Photobiomodulation and diffusing optical fiber on spinal cord’s impact on nerve cells from normal spinal cord tissue in piglets

Zuo, Xiaoshuang; Liang, Zhicheng; Zhang, Jiawei; Wang, Shuang; Zhou, Qiao; Ma, Yinbo; Li, Penghui; Ding, Tan; Hu, Xueyu; Wang, Zhe

doi:10.1007/s10103-020-03231-8

Cited by 9 publications

(6 citation statements)

References 33 publications

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“…In this study, we used an implantable biofibre to deliver 808-nm NIR light directly to the surface of the injured spinal cord ( 25 , 26 ). This PBM treatment model inhibited neurotoxic polarization of macrophages and secretion of inflammatory factors in the SCI area of mice, leading to a significant enhancement of motor function.…”

Section: Discussionmentioning

confidence: 99%

“…A continuous 808-nm semiconductor laser (MW-GX-808, Lei Shi Optoelectronics Co., Ltd. Changchun, China) and its matched medical diffusing optical fibre were used for PBM therapy in mice. The safety of the optical fibre and the irradiation parameters has been validated in piglet models ( 25 , 26 ). The highly transparent medical silica coating on the fibre surface ensures flexibility and biocompatibility without affecting its optical properties.…”

Section: Methodsmentioning

confidence: 99%

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Photobiomodulation Attenuates Neurotoxic Polarization of Macrophages by Inhibiting the Notch1-HIF-1α/NF-κB Signalling Pathway in Mice With Spinal Cord Injury

Cheng

et al. 2022

Front. Immunol.

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Spinal cord injury (SCI) is a catastrophic disease with a complex pathogenesis that includes inflammation, oxidative stress, and glial scar formation. Macrophages are the main mediators of the inflammatory response and are distributed in the epicentre of the SCI. Macrophages have neurotoxic and neuroprotective phenotypes (also known as classically and alternatively activated macrophages or M1 and M2 macrophages) that are associated with pro- or anti- inflammatory gene expression. Our previous study demonstrated that photobiomodulation (PBM) alters the polarization state of macrophages in the SCI region towards the M2 phenotype and promotes the recovery of motor function in rats with SCI. However, the mechanism by which PBM promotes SCI repair remains largely undefined. This study is based on the replacement of conventional percutaneous irradiation with implantable biofibre optic in vivo irradiation. The aim was to further investigate the effects of PBM on SCI in mice under new irradiation patterns and its potential mechanisms of action. PBM was administered to male mice with clamped SCI for four consecutive weeks and significantly promoted the recovery of motor function in mice. Analysis of the macrophage phenotypes in the epicentre of the SCI in mice showed that PBM mainly inhibited the neurotoxic activation of macrophages in the SCI area and reduced the secretion of inflammatory factors such as IL-1α and IL-6; PBM had no effect on M2 macrophages. Immediately afterwards, we constructed in vitro models of the inflammatory polarization of macrophages and PBM intervention. We found that PBM attenuated the neurotoxicity of M1 macrophages on VSC 4.1 motor neurons and dorsal root ganglion (DRG) neurons. The effects of PBM on neurotoxic macrophages and the possible mechanisms of action were analysed using RNA sequencing (RNA-seq), which confirmed that the main role of PBM was to modulate the inflammatory response and immune system processes. Analysis of the differentially expressed genes (DEGs) associated with the inflammatory response showed that PBM had the most significant regulatory effects on genes such as interleukin (IL)-1α, IL-6, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and had obvious inhibitory effects on inflammation-related Notch1 and hypoxia-inducible factor-1α (HIF-1α) pathway genes. RNA-seq analysis of the effect of PBM on gene expression in resting-state macrophages and M2 macrophages did not show significant differences (data not shown). In conclusion, PBM promoted better motor recovery after SCI in mice by inhibiting the neurotoxic polarization of macrophages and the release of inflammatory mediators by acting on the Notch1-HIF-1α/NF-κB Signalling Pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Photobiomodulation Attenuates Neurotoxic Polarization of Macrophages by Inhibiting the Notch1-HIF-1α/NF-κB Signalling Pathway in Mice With Spinal Cord Injury

Cheng

et al. 2022

Front. Immunol.

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“…Importantly, we anticipate that this approach has complementary applications from BBB opening using ultrasound and microbubbles. For example, it is challenging to apply ultrasound to tissues behind complicated bone structures such as the spinal cord, while it is straightforward to apply laser fiber optics in the spinal cord with minimal invasiveness. , Other targets of interest include the tumor margin around the surgical cavity of a brain tumor, since it is surgically accessible by light . Future work includes delivery of a therapeutic antibody, viral and nonviral vectors for disease treatment in these targets, investigation of the precise mechanism, and long-term brain health.…”

Section: Discussionmentioning

confidence: 99%

Reversibly Modulating the Blood–Brain Barrier by Laser Stimulation of Molecular-Targeted Nanoparticles

Vemireddy

Cai

et al. 2021

Nano Lett.

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The blood−brain barrier (BBB) is highly selective and acts as the interface between the central nervous system and circulation. While the BBB is critical for maintaining brain homeostasis, it represents a formidable challenge for drug delivery.Here we synthesized gold nanoparticles (AuNPs) for targeting the tight junction specifically and demonstrated that transcranial picosecond laser stimulation of these AuNPs post intravenous injection increases the BBB permeability. The BBB permeability change can be graded by laser intensity, is entirely reversible, and involves increased paracellular diffusion. BBB modulation does not lead to significant disruption in the spontaneous vasomotion or the structure of the neurovascular unit. This strategy allows the entry of immunoglobulins and viral gene therapy vectors, as well as cargoladen liposomes. We anticipate this nanotechnology to be useful for tissue regions that are accessible to light or fiberoptic application and to open new avenues for drug screening and therapeutic interventions in the central nervous system.

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“…Therefore, we have developed biocompatible laser fibers that can be implanted beside the lamina in vivo to project laser energy directly onto the spinal cord surface with appropriate irradiation parameters. This strategy reduces energy scattering and passive absorption by body tissues, thus exerting a better biotherapeutic effect, and the feasibility and safety of this strategy has been reliably verified [ 30 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats

Wang

Zuo

et al. 2021

J Neuroinflammation

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Background Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM ameliorates neuroinflammation by modulating the activation of microglia and astrocytes after SCI. Methods Male Sprague–Dawley rats were randomly divided into three groups: a sham control group, an SCI + vehicle group and an SCI + PBM group. PBM was performed for two consecutive weeks after clip-compression SCI models were established. The activation of neurotoxic microglia and astrocytes, the level of tissue apoptosis, the number of motor neurons and the recovery of motor function were evaluated at different days post-injury (1, 3, 7, 14, and 28 days post-injury, dpi). Lipocalin 2 (Lcn2) and Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) signaling were regarded as potential targets by which PBM affected neurotoxic microglia and astrocytes. In in vitro experiments, primary microglia and astrocytes were irradiated with PBM and cotreated with cucurbitacin I (a JAK2-STAT3 pathway inhibitor), an adenovirus (shRNA-Lcn2) and recombinant Lcn2 protein. Results PBM promoted the recovery of motor function, inhibited the activation of neurotoxic microglia and astrocytes, alleviated neuroinflammation and tissue apoptosis, and increased the number of neurons retained after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also showed that Lcn2 and JAK2-STAT3 were mutually promoted and that PBM interfered with this interaction, inhibiting the activation of microglia and astrocytes. Conclusion Lcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM.

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Photobiomodulation and diffusing optical fiber on spinal cord’s impact on nerve cells from normal spinal cord tissue in piglets

Cited by 9 publications

References 33 publications

Photobiomodulation Attenuates Neurotoxic Polarization of Macrophages by Inhibiting the Notch1-HIF-1α/NF-κB Signalling Pathway in Mice With Spinal Cord Injury

Photobiomodulation Attenuates Neurotoxic Polarization of Macrophages by Inhibiting the Notch1-HIF-1α/NF-κB Signalling Pathway in Mice With Spinal Cord Injury

Reversibly Modulating the Blood–Brain Barrier by Laser Stimulation of Molecular-Targeted Nanoparticles

Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats

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