Activity of spinal RORβ neurons is related to functional improvements following combination treatment after complete SCI DOI Creative Commons
Nicholas J. Stachowski,

Jaimena H. Wheel,

Shayna Singh

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(15)

Published: April 8, 2025

Various strategies targeting spinal locomotor circuitry have been associated with functional improvements after cord injury (SCI). However, the neuronal populations mediating beneficial effects remain largely unknown. Using a combination therapy in mouse model of complete SCI, we show that virally delivered brain-derived neurotrophic factor (BDNF) (AAV-BDNF) activates hindlimb stepping and causes hyperreflexia, whereas submotor threshold epidural stimulation (ES) reduces BDNF-induced hyperreflexia. Given their role gating proprioceptive afferents as potential convergence point BDNF ES, hypothesized an enhanced excitability inhibitory RORβ neurons would be improvements. Ex vivo slice recordings from mice range hyperreflexia scores revealed was related to outcome post-SCI. Mice poor function SCI had less excitable neurons, but similar between uninjured “best stepping” groups. Further, chemogenetic activation reduced improved stepping, ES. Our findings identify target population limit enhance SCI.

Language: Английский

Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair DOI Creative Commons
Vishnu Muraleedharan Saraswathy, Zhou Li-li, Mayssa H. Mokalled

et al.

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

Published: Aug. 15, 2024

Adult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during repair. Neurogenesis glutamatergic GABAergic neurons restores the excitatory/inhibitory balance after In addition, transient population injury-responsive (iNeurons) show elevated 1 week post-injury. found iNeurons are injury-surviving acquire neuroblast-like gene expression signature CRISPR/Cas9 mutagenesis showed required functional recovery employ vesicular trafficking as essential mechanism underlies plasticity. This study provides resource cells mechanisms direct regeneration establishes model plasticity-driven neural

Language: Английский

Citations

6
Chaperone-Mediated Autophagy in Brain Injury: A Double-Edged Sword with Therapeutic Potentials DOI
Huiyi Zhang, Ye Tian, Shuai Ma

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(12), P. 10671 - 10683

Published: May 22, 2024

Language: Английский

Citations

5
Tail nerve electrical stimulation promoted the efficiency of transplanted spinal cord-like tissue as a neuronal relay to repair the motor function of rats with transected spinal cord injury DOI
Bi‐Qin Lai, Rongjie Wu, Weitao Han

et al.

Biomaterials, Journal Year: 2023, Volume and Issue: 297, P. 122103 - 122103

Published: March 28, 2023

Language: Английский

Citations

13
Neuroplasticity and regeneration after spinal cord injury DOI Creative Commons

Nayaab Punjani,

Dylan Deska‐Gauthier, Laureen D. Hachem

et al.

North American Spine Society Journal (NASSJ), Journal Year: 2023, Volume and Issue: 15, P. 100235 - 100235

Published: June 8, 2023

Spinal cord injury (SCI) is a debilitating condition with significant personal, societal, and economic burden. The highest proportion of traumatic injuries occur at the cervical level, which results in severe sensorimotor autonomic deficits. Following initial physical trauma associated injuries, secondary pro-inflammatory, excitotoxic, ischemic cascades are initiated further contributing to neuronal glial cell death. Additionally, emerging evidence has begun reveal that spinal interneurons undergo subtype specific neuroplastic circuit rearrangements weeks months following SCI, or hindering functional recovery. current therapeutic guidelines standards care for SCI patients include early surgery, hemodynamic regulation, rehabilitation. preclinical work ongoing clinical trials have exploring neuroregenerative strategies utilizing endogenous neural stem/progenitor cells, stem transplantation, combinatorial approaches, direct reprogramming. This review will focus on cellular non-cellular regenerative therapies an overview available strategies, role plasticity, exciting research avenues enhancing tissue repair SCI.

Language: Английский

Citations

13
Distinguishing subtypes of spinal locomotor neurons to inform circuit function and dysfunction DOI
Kimberly J. Dougherty

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 82, P. 102763 - 102763

Published: Aug. 21, 2023

Language: Английский

Citations

11
Neuronal repair after spinal cord injury by in vivo astrocyte reprogramming mediated by the overexpression of NeuroD1 and Neurogenin-2 DOI Creative Commons

Zuliyaer Talifu,

Chunjia Zhang,

Xin Xu

et al.

Biological Research, Journal Year: 2024, Volume and Issue: 57(1)

Published: Aug. 12, 2024

Abstract Background As a common disabling disease, irreversible neuronal death due to spinal cord injury (SCI) is the root cause of functional impairment; however, capacity for regeneration in developing tissue limited. Therefore, there an urgent need investigate how defective neurons can be replenished and functionally integrated by neural regeneration; reprogramming intrinsic cells into may represent ideal solution. Methods A mouse model transection SCI was prepared forceps clamping, adeno-associated virus (AAV) carrying transcription factors NeuroD1 Neurogenin-2(Ngn2) injected situ specifically overexpress these astrocytes close site. 5-bromo-2´-deoxyuridine (BrdU) subsequently intraperitoneally continuously track cell regeneration, neuroblasts immature marker expression, glial scar regeneration. In addition, immunoprotein blotting used measure levels transforming growth factor-β (TGF-β) pathway-related protein expression. We also evaluated motor function, sensory integrity blood-spinal barrier(BSCB). Results The overexpression Ngn2 achieved specific AAV vectors. This intervention led significant increase proportion with properties at site(p < 0.0001). Immunofluorescence staining identified site while marker-specific revealed increased number mature Behavioral assessments showed that did not improve BMS (Basso scale) score (p = 0.0726) gait > 0.05), although treated mice had more sensitivity greater voluntary ability open field than non-intervention mice. observed repair BSCB center 0.0001) improvement proliferation. Electrophysiological nerve conduction immunostaining TGF-β group were lower control 0.0034); P70 s6 PP2A related pathway ascending trend 0.0036, p 0.0152 respectively). Conclusions after reprogram significantly enhance lead repair, thus improving reduced threshold increasing movements. strategy barrier function. However, simple cannot improvements striding function limbs.

Language: Английский

Citations

4
Natural polymer based drug-loaded hydrogel platform for comprehensive care of acute spinal cord injury DOI Creative Commons
Mingyu Zhang,

Chunyu Xiang,

Xin Zhen

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101464 - 101464

Published: Jan. 7, 2025

Traumatic spinal cord injury typically occurs at significant depths and triggers rapid severe physiological responses. It is commonly accompanied by oxidative stress disorders, lipid peroxidation, accumulation of toxic aldehydes, edema among other symptoms. The management this condition requires intricate surgical procedures vigilance against postoperative complications. Slow wound healing a major clinical challenge. In study, we developed an injectable hydrogel-based smart drug delivery platform (OPDL gel) for the treatment injuries integrated care. hydrogel encapsulates glucocorticoid dexamethasone (Dex) through borate ester bond can respond to degradation caused reactive oxygen species (ROS) pH changes in microenvironment injuries. OPDL gel was injected into lesion with period 60 h, enabling controlled intelligent release Dex. Additionally, poly-ε-lysine macromolecules within absorb aldehydes present via Schiff base reactions, thereby mitigating secondary progression injury. When locally applied injuries, demonstrated good biocompatibility had protective effect on damaged neural structures. addition, also exhibited excellent bactericidal properties, achieving 100 % kill rate microorganisms 80 min providing care comparable commercial product, Tegaderm™. Therefore, multifunctional drug-loading represents novel approach strategies setting address

Language: Английский

Citations

0
How the brain produces generalized fear DOI Creative Commons

Hui-quan Li,

Nicholas C. Spitzer

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Language: Английский

Citations

0
Engineered hybrid exosomes responsive to reactive oxygen species target the treatment of spinal cord injury by repairing mitochondrial damage and promoting neuronal function recovery DOI

Daoyong Li,

Zhanpeng Guo,

Mingyu Bai

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 160669 - 160669

Published: Feb. 1, 2025

Language: Английский

Citations

0
Harnessing spinal circuit reorganization for targeted functional recovery after spinal cord injury DOI Creative Commons
Xin Sun, Lijuan Li, Liyi Huang

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106854 - 106854

Published: Feb. 1, 2025

Spinal cord injury (SCI) disrupts the communication between brain and spinal cord, resulting in loss of motor function below site. However, spontaneous structural functional plasticity occurs neural circuits after SCI, with unaffected synaptic inputs forming new connections detour pathways to support recovery. The review discusses various mechanisms circuit reorganization post-SCI, including supraspinal pathways, interneurons, central pattern generators. Functional recovery may rely on maintaining a balance excitatory inhibitory activity, as well enhancing proprioceptive input, which plays key role limb stability. emphasizes importance endogenous neuronal regeneration, neuromodulation therapies (such electrical stimulation) proprioception SCI treatment. Future research should integrate advanced technologies such gene targeting, imaging, single-cell mapping better understand underpinning recovery, aiming identify subpopulations for targeted reconstruction enhanced By harnessing reorganization, these efforts hold potential pave way more precise effective strategies SCI.

Language: Английский

Citations

0