Therapeutic effects of rapamycin and surgical decompression in a rabbit spinal cord injury model

Zhang, Xin; Qin, Chuan; Jing, Yingli; Yang, Degang; Liu, Changbin; Gao, Feng; Zhang, Chao; Talifu, Zuliyaer; Yang, Mingliang; Du, Liyong; Li, Jianjun

doi:10.1038/s41419-020-02767-5

Cited by 8 publications

(1 citation statement)

References 49 publications

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“…Rapamycin is currently in the clinic as a macrolide antibiotic, cancer treatment, immunosuppressive for transplantation, and cardiovascular treatment [ 145 ]. Preclinical studies demonstrate the neuroprotective effects of rapamycin following SCI [ 146 , 147 , 148 ]. These studies demonstrate that rapamycin reduces neuronal loss in the injured spinal cord [ 149 ].…”

Section: Pi3k-akt-mtor Networkmentioning

confidence: 99%

Translational Relevance of Secondary Intracellular Signaling Cascades Following Traumatic Spinal Cord Injury

Zavvarian,

Modi,

Sadat

et al. 2024

IJMS

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Traumatic spinal cord injury (SCI) is a life-threatening and life-altering condition that results in debilitating sensorimotor and autonomic impairments. Despite significant advances in the clinical management of traumatic SCI, many patients continue to suffer due to a lack of effective therapies. The initial mechanical injury to the spinal cord results in a series of secondary molecular processes and intracellular signaling cascades in immune, vascular, glial, and neuronal cell populations, which further damage the injured spinal cord. These intracellular cascades present promising translationally relevant targets for therapeutic intervention due to their high ubiquity and conservation across eukaryotic evolution. To date, many therapeutics have shown either direct or indirect involvement of these pathways in improving recovery after SCI. However, the complex, multifaceted, and heterogeneous nature of traumatic SCI requires better elucidation of the underlying secondary intracellular signaling cascades to minimize off-target effects and maximize effectiveness. Recent advances in transcriptional and molecular neuroscience provide a closer characterization of these pathways in the injured spinal cord. This narrative review article aims to survey the MAPK, PI3K-AKT-mTOR, Rho-ROCK, NF-κB, and JAK-STAT signaling cascades, in addition to providing a comprehensive overview of the involvement and therapeutic potential of these secondary intracellular pathways following traumatic SCI.

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Section: Pi3k-akt-mtor Networkmentioning

confidence: 99%

Translational Relevance of Secondary Intracellular Signaling Cascades Following Traumatic Spinal Cord Injury

Zavvarian,

Modi,

Sadat

et al. 2024

IJMS

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Reactive Oxygen Species‐Responsive Composite Fibers Regulate Oxidative Metabolism through Internal and External Factors to Promote the Recovery of Nerve Function

Zhu,

Zhou,

Tang

et al. 2024

Small

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It is challenging to sufficiently regulate endogenous neuronal reactive oxygen species (ROS) production, reduce neuronal apoptosis, and reconstruct neural networks under spinal cord injury conditions. Here, hydrogel surface grafting and microsol electrospinning are used to construct a composite biomimetic scaffold with “external‐endogenous” dual regulation of ROS. The outer hydrogel enhances local autophagy through responsive degradation and rapid release of rapamycin (≈80% within a week), neutralizing extracellular ROS and inhibiting endogenous ROS production, further reducing neuronal apoptosis. The inner directional fibers continuously supply brain‐derived neurotrophic factors to guide axonal growth. The results of in vitro co‐culturing show that the dual regulation of oxidative metabolism by the composite scaffold approximately doubles the neuronal autophagy level, reduces 60% of the apoptosis induced by oxidative stress, and increases the differentiation of neural stem cells into neuron‐like cells by ≈2.5 times. The in vivo results show that the composite fibers reduce the ROS levels by ≈80% and decrease the formation of scar tissue. RNA sequencing results show that composite scaffolds upregulate autophagy‐associated proteins, antioxidase genes, and axonal growth proteins. The developed composite biomimetic scaffold represents a therapeutic strategy to achieve neurofunctional recovery through programmed and accurate bidirectional regulation of the ROS cascade response.

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Neurochemical atlas of the rabbit spinal cord

Veshchitskii,

Shkorbatova,

Merkulyeva

2024

Brain Struct Funct

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Therapeutic effects of rapamycin and surgical decompression in a rabbit spinal cord injury model

Cited by 8 publications

References 49 publications

Translational Relevance of Secondary Intracellular Signaling Cascades Following Traumatic Spinal Cord Injury

Translational Relevance of Secondary Intracellular Signaling Cascades Following Traumatic Spinal Cord Injury

Reactive Oxygen Species‐Responsive Composite Fibers Regulate Oxidative Metabolism through Internal and External Factors to Promote the Recovery of Nerve Function

Neurochemical atlas of the rabbit spinal cord

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