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.

中文翻译：

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植入式和经皮光生物调节促进神经再生和脊髓损伤后丧失功能的恢复


脊髓损伤 （SCI） 是造成严重且不可逆损伤的原因，没有有效的疗法来促进功能恢复。光生物调节 （PBM） 可能提供一种可行的治疗方法，使用红光或近红外光通过减轻神经炎症和防止神经元凋亡来促进 SCI 后的恢复。我们目前的研究旨在优化 PBM 剂量方案，并开发和验证侵入性 PBM 递送范式对 SCI 的疗效。使用原代成年大鼠背根神经节神经元 （DRGN） 培养损伤的血清撤断模型进行剂量优化研究。使用尸体建模开发和验证了植入式和经皮 PBM 递送方案。在成年大鼠 SCI 背柱挤压伤模型中研究 PBM 促进体内 SCI 后恢复的疗效。在 4 至 22 mW/cm2 之间实现了最佳的体外神经保护。每天 1 分钟 11 mW/cm2 （0.66 J/cm2） 在 5 天内使细胞活力增加 45% （p <0.0001），使神经突生长增加 25% （p <0.01）。使用扩散尖端光遗传学光纤开发了一种 PBM 侵入性应用的方法。PBM 的递送方法被开发并验证用于侵入性 （iPBM） 和无创 （transcutaneous） （tcPBM） 应用。iPBM 和 tcPBM（脊髓 24 mW/cm2，每天 1 分钟 （1.44 J/cm2），长达 7 天）在 SCI 后 3 天增加再生相关蛋白的激活，将 DRGN 中的 GAP43 + 轴突从 18.0%（对照）增加到 41.4% ± 10.5 （iPBM） 和 45.8% ± 3.4 （tcPBM） （p <0.05）。这对应于受伤后 6 周功能性运动和感觉功能恢复 （p <0.01） 、轴突再生 （p <0.01） 和病变大小减小 （p <0.01） 的显着改善。 我们的结果表明，PBM 在 SCI 后取得了显着的治疗益处，无论是使用 iPBM 还是 tcPBM 应用程序，并且有可能开发用于 SCI 患者的临床应用。