Deciphering glial scar after spinal cord injury

Zhang, Yu; Yang, Shuhai; Liu, Chang; Han, Xiaoxiao; Gu, Xiaosong; Zhou, Songlin

doi:10.1093/burnst/tkab035

Cited by 25 publications

(17 citation statements)

References 99 publications

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“…Around 14 days after SCI, activated microglia and proliferating fibroblasts occupy the lesion core of the glial scar [ 27 ]. And the M1 type microglia is dominant and persist, which may induce axon damage [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Bu Shen Huo Xue decoction promotes functional recovery in spinal cord injury mice by improving the microenvironment to promote axonal regeneration

et al. 2022

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Background Bu-Shen-Huo-Xue (BSHX) decoction has been used in the postoperative rehabilitation of patients with spinal cord injury in China. In the present study, we aim to reveal the bioactive compounds in BSHX decoction and comprehensively explore the effects of BSHX decoction and the underlying mechanism in spinal cord injury recovery. Methods The main chemical constituents in BSHX decoction were determined by UPLC–MS/MS. SCI mice were induced by a pneumatic impact device at T9–T10 level of the vertebra, and treated with BSHX decoction. Basso–Beattie–Bresnahan (BBB) score, footprint analysis, hematoxylin–eosin (H&E) staining, Nissl staining and a series of immunofluorescence staining were performed to investigate the functional recovery, glial scar formation and axon regeneration after BSHX treatment. Immunofluorescent staining of bromodeoxyuridine (BrdU), neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) was performed to evaluate the effect of BSHX decoction on neural stem cells (NSCs) proliferation and differentiation. Results We found that the main compounds in BSHX decoction were Gallic acid, 3,4-Dihydroxybenzaldehyde, (+)-Catechin, Paeoniflorin, Rosmarinic acid, and Diosmetin. BSHX decoction improved the pathological findings in SCI mice through invigorating blood circulation and cleaning blood stasis in the lesion site. In addition, it reduced tissue damage and neuron loss by inhibiting astrocytes activation, and promoting the polarization of microglia towards M2 phenotype. The functional recovery test revealed that BSHX treatment improved the motor function recovery post SCI. Conclusions Our study provided evidence that BSHX treatment could improve the microenvironment of the injured spinal cord to promote axonal regeneration and functional recovery in SCI mice.

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Section: Resultsmentioning

confidence: 99%

Bu Shen Huo Xue decoction promotes functional recovery in spinal cord injury mice by improving the microenvironment to promote axonal regeneration

et al. 2022

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“…21 The microglia enhancement of glial scars is hypothesized to be related to a failed switch from M1 back to M2 type. 22 Resolving scar tissue barriers requires understanding the intricate mixture of cell types that include astrocytic, fibrotic, and microglial cells.…”

Section: The Sci Microenvironment and Roles Of Astrocytes Inflammatio...mentioning

confidence: 99%

Human stem cell–derived neurons and neural circuitry therapeutics: Next frontier in spinal cord injury repair

Paredes-Espinosa

Paluh

2022

Exp Biol Med (Maywood)

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Spinal cord injury (SCI) remains a life-altering event that devastates those injured and the families that support them. Numerous laboratories are engaged in preclinical and clinical trials to repair the injured spinal cord with stem cell–derived therapeutics. A new developmental paradigm reveals early bifurcation of brain or trunk neurons in mammals via neuromesodermal progenitors (NMPs) relevant to therapies requiring homotypic spinal cord neural populations. Human-induced pluripotent stem cell (hiPSC) NMP-derived spinal motor neurons generated ex vivo following this natural developmental route demonstrate robust survival in vivo when delivered as suspension grafts or as in vitro preformed encapsulated neuronal circuitry when transplanted into a rat C4-C5 hemicontusion injury site. Use of in vitro matured neurons avoids in vivo differentiation challenges of using pluripotent hiPSC or multipotent neural stem cell (NSC) or mesenchymal stem cell therapeutics. In this review, we provide an injury to therapeutics overview focusing on how stem cell and developmental fields are merging to generate exquisitely matched spinal motor neurons for SCI therapeutic studies. The complexity of the SCI microenvironment generated by trauma to neurons and vasculature, along with infiltrating inflammatory cells and scarring, underlies the challenging cytokine microenvironment that therapeutic cells encounter. An overview of evolving but limited stem cell–based SCI therapies that have progressed from preclinical to clinical trials illustrates the challenges and need for additional stem cell–based therapeutic approaches. The focus here on neurons describes how NMP-based neurotechnologies are advancing parallel strategies such as transplantation of preformed neuronal circuitry as well as human in vitro gastruloid multicellular models of trunk central and peripheral nervous system integration with organs. NMP-derived neurons are expected to be powerful drivers of the next generation of SCI therapeutics and integrate well with combination therapies that may utilize alternate biomimetic scaffolds for bridging injuries or flexible biodegradable electronics for electrostimulation.

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“…Peripheral nerve injury is a serious disease in clinical medicine, which has diverse pathogenic factors, including trauma, surgical accidents, sports injuries, etc. [ 1 , 2 ]. Although most peripheral nerve injuries do not endanger human life, partial nerve defects hinder functions of normal surrounding tissue and cause action inconvenience and paresthesia to patients, which adversely affects people’s daily life [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Co-culture of Schwann cells and endothelial cells for synergistically regulating dorsal root ganglion behavior on chitosan-based anisotropic topology for peripheral nerve regeneration

Zheng

Sun

et al. 2022

Burns &Amp; Trauma

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Background Anisotropic topologies are known to regulate cell-oriented growth and induce cell differentiation, which is conducive to accelerating nerve regeneration, while co-culture of endothelial cells (ECs) and Schwann cells (SCs) can significantly promote the axon growth of dorsal root ganglion (DRG). However, the synergistic regulation of EC and SC co-culture of DRG behavior on anisotropic topologies is still rarely reported. The study aims to investigate the effect of anisotropic topology co-cultured with Schwann cells and endothelial cells on dorsal root ganglion behavior for promoting peripheral nerve regeneration. Methods Chitosan/artemisia sphaerocephala (CS/AS) scaffolds with anisotropic topology were first prepared using micro-molding technology, and then the surface was modified with dopamine to facilitate cell adhesion and growth. The physical and chemical properties of the scaffolds were characterized through morphology, wettability, surface roughness and component variation. SCs and ECs were co-cultured with DRG cells on anisotropic topology scaffolds to evaluate the axon growth behavior. Results Dopamine-modified topological CS/AS scaffolds had good hydrophilicity and provided an appropriate environment for cell growth. Cellular immunofluorescence showed that in contrast to DRG growth alone, co-culture of SCs and ECs could not only promote the growth of DRG axons, but also offered a stronger guidance for orientation growth of neurons, which could effectively prevent axons from tangling and knotting, and thus may significantly inhibit neurofibroma formation. Moreover, the co-culture of SCs and ECs could promote the release of nerve growth factor and vascular endothelial growth factor, and up-regulate genes relevant to cell proliferation, myelination and skeletal development via the PI3K-Akt, MAPK and cytokine and receptor chemokine pathways. Conclusions The co-culture of SCs and ECs significantly improved the growth behavior of DRG on anisotropic topological scaffolds, which may provide an important basis for the development of nerve grafts in peripheral nerve regeneration.

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Deciphering glial scar after spinal cord injury

Cited by 25 publications

References 99 publications

Bu Shen Huo Xue decoction promotes functional recovery in spinal cord injury mice by improving the microenvironment to promote axonal regeneration

Bu Shen Huo Xue decoction promotes functional recovery in spinal cord injury mice by improving the microenvironment to promote axonal regeneration

Human stem cell–derived neurons and neural circuitry therapeutics: Next frontier in spinal cord injury repair

Co-culture of Schwann cells and endothelial cells for synergistically regulating dorsal root ganglion behavior on chitosan-based anisotropic topology for peripheral nerve regeneration

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