. Lemon extracts/components are associated with a vast array of health benefits, including anti-inflammation, antioxidant, anti-atherosclerotic, and anti-diabetic effects. They are also associated with increased memory and decreased depression. Glycerin can reduce serum free fatty acids and mimic caloric restriction; its metabolites can function as a broad-spectrum antimicrobial. Additionally, glycerin has a dehydrating effect on the central nervous system and can reduce focal cerebral edema and improve performance by expanding plasma volume. However, it may also have side effects, such as hyperglycemia. Therefore, combined consumption of lemon extracts and glycerin may, in part, mitigate each other’s side effects while exerting their benefits. There is growing evidence that both lemon components and glycerin are metabolized by the gut microbiota and may modulate the intestinal microbiome composition. Therefore, gut microbiome alterations are also explored as an important mechanism in the gut–brain axis regulating various effects of these dietary supplements and their application in various noncommunicable neurological disorders.

Unveiling the hidden culprit: How the brain-gut axis fuels neuroinflammation in ischemic stroke

Background: The brain-gut axis represents a bidirectional communication network between the gut microbiome and the central nervous system that plays an important role in homeostasis. Compelling evidence now confirms that ischemic stroke disrupts this delicate balance by inducing gut dysbiosis. Methods: A comprehensive literature search was performed in PubMed, Web of Science, and Google Scholar for articles published between January 2000 and January 2023 using relevant keywords. Studies were limited to English and included original studies, literature, and systematic reviewers from peer-reviewed journals which discussed gut microbiota composition in models/subjects with ischemic stroke or assessed stroke impact on gut microbiota. Comments, meeting abstracts, and case reports were excluded. From the 80 relevant articles, we summarized key findings related to gut microbiota changes after stroke and their association with stroke outcomes. Results: Emerging preclinical evidence underscores the pivotal role of the gut microbiome in glial cell development and function. Germ-free models exhibit compromised microglial activation and impaired cellular debris clearance, exacerbating tissue damage following ischemic stroke. Targeted interventions, including prebiotics, probiotics, and fecal microbiota transplantation, have demonstrated efficacy in rescuing glial phenotypes in preclinical stroke models. Beyond its local effects, the gut microbiome significantly influences systemic immunity. Ischemic stroke polarizes pro-inflammatory phenotypes of neutrophils and T cells, amplifying neurovascular inflammation. Microbiota manipulation modulates leukocyte trafficking and metabolic signaling, offering potential avenues to mitigate infarct pathology. Conclusion: Our review demonstrates that in preclinical stroke models, modulating the lipopolysaccharide, short-chain fatty acid, and trimethylamine N-oxide pathways through the gut-brain axis reduces infarct sizes and edema and improves functional recovery after ischemic stroke. Further exploration of this important axis may unveil additional adjunctive stroke therapies by elucidating the complex interplay between the microbiome and the brain. Rigorously controlled clinical studies are now warranted to translate these promising preclinical findings and investigate whether manipulating the microbiome-brain relationship can help improve outcomes for stroke patients. Overall, continued research on the gut-brain axis holds exciting possibilities for developing novel treatment strategies that may enhance recovery after stroke.

Nanomedicine as a Better Therapeutic Approach: An Overview

Abstract: The fields of nanotechnology and nanomedicine have undergone a revolution. There has been a striking rise in authorized nanomedicines since 1980. Apart from functioning as thera-peutic agents, they also act as carriers for delivering various active pharmaceuticals to target or-gans. The ultimate goal of nanomedicine has always been the generation of translational technol-ogies that can improve current therapies. Nanocrystals, nanotubes, liposomes, exosomes, solid li-pid nanoparticles, polymeric nanoparticles, and metallic and magnetic nanoparticles are examples of nanostructures that are now in the market as well as in ongoing research. The preparation of these nanomaterials requires consideration of a number of difficulties. Only a few of these nano-materials were successful in obtaining marketing permission after passing all required toxicologi-cal and ethical evaluations and making them affordable to users and, at the same time, profitable to investors. Cancer, central nervous system (CNS) diseases, and cardiovascular (CVS) diseases represented the primary targets of nanotechnology applied to medicine. Therefore, this review ar-ticle is focused on providing a summary of several nano-based delivery systems, including their limitations and prospects in different therapeutic fields.