Spinal cord injury: molecular mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 26, 2023

Abstract Spinal cord injury (SCI) remains a severe condition with an extremely high disability rate. The challenges of SCI repair include its complex pathological mechanisms and the difficulties neural regeneration in central nervous system. In past few decades, researchers have attempted to completely elucidate mechanism identify effective strategies promote axon circuit remodeling, but results not been ideal. Recently, new SCI, especially interactions between immune cell responses, revealed by single-cell sequencing spatial transcriptome analysis. With development bioactive materials stem cells, more attention has focused on forming intermediate networks reconstruction than promoting axonal corticospinal tract. Furthermore, technologies control physical parameters such as electricity, magnetism ultrasound constantly innovated applied fate regulation. Among these advanced novel technologies, therapy, biomaterial transplantation, electromagnetic stimulation entered into stage clinical trials, some them already treatment. this review, we outline overall epidemiology pathophysiology expound latest research progress related detail, propose future directions for applications.

Language: Английский

---

Generalized fear after acute stress is caused by change in neuronal cotransmitter identity

Science, Journal Year: 2024, Volume and Issue: 383(6688), P. 1252 - 1259

Published: March 14, 2024

Overgeneralization of fear to harmless situations is a core feature anxiety disorders resulting from acute stress, yet the mechanisms by which becomes generalized are poorly understood. In this study, we show that in mice results transmitter switch glutamate γ-aminobutyric acid (GABA) serotonergic neurons lateral wings dorsal raphe. Similar change identity was found postmortem brains individuals with posttraumatic stress disorder (PTSD). Overriding prevented acquisition fear. Corticosterone release and activation glucocorticoid receptors mediated switch, prompt antidepressant treatment blocked cotransmitter Our provide important insight into involved generalization.

Language: Английский

---

Multimodal therapy strategy based on a bioactive hydrogel for repair of spinal cord injury

Biomaterials, Journal Year: 2023, Volume and Issue: 299, P. 122160 - 122160

Published: May 11, 2023

Language: Английский

---

A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: June 9, 2023

Abstract Spinal cord injury (SCI) is a devastating and disabling medical condition generally caused by traumatic event (primary injury). This initial trauma accompanied set of biological mechanisms directed to ameliorate neural damage but also exacerbate (secondary The alterations that occur in the spinal have not only local systemic consequences virtually all organs tissues body incur important changes after SCI, explaining progression detrimental related this condition. Psychoneuroimmunoendocrinology (PNIE) growing area research aiming integrate explore interactions among different systems compose human organism, considering mind as whole. consequent neurological disruption trigger immune, endocrine, multisystem dysfunction, which turn affect patient’s psyche well-being. In present review, we will most SCI from PNIE perspective, defining occurring each system how these are interconnected. Finally, potential clinical approaches derived knowledge be collectively presented with aim develop integrative therapies maximize management patients.

Language: Английский

---

Changes in intra‐ and interlimb reflexes from hindlimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats

The Journal of Physiology, Journal Year: 2024, Volume and Issue: 602(9), P. 1987 - 2017

Published: April 9, 2024

Abstract When the foot dorsum contacts an obstacle during locomotion, cutaneous afferents signal central circuits to coordinate muscle activity in four limbs. Spinal cord injury disrupts these interactions, impairing balance and interlimb coordination. We evoked reflexes by electrically stimulating left right superficial peroneal nerves before after two thoracic lateral hemisections placed on opposite sides of at 9‐ 13‐week interval seven adult cats (4 males 3 females). recorded reflex responses ten hindlimb five forelimb muscles bilaterally. After first (right T5–T6) second (left T10–T11) hemisections, coordination fore‐ hindlimbs was altered and/or became less consistent. hemisection, required assistance perform quadrupedal locomotion. Short‐latency homonymous crossed largely remained unaffected staggered hemisections. However, mid‐ long‐latency both occurred frequently In muscles, homolateral diagonal response occurrence significantly decreased all limbs, however, when present, short‐, maintained their phase‐dependent modulation. also observed reduced durations short‐latency inhibitory extensors early hemisection delayed ipsilesional hemisection. Therefore, changes correlated with impaired balance/stability locomotion spinal injury. Restoring transmission could be used as a biomarker facilitate locomotor recovery. image Key points Cutaneous afferent inputs limbs obstacle. Thoracic communication between centres located cervical lumbar levels, limb investigated nerve bilaterally, cats. showed loss/reduction which balance. Targeting pathways projecting help develop therapeutic approaches aimed restoring ascending descending pathways.

Language: Английский

---

Dual electrical stimulation at spinal-muscular interface reconstructs spinal sensorimotor circuits after spinal cord injury

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 19, 2024

Abstract The neural signals produced by varying electrical stimulation parameters lead to characteristic circuit responses. However, the characteristics of circuits reconstructed remain poorly understood, which greatly limits application such neuromodulation techniques for treatment spinal cord injury. Here, we develop a dual system that combines epidural and muscle mimic feedforward feedback in sensorimotor circuits. We demonstrate stimulus frequency 10−20 Hz under conditions is required structural functional reconstruction circuits, not only activates genes associated with axonal regeneration motoneurons, but also improves excitability neurons. Overall, results provide insights into signal decoding during reconstruction, suggesting combination promising method

Language: Английский

---

Phase-separated anisotropic PVA hydrogel loaded with tetramethylpyrazine for spinal cord injury repair

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 159944 - 159944

Published: Jan. 1, 2025

Language: Английский

---

Microneedle/CD-MOF-mediated transdural controlled release of methylprednisolone sodium succinate after spinal cord injury

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 360, P. 236 - 248

Published: June 27, 2023

Language: Английский

---

Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 9, 2023

Spinal cord injury (SCI) leads to severe sensory and motor dysfunction below the lesion. However, cellular dynamic responses heterogeneity across different regions lesion remain be elusive. Here, we used single-cell transcriptomics investigate region-related in female rhesus monkeys with complete thoracic SCI from acute chronic phases. We found that distal lumbar tissue cells were severely impacted, leading degenerative microenvironments characterized by disease-associated microglia oligodendrocytes activation alongside increased inhibitory interneurons proportion following SCI. By implanting scaffold into sites, could improve microenvironment through glial fibroblast regulation while remodeling spared tissues via reduced neurons improved phagocytosis myelination. Our findings offer crucial pathological insights proximal after SCI, emphasizing importance of scaffold-based treatment approaches targeting heterogeneous microenvironments.

Language: Английский

---

Embryonic exposure to environmental factors drives transmitter switching in the neonatal mouse cortex causing autistic-like adult behavior

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(35)

Published: Aug. 23, 2024

Autism spectrum disorders (ASD) can be caused by environmental factors. These factors act early in the development of nervous system and induce stereotyped repetitive behaviors diminished social interactions, among other outcomes. Little is known about how these are produced. In pregnant women, delivery valproic acid (VPA) (to control seizure activity or stabilize mood) immune activation a virus increases incidence ASD offspring. We found that either VPA Poly Inosine:Cytosine (which mimics viral infection), administered at mouse embryonic day 12.5, induced neurotransmitter switch from GABA to glutamate PV- CCK-expressing interneurons medial prefrontal cortex postnatal 10. The was present for only brief period during development, observed male female mice 21 reversed both males females 30. At 90, exhibited interaction while behavior. Transfecting GAD1 10, reintroduce expression, overrode prevented expression autistic-like findings point an important role switching mediating causes autism.

Language: Английский

---