Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Май 10, 2024

Abstract Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with high risk of psychiatric neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack effective treatments underscore urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as crucial bidirectional pathway connecting gastrointestinal (GI) system through an intricate network neuronal, hormonal, immunological pathways. Four main pathways are primarily implicated this crosstalk, including systemic immune system, autonomic enteric nervous systems, neuroendocrine microbiome. TBI induces profound changes gut, initiating unrestrained vicious cycle that exacerbates axis. Alterations gut include mucosal damage malabsorption nutrients/electrolytes, disintegration intestinal barrier, increased infiltration cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction disruption (ENS) (ANS). Collectively, these further contribute to neuroinflammation neurodegeneration via gut-brain In review article, we elucidate roles various anti-inflammatory pharmacotherapies capable attenuating dysregulated inflammatory response along TBI. These agents hormones such serotonin, ghrelin, progesterone, ANS regulators beta-blockers, lipid-lowering drugs like statins, flora modulators probiotics antibiotics. They attenuate by targeting distinct both post-TBI. exhibit promising potential mitigating inflammation enhancing neurocognitive outcomes patients.

Язык: Английский

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Pathophysiology-Based Management of Secondary Injuries and Insults in TBI

Biomedicines, Год журнала: 2024, Номер 12(3), С. 520 - 520

Опубликована: Фев. 26, 2024

Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality among all ages; despite the advances, understanding pathophysiological responses after TBI is still complex, involving multiple mechanisms. Previous reviews have focused on potential targets; however, research targets has continuously grown in last five years, bringing even more alternatives elucidating previous Knowing key updated pathophysiology concepts vital for adequate management better outcomes. This article underlying molecular mechanisms, latest updates, future directions pathophysiology-based management.

Язык: Английский

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L-Carnitine in the Treatment of Psychiatric and Neurological Manifestations: A Systematic Review

Nutrients, Год журнала: 2024, Номер 16(8), С. 1232 - 1232

Опубликована: Апрель 20, 2024

L-carnitine (LC), a vital nutritional supplement, plays crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application recovery treatment diverse cardiovascular cerebrovascular disorders. However, controversies persist regarding utilization LC nervous system diseases, with varying effects observed across numerous mental neurological This article primarily aims to gather analyze database information comprehensively summarize therapeutic potential patients suffering from diseases while providing valuable references for further research.

Язык: Английский

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CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3788 - 3788

Опубликована: Март 28, 2024

Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge doctors scientists. Injuries lead neuroimmunological changes central (CNS), which may result both secondary development of tactile thermal hypersensitivity. In our review, based on analysis many experimental clinical studies, we indicate that mechanisms occurring at level brain after direct spinal cord peripheral nerve have common immunological basis. This suggests there are opportunities for similar pharmacological therapeutic interventions etiologies. Experimental data CNS/PNS damage, levels 16 among 28 CC-family chemokines, i.e., CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL17, CCL19, CCL20, CCL21, CCL22, increase and/or strong proinflammatory pronociceptive effects. According available literature data, further investigation is needed understanding role remaining especially six them were found humans but not mice/rats, CCL13, CCL14, CCL15, CCL16, CCL18, CCL23. Over past several years, results studies tools used indicated blocking individual receptors, e.g., CCR1 (J113863 BX513), CCR2 (RS504393, CCX872, INCB3344, AZ889), CCR3 (SB328437), CCR4 (C021 AZD-2098), CCR5 (maraviroc, AZD-5672, TAK-220), has beneficial effects CNS PNS. Recently, proved blockades exerted by double antagonists CCR1/3 (UCB 35625) CCR2/5 (cenicriviroc) very good anti-inflammatory antinociceptive addition, single (J113863, RS504393, SB328437, C021, maraviroc) dual chemokine receptor enhanced analgesic effect opioid drugs. review will display evidence multidirectional strategy modulation neuronal–glial–immune interactions can significantly improve health patients PNS changing activity chemokines belonging CC family. Moreover, case pain, combined administration such drugs could reduce doses minimize risk complications.

Язык: Английский

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Inflammatory response in traumatic brain and spinal cord injury: The role of XCL1‐XCR1 axis and T cells

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(6)

Опубликована: Июнь 1, 2024

Abstract Background Traumatic brain injury (TBI) and spinal cord (SCI) are acquired injuries to the central nervous system (CNS) caused by external forces that cause temporary or permanent sensory motor impairments potential for long‐term disability even death. These conditions currently lack effective treatments impose substantial physical, social, economic burdens on millions of people families worldwide. TBI SCI involve intricate pathological mechanisms, inflammatory response contributes significantly secondary in SCI. It plays a crucial role prolonging post‐CNS trauma period becomes focal point therapeutic intervention. Previous research has traditionally concentrated glial cells, such as astrocytes microglia. However, increasing evidence highlights involvement lymphocytes CNS injury, particularly CD8 + T cells NK along with their downstream XCL1‐XCR1 axis. Objective This review aims provide an overview axis T‐cell inflammation identify targets therapy. Methods We conducted comprehensive search PubMed Web Science using relevant keywords related axis, response, TBI, Results study examines upstream pathways involved SCI, including interleukin‐15 (IL‐15), interleukin‐12 (IL‐12), CD4 XCL1, XCR1 dendritic interferon‐gamma (IFN‐γ), helper T0 (Th0 cells), T1 (Th1 T17 (Th17 cells). describe proinflammatory effect Conclusions The findings suggest have great preclinical investigations

Язык: Английский

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Significance of Programmed Cell Death Pathways in Neurodegenerative Diseases

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 9947 - 9947

Опубликована: Сен. 15, 2024

Programmed cell death (PCD) is a form of distinct from accidental (ACD) and also referred to as regulated (RCD). Typically, PCD signaling events are precisely by various biomolecules in both spatial temporal contexts promote neuronal development, establish neural architecture, shape the central nervous system (CNS), although role extends beyond CNS. Abnormalities cascades contribute irreversible loss cells function, leading onset progression neurodegenerative diseases. In this review, we summarize molecular processes features different modalities PCD, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, other novel forms their effects on pathogenesis diseases, such Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), multiple (MS), traumatic brain injury (TBI), stroke. Additionally, examine key factors involved these pathways discuss potential for development therapeutic targets strategies. Therefore, strategies targeting inhibition or facilitation offer promising approach clinical applications treating

Язык: Английский

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Mapping Inflammatory Markers in Cerebrospinal Fluid Following Aneurysmal Subarachnoid Hemorrhage: An Age- and Sex-Matched Analysis

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1302 - 1302

Опубликована: Фев. 3, 2025

Despite extensive research on aneurysm treatment and neurocritical care, aneurysmal subarachnoid hemorrhage (SAH) is still a life-threatening disease, often leaving survivors with lasting neurological cognitive impairments. Early brain injury (EBI) delayed cerebral ischemia (DCI) are the main contributors to damage, neuroinflammation being critical shared pathophysiological process. While numerous inflammatory markers their temporal profiles in cerebrospinal fluid (CSF) have already been identified, comparisons age- sex-matched controls limited. This study analyzed CSF from 17 SAH patients requiring an external ventricular drain (EVD) due symptomatic hydrocephalus, sampled days 4 10 post-ictus. An control group included cerebrovascularly healthy lumbar drains during aortic surgery. Chemokines cytokines were quantified using immunoassays. Significantly elevated across both time points MCP-1, CXCL-13, Eotaxin-1, CXCL-10, IL-8, MIF. MIP-1α MIP-1β showed significant differences at particular points, indicating distinct profile for each parameter. These findings highlight neuroinflammation’s key role intracranial systemic pathophysiology following SAH, emphasizing its complexity individual variability. Knowing demographic factors impact specific manifestations of processes, comparison meaningful.

Язык: Английский

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Physical activity and neuroplasticity in neurodegenerative disorders: a comprehensive review of exercise interventions, cognitive training, and AI applications

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Фев. 28, 2025

This review aimed to elucidate the mechanisms through which (i) physical activity (PA) enhances neuroplasticity and cognitive function in neurodegenerative disorders, (ii) identify specific PA interventions for improving rehabilitation programs. We conducted a literature search PubMed, Medline, Scopus, Web of Science, PsycINFO, covering publications from January 1990 August 2024. The strategy employed key terms related neuroplasticity, exercise, function, personalized activity. Inclusion criteria included original research on relationship between while exclusion eliminated studies focusing solely pharmacological interventions. identified multiple pathways may enhance including releasing neurotrophic factors, modulation neuroinflammation, reduction oxidative stress, enhancement synaptic connectivity neurogenesis. Aerobic exercise was found increase hippocampal volume by 1–2% improve executive scores 5–10% older adults. Resistance training enhanced control memory performance 12–18% elderly individuals. Mind–body exercises, such as yoga tai-chi, improved gray matter density memory-related brain regions 3–5% emotional regulation 15–20%. Dual-task attention processing speed 8–14% individuals with disorders. also discuss potential role AI-based AI preventing rehabilitating illnesses, highlighting innovative approaches patient outcomes. significantly disorders various mechanisms. resistance training, mind–body practices, dual-task exercises each offer unique benefits. Implementing these activities clinical settings can Future should focus creating tailored conditions, incorporating programs optimize rehabilitation.

Язык: Английский

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Immune Regulatory Functions of Macrophages and Microglia in Central Nervous System Diseases

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5925 - 5925

Опубликована: Март 21, 2023

Macrophages can be characterized as a very multifunctional cell type with spectrum of phenotypes and functions being observed spatially temporally in various disease states. Ample studies have now demonstrated possible causal link between macrophage activation the development autoimmune disorders. How these cells may contributing to adaptive immune response potentially perpetuating progression neurodegenerative diseases neural injuries is not fully understood. Within this review, we hope illustrate role that macrophages microglia play initiators CNS by offering evidence of: (1) types responses processes antigen presentation each disease, (2) receptors involved macrophage/microglial phagocytosis disease-related debris or molecules, and, finally, (3) implications macrophages/microglia on pathogenesis diseases.

Язык: Английский

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Role of Sirtuin 3 in Degenerative Diseases of the Central Nervous System

Biomolecules, Год журнала: 2023, Номер 13(5), С. 735 - 735

Опубликована: Апрель 24, 2023

An NAD+-dependent deacetylase called Sirtuin 3 (Sirt3) is involved in the metabolic processes of mitochondria, including energy generation, tricarboxylic acid cycle, and oxidative stress. Sirt3 activation can slow down or prevent mitochondrial dysfunction response to neurodegenerative disorders, demonstrating a strong neuroprotective impact. The mechanism illnesses has been elucidated over time; it essential for neuron, astrocyte, microglial function, its primary regulatory factors include antiapoptosis, stress, maintenance homeostasis. Neurodegenerative such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), amyotrophic lateral sclerosis (ALS), multiple (MS), may benefit from thorough in-depth investigation Sirt3. In this review, we primarily cover Sirt3’s role regulation nerve cells connection between disorders.

Язык: Английский

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