Astrocytes in human central nervous system diseases: a frontier for new therapies

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Окт. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Язык: Английский

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Understanding Acquired Brain Injury: A Review

Biomedicines, Год журнала: 2022, Номер 10(9), С. 2167 - 2167

Опубликована: Сен. 2, 2022

Any type of brain injury that transpires post-birth is referred to as Acquired Brain Injury (ABI). In general, ABI does not result from congenital disorders, degenerative diseases, or by trauma at birth. Although the human protected external world layers tissues and bone, floating in nutrient-rich cerebrospinal fluid (CSF); it remains susceptible harm impairment. damage resulting leads changes normal neuronal tissue activity and/or structure one multiple areas brain, which can often affect functions. Impairment sustained an last anywhere days a lifetime depending on severity injury; however, many patients face trouble integrating themselves back into community due possible psychological physiological outcomes. this review, we discuss pathologies, their types, cellular mechanisms summarize therapeutic approaches for better understanding subject create awareness among public.

Язык: Английский

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Cellular and Molecular Pathophysiology of Traumatic Brain Injury: What Have We Learned So Far?

Biology, Год журнала: 2023, Номер 12(8), С. 1139 - 1139

Опубликована: Авг. 17, 2023

Traumatic brain injury (TBI) is one of the leading causes long-lasting morbidity and mortality worldwide, being a devastating condition related to impairment nervous system after an external traumatic event resulting in transitory or permanent functional disability, with significant burden healthcare system. Harmful events underlying TBI can be classified into two sequential stages, primary secondary, which are both associated breakdown tissue homeostasis due blood–brain barrier, osmotic imbalance, inflammatory processes, oxidative stress, excitotoxicity, apoptotic cell death, ultimately loss functionality. The present study provides updated review concerning roles edema, inflammation, stress on changes from TBI. proper characterization phenomena contribute improvement care, rehabilitation quality life affected people.

Язык: Английский

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Reactive gliosis in traumatic brain injury: a comprehensive review

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Фев. 28, 2024

Traumatic brain injury (TBI) is one of the most common pathological conditions impacting central nervous system (CNS). A neurological deficit associated with TBI results from a complex pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or development edema. The critical components contributing to CNS response, damage control, and regeneration after are glial cells–in reaction tissue damage, their activation, hypertrophy, proliferation occur, followed by formation scar. scar creates barrier in damaged helps protect acute phase post-injury. However, this process prevents complete recovery late/chronic producing permanent scarring, which significantly impacts function. Various types participate formation, but mostly attributed reactive astrocytes microglia, play important roles several pathologies. Novel technologies whole-genome transcriptomic epigenomic analyses, unbiased proteomics, show that both microglia represent groups heterogenic subpopulations different genomic functional characteristics, responsible for role neurodegeneration, neuroprotection regeneration. Depending on representation distinct glia subpopulations, as well regenerative processes delayed neurodegeneration may thus differ nearby remote areas structures. This review summarizes process, where resultant effect severity-, region- time-dependent determined model distance explored area lesion site. Here, we also discuss findings concerning intercellular signaling, long-term possibilities novel therapeutical approaches. We believe comprehensive study an emphasis cells, involved post-injury processes, be helpful further research decisive factor when choosing model.

Язык: Английский

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Applications of hydrogels and nanoparticles in the treatment of traumatic brain injury

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 12

Опубликована: Янв. 6, 2025

Traumatic brain injury (TBI) represents a significant global public health issue, with effective management posing numerous challenges. The pathophysiology of TBI is typically categorized into two phases: primary and secondary injuries. Secondary involves pathophysiological mechanisms such as blood-brain barrier (BBB) disruption, mitochondrial dysfunction, oxidative stress, inflammatory responses. Current pharmacological strategies often encounter obstacles in treating effectively, primarily due to challenges BBB penetration, inadequate target site accumulation, off-target toxicity. Versatile hydrogels nanoparticles offer potential solutions these limitations. This review discusses recent progress utilizing for treatment over the past 5 years, highlighting their relevance underlying pathophysiology. Hydrogels demonstrate substantial promise addressing injury, providing broad spectrum future therapeutic opportunities.

Язык: Английский

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Neuroinflammation Following Traumatic Brain Injury: Take It Seriously or Not

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Март 22, 2022

Traumatic brain injury (TBI) is associated with high mortality and disability, a substantial socioeconomic burden. With the standardization of treatment process, there increasing interest in role that secondary insult TBI plays outcome heterogeneity. The neither detrimental nor beneficial an absolute sense, among which inflammatory response was complex cascade events can thus be regarded as double-edged sword. Therefore, clinicians should take generation balance neuroinflammation following seriously. In this review, we summarize current human animal model studies provide better understanding different stages TBI. particular, advances using proteomic transcriptomic techniques have enabled us to identify functional specific delineation immune cell patients. Based on recent our activation, present difference between diffuse axonal focal injury. addition, give figurative profiling general paradigm pre- post-injury settings employing bow-tie framework.

Язык: Английский

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N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1268 - 1268

Опубликована: Янв. 23, 2022

N-acetyl-aspartyl-glutamate (NAAG) is the most abundant dipeptide in brain, where it acts as a neuromodulator of glutamatergic synapses by activating presynaptic metabotropic glutamate receptor 3 (mGluR3). Recent data suggest that NAAG selectively localized to postsynaptic dendrites and works retrograde neurotransmitter. released response provides neuron with feedback mechanisms inhibit excessive signaling. A key regulator synaptically available rapid degradation extracellular enzyme carboxypeptidase II (GCPII). Increasing endogenous NAAG-for instance inhibiting GCPII-is promising treatment option for many brain disorders excitotoxicity plays role. The main effect occurs through increased mGluR3 activation thereby reduced release. In present review, we summarize transmitter role discuss involvement normal physiology. We further suggested roles various neurological psychiatric diseases therapeutic potential strategies aiming enhance levels.

Язык: Английский

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Immune modulation after traumatic brain injury

Frontiers in Medicine, Год журнала: 2022, Номер 9

Опубликована: Дек. 1, 2022

Traumatic brain injury (TBI) induces instant activation of innate immunity in tissue, followed by a systematization the inflammatory response. The subsequent response, evolved to limit an overwhelming systemic response and induce healing, involves autonomic nervous system, hormonal systems, regulation immune cells. This physiological immunosuppression tolerance state that promotes occurrence secondary infections. review describes immunological consequences TBI highlights potential novel therapeutic approaches using modulation restore homeostasis between system immunity.

Язык: Английский

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Loading neural stem cells on hydrogel scaffold improves cell retention rate and promotes functional recovery in traumatic brain injury

Materials Today Bio, Год журнала: 2023, Номер 19, С. 100606 - 100606

Опубликована: Март 8, 2023

Neural stem cell (NSC) has gained considerable attention in traumatic brain injury (TBI) treatment because of their ability to replenish dysfunctional neurons and stimulate endogenous neurorestorative processes. However, therapeutic effects are hindered by the low retention rate after transplantation into dynamic brain. In this study, we found cerebrospinal fluid (CSF) flow TBI is an important factor associated with loss following NSC transplantation. Recently, several studies have shown that hydrogels could serve as a beneficial carrier for transplantation, which provides solution prevent CSF flow-induced TBI. For purpose, evaluated three different hydrogel scaffolds gelatin methacrylate (GelMA)/sodium alginate (Alg) (GelMA/Alg) scaffold showed best capabilities adherence, growth, differentiation. Additionally, detected pre-differentiated NSCs, were loaded on GelMA/Alg cultured 7 days neuronal differentiation medium (NSC [7d]), had highest impact. Next, neuroprotective NSC-loaded rat model [7d]-loaded markedly decreased microglial activation death acute phase, reduced tissue loss, alleviated astrogliosis, promoted neurogenesis, improved neurological recovery chronic phase. summary, demonstrated integration modification inhibit influence transplanted leading increased number retained NSCs effects, providing promising alternative treatment.

Язык: Английский

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Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 3, 2024

Traumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability the development of secondary neurodegenerative diseases. A holistic understanding mechanisms controlling responses specific types their crosstalk is required develop an efficient strategy better regeneration. Here, we combine spatial single-cell transcriptomics chart transcriptomic signature injured male murine cerebral cortex, identify states different cells contributing this signature. Interestingly, distinct share large fraction injury-regulated genes, including inflammatory programs downstream innate immune-associated pathways Cxcr3 Tlr1/2. Systemic manipulation these decreases reactivity state associated with poor The functional relevance discovered shared highlights importance our resource enabling comprehensive analysis early events after injury.

Язык: Английский

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