Traumatic brain injury: Mechanisms, manifestations, and visual sequelae

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Feb. 23, 2023

Traumatic brain injury (TBI) results when external physical forces impact the head with sufficient intensity to cause damage brain. TBI can be mild, moderate, or severe and may have long-term consequences including visual difficulties, cognitive deficits, headache, pain, sleep disturbances, post-traumatic epilepsy. Disruption of normal functioning leads a cascade effects molecular anatomical changes, persistent neuronal hyperexcitation, neuroinflammation, loss. Destructive processes that occur at cellular level lead inflammation, oxidative stress, calcium dysregulation, apoptosis. Vascular damage, ischemia loss blood barrier integrity contribute destruction tissue. This review focuses on incited during frequently life-altering lasting this vision, cognition, balance, sleep. The wide range complaints associated are addressed repair where there is potential for intervention preservation highlighted.

Language: Английский

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TGF-β as a Key Modulator of Astrocyte Reactivity: Disease Relevance and Therapeutic Implications

Biomedicines, Journal Year: 2022, Volume and Issue: 10(5), P. 1206 - 1206

Published: May 23, 2022

Astrocytes are essential for normal brain development and functioning. They respond to injury disease through a process referred as reactive astrogliosis, where the reactivity is highly heterogenous context-dependent. Reactive astrocytes active contributors pathology can exert beneficial, detrimental, or mixed effects following insults. Transforming growth factor-β (TGF-β) has been identified one of key factors regulating astrocyte reactivity. The genetic pharmacological manipulation TGF-β signaling pathway in animal models central nervous system (CNS) alters pathological functional outcomes. This review aims provide recent understanding regarding injury, aging, neurodegeneration. Further, it explores how modulates function context CNS injury.

Language: Английский

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Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders

Cells, Journal Year: 2022, Volume and Issue: 11(7), P. 1139 - 1139

Published: March 28, 2022

Several neurodegenerative disorders involve impaired neurotransmission, and glutamatergic neurotransmission sets a prototypical example. Glutamate is predominant excitatory neurotransmitter where the astrocytes play pivotal role in maintaining extracellular levels through release uptake mechanisms. Astrocytes modulate calcium-mediated excitability several neurotransmitters neuromodulators, including glutamate, significantly neurotransmission. Accumulating evidence supports concept of excitotoxicity caused by astrocytic pathological conditions. Thus, current review highlights different vesicular non-vesicular mechanisms glutamate their implication diseases. As presynaptic neurons, also primarily meditated exocytosis. V-ATPase crucial acidification maintenance gradient that facilitates storage glutamate. Along with these, other components, such as cystine/glutamate antiporter, hemichannels, BEST-1, TREK-1, purinergic receptors so forth, contribute to under physiological Events hampered could promote inflamed trigger repetitive This be favorable towards development worsening Therefore, across diseases, we relations between defective signaling events homeostasis. The optimum regulation transmission pave way for management these diseases add therapeutic value.

Language: Английский

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Reactive astrogliosis in the era of single-cell transcriptomics

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: April 20, 2023

Reactive astrogliosis is a reaction of astrocytes to disturbed homeostasis in the central nervous system (CNS), accompanied by changes astrocyte numbers, morphology, and function. are important onset progression many neuropathologies, such as neurotrauma, stroke, neurodegenerative diseases. Single-cell transcriptomics has revealed remarkable heterogeneity reactive astrocytes, indicating their multifaceted functions whole spectrum with temporal spatial resolution, both brain spinal cord. Interestingly, transcriptomic signatures partially overlap between neurological diseases, suggesting shared unique gene expression patterns response individual neuropathologies. In era single-cell transcriptomics, number new datasets steeply increases, they often benefit from comparisons integration previously published work. Here, we provide an overview populations defined or single-nucleus across multiple attempting facilitate search for relevant reference points improve interpretability containing cells astrocytes.

Language: Английский

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Astrocyte Involvement in Blood–Brain Barrier Function: A Critical Update Highlighting Novel, Complex, Neurovascular Interactions

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17146 - 17146

Published: Dec. 5, 2023

Neurological disorders have been linked to a defective blood–brain barrier (BBB), with dysfunctions triggered by stage-specific disease mechanisms, some of these being generated through interactions in the neurovascular unit (NVU). Advanced knowledge molecular and signaling mechanisms NVU emergence improved experimental models allow BBB permeability prediction development new brain-targeted therapies. As constituents, astrocytes are most numerous glial cells, characterized heterogeneity that occurs as result developmental context-based gene expression profiles differential non-coding ribonucleic acids (RNAs). Due their dynamic responses different signals, may beneficial or detrimental role BBB’s function, deep effects on pathophysiology (and progression of) central nervous system diseases. The implication astrocytic-derived extracellular vesicles pathological due ability pass BBB, must also be considered. astrocytes’ interaction endothelial cells at level considered promising therapeutic targets neurological conditions. Nevertheless, personalized well-founded approach addressed, temporal spatial reactive astrogliosis states during disease.

Language: Английский

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Human early-onset dementia caused by DAP12 deficiency reveals a unique signature of dysregulated microglia

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(3), P. 545 - 557

Published: Jan. 19, 2023

Language: Английский

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Microglia and Astroglia—The Potential Role in Neuroinflammation Induced by Pre- and Neonatal Exposure to Lead (Pb)

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 9903 - 9903

Published: June 8, 2023

Neuroinflammation is one of the postulated mechanisms for Pb neurotoxicity. However, exact molecular responsible its pro-inflammatory effect are not fully elucidated. In this study, we examined role glial cells in neuroinflammation induced by exposure. We investigated how microglia, a type cell, responded to changes caused perinatal exposure measuring expression Iba1 at mRNA and protein levels. To assess state analyzed levels specific markers associated with cytotoxic M1 phenotype (Il1b, Il6, Tnfa) cytoprotective M2 (Arg1, Chi3l1, Mrc1, Fcgr1a, Sphk1, Tgfb1). Additionally, measured concentration cytokines (IL-1β, IL-6, TNF-α). reactivity functionality status astrocytes, GFAP (mRNA concentration) as well glutamine synthase (GS) level activity. Using an electron microscope, assessed ultrastructural abnormalities brain structures (forebrain cortex, cerebellum, hippocampus). addition, Cxcl1 Cxcl2, their receptor, Cxcr2. Our data showed that low doses affected both microglia astrocyte cells’ (their mobilization, activation, function, gene profile) brain-structure-specific manner. The results suggest astrocytes represent potential target neurotoxicity, thus being key mediators further neuropathology evoked poisoning during development.

Language: Английский

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Astrocytic Neuroimmunological Roles Interacting with Microglial Cells in Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1599 - 1599

Published: Jan. 13, 2023

Both astrocytic and microglial functions have been extensively investigated in healthy subjects neurodegenerative diseases. For astrocytes, not only various sub-types were identified but phagocytic activity was also clarified recently is making dramatic progress. In this review paper, we mostly focus on the functional role of astrocytes extracellular matrix interactions between reactive microglia normal states diseases, because authors feel it necessary to elucidate mechanisms among activated glial cells pathology neurological diseases order pave way for drug discovery. Finally, will cyclic phosphatidic acid (cPA), a naturally occurring phospholipid mediator that induces variety biological activities brain both vivo vitro. We propose cPA may serve as novel therapeutic molecule treatment injury neuroinflammation.

Language: Английский

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Stroke Related Brain–Heart Crosstalk: Pathophysiology, Clinical Implications, and Underlying Mechanisms

Advanced Science, Journal Year: 2024, Volume and Issue: 11(14)

Published: Feb. 2, 2024

Abstract The emergence of acute ischemic stroke (AIS) induced cardiovascular dysfunctions as a bidirectional interaction has gained paramount importance in understanding the intricate relationship between brain and heart. Post AIS, ensuing encompass spectrum complications, including heart attack, congestive failure, systolic or diastolic dysfunction, arrhythmias, electrocardiographic anomalies, hemodynamic instability, cardiac arrest, among others, all which are correlated with adverse outcomes mortality. Mounting evidence underscores intimate crosstalk brain, facilitated by physiological neurohumoral complex networks. primary pathophysiological mechanisms contributing to these severe complications involve hypothalamic‐pituitary‐adrenal (HPA) axis, sympathetic parasympathetic hyperactivity, immune inflammatory responses, gut dysbiosis, collectively shaping stroke‐related brain–heart axis. Ongoing research endeavors concentrated on devising strategies prevent AIS‐induced dysfunctions. Notably, labetalol, nicardipine, nitroprusside recommended for hypertension control, while β‐blockers employed avert chronic remodeling address arrhythmias. However, despite therapeutic interventions, targets remain elusive, necessitating further investigations into this challenge. This review aims delineate state‐of‐the‐art AIS through preclinical clinical research, unraveling their interplay within offering pragmatic suggestions managing

Language: Английский

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Selenium Nanoparticles in Protecting the Brain from Stroke: Possible Signaling and Metabolic Mechanisms

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(2), P. 160 - 160

Published: Jan. 11, 2024

Strokes rank as the second most common cause of mortality and disability in human population across world. Currently, available methods treating or preventing strokes have significant limitations, primarily need to use high doses drugs due presence blood-brain barrier. In last decade, increasing attention has been paid capabilities nanotechnology. However, vast majority research this area is focused on mechanisms anticancer antiviral effects nanoparticles. our opinion, not enough neuroprotective nanomaterials. review, we attempted summarize key molecular brain cell damage during ischemia. We discussed current literature regarding various nanomaterials for treatment strokes. examined features all known nanomaterials, possibility which are currently being studied regard, positive negative properties identified. Particular review was nanoselenium since selenium a vital microelement part very important little-studied proteins, e.g., selenoproteins selenium-containing proteins. An analysis modern studies cytoprotective made it possible establish acute chronic protective aimed combine information action nanoparticles neurodegenerative processes, especially cerebral

Language: Английский

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