Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 148 - 148

Published: Jan. 12, 2024

Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents central nervous system (CNS), in both pathophysiology and possible rehabilitation TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) neuroprotective (A2) phenotypes. paper elucidates interactions with neurons, their role neuroinflammation, potential for exploitation. Emphasized strategies encompass utilization endocannabinoid calcium signaling pathways, hormone-based treatments like 17β-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, innovative technique astrocyte transplantation as means to repair damaged neural tissues.

Language: Английский

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The Role of Lipids, Lipid Metabolism and Ectopic Lipid Accumulation in Axon Growth, Regeneration and Repair after CNS Injury and Disease

Cells, Journal Year: 2021, Volume and Issue: 10(5), P. 1078 - 1078

Published: May 1, 2021

Axons in the adult mammalian nervous system can extend over formidable distances, up to one meter or more humans. During development, axonal and dendritic growth requires continuous addition of new membrane. Of three major kinds membrane lipids, phospholipids are most abundant all cell membranes, including neurons. Not only immature axons, but also severed axons require large amounts lipids for axon regeneration occur. Lipids serve as energy storage, signaling molecules they contribute tissue physiology, demonstrated by a variety metabolic disorders which harmful accumulate various tissues through body. Detrimental changes lipid metabolism excess accumulation lack regeneration, poor neurological outcome complications after central (CNS) trauma brain spinal cord injury. Recent evidence indicates that rewiring be manipulated therapeutic gain, it favors conditions CNS repair. Here, we review role ectopic growth, In addition, outline molecular pharmacological strategies fine-tune composition neurons non-neuronal cells exploited improve recovery disease.

Language: Английский

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Injury distance limits the transcriptional response to spinal injury

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Abstract The ability of neurons to sense and respond damage is fundamental homeostasis nervous system repair. For some cell types, notably dorsal root ganglia (DRG) retinal ganglion cells (RGCs), extensive profiling has revealed a large transcriptional response axon injury that determines survival regenerative outcomes. In contrast, the most supraspinal whose limited regeneration constrains recovery from spinal injury, mostly unknown. Here we employed single-nuclei sequencing in mice profile responses diverse types injury. Surprisingly, thoracic triggered only modest changes gene expression across all populations, including corticospinal tract (CST) neurons. Moreover, CST also responded minimally cervical but much more strongly intracortical axotomy, upregulation numerous apoptosis-related transcripts shared with injured DRG RGC Thus, muted neuron linked injury’s distal location, rather than intrinsic cellular characteristics. More broadly, these findings indicate central challenge for enhancing after sensing distant injuries subsequent baseline neuronal response.

Language: Английский

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Axonal Organelles as Molecular Platforms for Axon Growth and Regeneration after Injury

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 1798 - 1798

Published: Feb. 11, 2021

Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies boosting regeneration after injury, with goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that various axonal organelles are important centers organizing machinery required cone development extension, these have recently targeted to stimulate robust in injured adult central nervous system (CNS). This review summarizes recent literature highlighting role recycling endosomes, endoplasmic reticulum, mitochondria, lysosomes, autophagosomes proteasome growth, describes how can be promote CNS. also examines connections between developing regenerating axons, finally discusses within successful growth.

Language: Английский

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Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling

Neural Regeneration Research, Journal Year: 2021, Volume and Issue: 17(6), P. 1172 - 1172

Published: Nov. 17, 2021

Much research has focused on the PI3-kinase and PTEN signaling pathway with aim to stimulate repair of injured central nervous system. Axons in system fail regenerate, meaning that injuries or diseases cause loss axonal connectivity have life-changing consequences. In 2008, genetic deletion was identified as a means stimulating robust regeneration optic nerve. is phosphatase opposes actions PI3-kinase, family enzymes function generate membrane phospholipid PIP3 from PIP2 (phosphatidylinositol (3,4,5)-trisphosphate phosphatidylinositol (4,5)-bisphosphate). Deletion therefore allows elevated downstream initially demonstrated promote axon by through mTOR. More recently, additional mechanisms been contribute neuron-intrinsic control regenerative ability. This review describes neuronal pathways PIP3, considers them relation both developmental growth. We briefly discuss key govern ability, describe how these are affected PI3-kinase. highlight recent finding decline generation reason for failure, summarize studies target an increase facilitate adult Finally, we obstacles remain be overcome order strategy repairing manipulation signaling.

Language: Английский

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Functional and Structural Changes in the Inner Ear and Cochlear Hair Cell Loss Induced by Hypergravity

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 758 - 758

Published: Jan. 17, 2025

Gravitational changes have been shown to cause significant abnormalities in various body systems, including the cardiovascular, immune, vestibular, and musculoskeletal systems. While numerous studies examined response of vestibular system gravitational stimulation, research on functional peripheral inner ear remains limited. The comprises two closely related structures: vestibule cochlea. These components share similar structures neural functions, highlighting importance investigating auditory nerve cells alterations. To address this gap, we studied structural following exposure hypergravity stimuli. Our findings demonstrate brainstem responses (ABRs) ABR recordings were used analyze click thresholds, as well amplitude latency tone bursts. thresholds at all frequencies increased group exposed long term. Additionally, burst results revealed significantly reduced amplitudes high delayed latencies models. Notably, greater hair cell loss was observed middle basal turns cochlea, indicating that mid high-frequency regions are more vulnerable stimulation. Furthermore, damage cochlear surface evident subjects 4G stimulation for 4 weeks. suggest its activity can be functionally structurally affected by prolonged hypergravity.

Language: Английский

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Additive manufacturing in spatial patterning for spinal cord injury treatment

Advanced Drug Delivery Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 115523 - 115523

Published: Jan. 1, 2025

Language: Английский

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Multiplexed CRISPRi Reveals a Transcriptional Switch Between KLF Activators and Repressors in the Maturing Neocortex

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Abstract A critical phase of mammalian brain development takes place after birth. Neurons the mouse neocortex undergo dramatic changes in their morphology, physiology, and synaptic connections during first postnatal month, while properties immature neurons, such as capacity for robust axon outgrowth, are lost. The genetic epigenetic programs controlling prenatal well studied, but our understanding transcriptional mechanisms that regulate neuronal maturation is comparatively lacking. By integrating chromatin accessibility gene expression data from two subtypes neocortical pyramidal neurons neonatal maturing brain, we predicted a role Krüppel-Like Factor (KLF) family Transcription Factors developmental regulation neonatally expressed genes. Using multiplexed CRISPR Interference (CRISPRi) knockdown strategy, found shift KLF activators (Klf6, Klf7) to repressors (Klf9, Klf13) early functions ‘switch’ activate, then repress set shared targets with cytoskeletal including Tubb2b Dpysl3 . We demonstrate this switch buffered by redundancy between paralogs, which CRISPRi strategy equipped overcome study. Our results indicate competition within regulates conserved component program may underlie loss intrinsic growth neurons. This could facilitate transition refinement required stabilize mature circuits.

Language: Английский

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Multiplexed CRISPRi Reveals a Transcriptional Switch Between KLF Activators and Repressors in the Maturing Neocortex

Published: April 30, 2025

A critical phase of mammalian brain development takes place after birth. Neurons the mouse neocortex undergo dramatic changes in their morphology, physiology, and synaptic connections during first postnatal month, while properties immature neurons, such as capacity for robust axon outgrowth, are lost. The genetic epigenetic programs controlling prenatal well studied, but our understanding transcriptional mechanisms that regulate neuronal maturation is comparatively lacking. By integrating chromatin accessibility gene expression data from two subtypes neocortical pyramidal neurons neonatal maturing brain, we predicted a role Krüppel-Like Factor (KLF) family Transcription Factors developmental regulation neonatally expressed genes. Using multiplexed CRISPR Interference (CRISPRi) knockdown strategy, found shift KLF activators (Klf6, Klf7) to repressors (Klf9, Klf13) early functions ‘switch’ activate, then repress set shared targets with cytoskeletal including Tubb2b Dpysl3 . We demonstrate this switch buffered by redundancy between paralogs, which CRISPRi strategy equipped overcome study. Our results indicate competition within regulates conserved component program may underlie loss intrinsic growth neurons. This could facilitate transition refinement required stabilize mature circuits.

Language: Английский

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Multiplexed CRISPRi Reveals a Transcriptional Switch Between KLF Activators and Repressors in the Maturing Neocortex

Published: April 30, 2025

A critical phase of mammalian brain development takes place after birth. Neurons the mouse neocortex undergo dramatic changes in their morphology, physiology, and synaptic connections during first postnatal month, while properties immature neurons, such as capacity for robust axon outgrowth, are lost. The genetic epigenetic programs controlling prenatal well studied, but our understanding transcriptional mechanisms that regulate neuronal maturation is comparatively lacking. By integrating chromatin accessibility gene expression data from two subtypes neocortical pyramidal neurons neonatal maturing brain, we predicted a role Krüppel-Like Factor (KLF) family Transcription Factors developmental regulation neonatally expressed genes. Using multiplexed CRISPR Interference (CRISPRi) knockdown strategy, found shift KLF activators (Klf6, Klf7) to repressors (Klf9, Klf13) early functions ‘switch’ activate, then repress set shared targets with cytoskeletal including Tubb2b Dpysl3 . We demonstrate this switch buffered by redundancy between paralogs, which CRISPRi strategy equipped overcome study. Our results indicate competition within regulates conserved component program may underlie loss intrinsic growth neurons. This could facilitate transition refinement required stabilize mature circuits.

Language: Английский

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