Implantable and transcutaneous photobiomodulation promote neuroregeneration and recovery of lost function after spinal cord injury

IF 6.1 2区医学 Q1 ENGINEERING, BIOMEDICAL

Bioengineering & Translational Medicine Pub Date : 2024-04-26 DOI:10.1002/btm2.10674

Andrew R. Stevens, Mohammed Hadis, Alice Phillips, Abhinav Thareja, Michael Milward, Antonio Belli, William Palin, David J. Davies, Zubair Ahmed

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引用次数: 0

Abstract

Spinal cord injury (SCI) is a cause of profound and irreversible damage, with no effective therapy to promote functional recovery. Photobiomodulation (PBM) may provide a viable therapeutic approach using red or near‐infrared light to promote recovery after SCI by mitigating neuroinflammation and preventing neuronal apoptosis. Our current study aimed to optimize PBM dose regimens and develop and validate the efficacy of an invasive PBM delivery paradigm for SCI. Dose optimization studies were performed using a serum withdrawal model of injury in cultures of primary adult rat dorsal root ganglion neurons (DRGN). Implantable and transcutaneous PBM delivery protocols were developed and validated using cadaveric modeling. The efficacy of PBM in promoting recovery after SCI in vivo was studied in a dorsal column crush injury model of SCI in adult rats. Optimal neuroprotection in vitro was achieved between 4 and 22 mW/cm2. 11 mW/cm2 for 1 min per day (0.66 J/cm2) increased cell viability by 45% over 5 days (p <0.0001), increasing neurite outgrowth by 25% (p <0.01). A method for invasive application of PBM was developed using a diffusion‐tipped optogenetics fiber optic. Delivery methods for PBM were developed and validated for both invasive (iPBM) and noninvasive (transcutaneous) (tcPBM) application. iPBM and tcPBM (24 mW/cm2 at spinal cord, 1 min per day (1.44 J/cm2) up to 7 days) increased activation of regeneration‐associated protein at 3 days after SCI, increasing GAP43+ axons in DRGN from 18.0% (control) to 41.4% ± 10.5 (iPBM) and 45.8% ± 3.4 (tcPBM) (p <0.05). This corresponded to significant improvements at 6 weeks post‐injury in functional locomotor and sensory function recovery (p <0.01), axonal regeneration (p <0.01), and reduced lesion size (p <0.01). Our results demonstrated that PBM achieved a significant therapeutic benefit after SCI, either using iPBM or tcPBM application and can potentially be developed for clinical use in SCI patients.

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植入式和经皮光生物调制促进脊髓损伤后的神经再生和丧失功能的恢复

脊髓损伤（SCI）是造成严重和不可逆损伤的原因之一，目前还没有有效的疗法来促进功能恢复。光生物调控（PBM）可提供一种可行的治疗方法，利用红光或近红外光减轻神经炎症并防止神经元凋亡，从而促进脊髓损伤后的恢复。我们目前的研究旨在优化 PBM 剂量方案，并开发和验证用于 SCI 的侵入性 PBM 给药范例的疗效。我们在原代成年大鼠背根神经节神经元（DRGN）培养物中使用血清抽取损伤模型进行了剂量优化研究。利用尸体模型开发并验证了植入式和经皮 PBM 给药方案。在成年大鼠背柱挤压伤模型中研究了 PBM 促进体内 SCI 后恢复的功效。体外神经保护的最佳值为 4 至 22 mW/cm2。每天 1 分钟 11 mW/cm2（0.66 J/cm2）可使细胞存活率在 5 天内提高 45%（p <0.0001），使神经元生长速度提高 25%（p <0.01）。利用扩散尖端光遗传学光纤开发了一种侵入性应用 PBM 的方法。开发并验证了有创（iPBM）和无创（经皮）（tcPBM）应用的 PBM 输送方法。iPBM 和 tcPBM（脊髓 24 mW/cm2，每天 1 分钟（1.44 J/cm2），持续 7 天）在 SCI 后 3 天增加了再生相关蛋白的活化，使 DRGN 中的 GAP43+ 轴突从 18.0% （对照组）增加到 41.4% ± 10.5（iPBM）和 45.8% ± 3.4（tcPBM）（p <0.05）。这与伤后6周时在运动功能和感觉功能恢复（p <0.01）、轴突再生（p <0.01）和病灶缩小（p <0.01）方面的显著改善相对应。我们的研究结果表明，无论是应用 iPBM 还是 tcPBM，PBM 都能在 SCI 后取得显著的治疗效果，并有可能开发用于 SCI 患者的临床治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

8.40

自引率

4.10%

发文量

150

审稿时长

12 weeks

期刊介绍： Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.