Photobiomodulation by diffusing optical fiber on spinal cord: A feasibility study in piglet model

Liang, Zhicheng; Tao, Ling; Wang, Shuang; Zuo, Xiaoshuang; Li, Kun; Song, Jiwei; Sun, Jiakai; Zhang, Jiawei; Zhou, Qiao; Kang, Xiaofeng; Ma, Yinbo; Hu, Xueyu; Ding, Tan; Wang, Zhe

doi:10.1002/jbio.201960022

Cited by 22 publications

(20 citation statements)

References 30 publications

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“…In this study, we improved the application of PBM by embedding laser fibers into rats subjected to SCI instead of using indirect transcutaneous irradiation to better project the laser to the damaged tissue; the feasibility and safety of this strategy were verified previously (Liang et al, 2019;Zuo et al, 2021). We discovered that PBM induced the transformation of neurotoxic (A1) astrocytes to neuroprotective (A2) astrocytes, which may be a promising strategy for treating SCI, as demonstrated in recent reports (Liu et al, 2019;Qian et al, 2019;Su et al, 2019;Vismara et al, 2020;Zou et al, 2021).…”

Section: Discussionmentioning

confidence: 69%

Photobiomodulation Promotes Repair Following Spinal Cord Injury by Regulating the Transformation of A1/A2 Reactive Astrocytes

et al. 2021

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After spinal cord injury (SCI), reactive astrocytes can be classified into two distinctive phenotypes according to their different functions: neurotoxic (A1) astrocytes and neuroprotective (A2) astrocytes. Our previous studies proved that photobiomodulation (PBM) can promote motor function recovery and improve tissue repair after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM contributes to repair after SCI by regulating the activation of astrocytes. Male rats subjected to clip-compression SCI were treated with PBM for two consecutive weeks, and the results showed that recovery of motor function was improved, the lesion cavity size was reduced, and the number of neurons retained was increased. We determined the time course of A1/A2 astrocyte activation after SCI by RNA sequencing (RNA-Seq) and verified that PBM inhibited A1 astrocyte activation and promoted A2 astrocyte activation at 7 days postinjury (dpi) and 14 dpi. Subsequently, potential signaling pathways related to A1/A2 astrocyte activation were identified by GO function analysis and KEGG pathway analysis and then studied in animal experiments and preliminarily analyzed in cultured astrocytes. Next, we observed that the expression of basic fibroblast growth factor (bFGF) and transforming growth factor-β (TGF-β) was upregulated by PBM and that both factors contributed to the transformation of A1/A2 astrocytes in a dose-dependent manner. Finally, we found that PBM reduced the neurotoxicity of A1 astrocytes to dorsal root ganglion (DRG) neurons. In conclusion, PBM can promote better recovery after SCI, which may be related to the transformation of A1/A2 reactive astrocytes.

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Section: Discussionmentioning

confidence: 69%

Photobiomodulation Promotes Repair Following Spinal Cord Injury by Regulating the Transformation of A1/A2 Reactive Astrocytes

et al. 2021

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“…Due to the complexity of the pathophysiological process of SCI and the timing of the intervention window, many current treatments have unclear mechanisms and large side effects that limit their clinical applications [46,47]. In this study, we tried to verify an optimized PBM treatment by embedding biocompatible laser bres next to the vertebral body in the process of modelling SCI based on previous studies [30,48] to better project laser energy to the surface of the injured spinal cord. Continuous irradiation every day after SCI and PBM can effectively play a therapeutic role in both the acute and subacute phases, leading to better motor function recovery outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…The parameters of the laser irradiation were set according to previous research [28,30]. Rats were slightly anaesthetized and put into a warm cage, and a continuous 810 nm diode laser (MW-GX-808, Lei Shi Optoelectronics Co., Ltd. Changchun, China, 810 nm wavelength, 150 mW output power) was used in the embedded laser bre focused on the SCI site.…”

Section: Laser Irradiationmentioning

confidence: 99%

Photobiomodulation Inhibits the Activation of Neurotoxic Microglia and Astrocytes Through Inhibiting the Crosstalk of Lcn2/JAK2-STAT3 after Spinal Cord Injury in Rats

Wang

Zuo

et al. 2021

Preprint

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BackgroundIn situ microglia and astrocytes begin to activate and participate in neuroinflammation after spinal cord injury (SCI), and the high expression of lipocalin 2 (Lcn2) and the activation of the Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) pathway promote the polarization of activated microglia and astrocytes towards the neurotoxic phenotype (M1 microglia and A1 astrocytes). We previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but the mechanism of PBM on the microglia and astrocytes involved is still unclear. Therefore, the purpose of this study was to explore the role of the Lcn2 and JAK2-STAT3 pathways in the activation of M1 and A1 and the mechanism by which PBM may play a therapeutic role.MethodsPBM intervention was performed every day after the SCI model was established, and the activation of microglia and astrocytes was observed at different time points post injury (1, 3, 7, 14, 28 dpi). The level of tissue apoptosis, the number of surviving neurons, the recovery of motor function, the level of Lcn2 and the activation of JAK2-STAT3 were evaluated in the PBM group and the vehicle group. M1 and A1 cells were irradiated with PBM in vitro, and the JAK2-STAT3 pathway inhibitor cucurbitacin I, adenovirus transfection and recombinant Lcn2 protein were cotreated with PBM to explore the mechanism of the activation of M1 and A1 and the underlying effect of PBM.ResultsPBM inhibited the activation of neurotoxic microglia and astrocytes, decreased secondary inflammation and tissue apoptosis, increased the number of neurons retained, and promoted the recovery of motor function after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also proved that PBM can inhibit the activation of M1 microglia and A1 astrocytes, and the effect is related to the level of Lcn2 and the activation of the JAK2-STAT3 pathway.ConclusionThe crosstalk of Lcn2/JAK2-STAT3 is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be alleviated by PBM.

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“…Moreover, pigs are friendly, easier to handle than primates, and their size is well-suited for testing surgical setups and devices designed for humans. Therefore, they have been promising candidates for testing different neuromodulation strategies such as intraspinal microstimulation [7], [18], epidural stimulation, [19] and photobiomodulation [20]. This is done using devices and surgical technologies identical to those performed intraoperatively, or intended to be performed, in humans [20], [21].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, they have been promising candidates for testing different neuromodulation strategies such as intraspinal microstimulation [7], [18], epidural stimulation, [19] and photobiomodulation [20]. This is done using devices and surgical technologies identical to those performed intraoperatively, or intended to be performed, in humans [20], [21]. Domestic pigs gain weight non-linearly during their first two years of life and can reach more than 300 kg.…”

Section: Introductionmentioning

confidence: 99%

Overground Gait Kinematics and Muscle Activation Patterns in the Yucatan Mini Pig

Mirkiani

et al. 2021

Preprint

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A growing number of spinal cord injury, neuromodulation, and cell therapy studies on porcine models, especially the Yucatan minipigs (YMPs), have been recently reported. This is due to the large similarities between human and porcine neuroanatomy and biomechanics. To assess treatment modalities and locomotor recovery in this model, there is an obvious need for detailed characterization of normative overground gait in neurologically intact YMPs. The objective of this study was to assess gait biomechanics and the effect of overground walking speed on gait parameters, kinematics, and electromyographic (EMG) activity in the hindlimb muscles of YMPs. Nine neurologically-intact adult YMPs were trained to walk overground in a straight line. Whole-body kinematics and EMG activity of hindlimb muscles were recorded and analyzed at 6 different speed ranges (0.4-0.59, 0.6-0.79, 0.8-0.99, 1.0-1.19, 1.2-1.39, and 1.4-1.6 m/s). A MATLAB program was developed to detect strides and gait events automatically from motion-captured data. Significant decreases in stride duration, stance and swing times and an increase in stride length were observed with increasing speed. A transition in gait pattern occurred at the 1.0m/s walking speed. Significant increases in the range of motion of the knee and ankle joints were observed at higher speeds. Also, the points of minimum and maximum knee and ankle joint angles occurred earlier in the gait cycle at higher speeds. The onset of EMG activity in the biceps femoris muscle occurred significantly earlier in the gait cycle with increasing speed. A comprehensive characterization of overground walking in neurologically-intact YMPs is provided. These normative measures set the basis against which the effects of future interventions on locomotor capacity in YMPs can be compared.

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Photobiomodulation by diffusing optical fiber on spinal cord: A feasibility study in piglet model

Abstract: Previous studies on spinal cord injury (SCI) have confirmed that percutaneous photobiomodulation (PBM) therapy can ameliorate immunoinflammatory responses at

Cited by 22 publications

References 30 publications

Photobiomodulation Promotes Repair Following Spinal Cord Injury by Regulating the Transformation of A1/A2 Reactive Astrocytes

Photobiomodulation Promotes Repair Following Spinal Cord Injury by Regulating the Transformation of A1/A2 Reactive Astrocytes

Photobiomodulation Inhibits the Activation of Neurotoxic Microglia and Astrocytes Through Inhibiting the Crosstalk of Lcn2/JAK2-STAT3 after Spinal Cord Injury in Rats

Overground Gait Kinematics and Muscle Activation Patterns in the Yucatan Mini Pig

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