Nerve Wrap for Local Delivery of FK506/Tacrolimus Accelerates Nerve Regeneration

作者：Bo Xiao, Firuz Feturi, An-Jey A. Su, Yolandi van der Merwe, Joshua M. Barnett, Kayvon Jabbari, Neil J. Khatter, Bing Li, Evan B. Katzel, Raman Venkataramanan, Mario G. Solari, William R. Wagner, Michael B. Steketee, Daniel J. Simons, Kia M. Washington · 发表于：International Journal of Molecular Sciences · 年份：2024 · DOI：10.3390/ijms25020847 · 被引用次数：12 · 研究领域：Nerve injury and regeneration、Wound Healing and Treatments、Nerve Injury and Rehabilitation

Peripheral nerve injuries (PNIs) occur frequently and can lead to devastating and permanent sensory and motor function disabilities. Systemic tacrolimus (FK506) administration has been shown to hasten recovery and improve functional outcomes after PNI repair. Unfortunately, high systemic levels of FK506 can result in adverse side effects. The localized administration of FK506 could provide the neuroregenerative benefits of FK506 while avoiding systemic, off-target side effects. This study investigates the utility of a novel FK506-impregnated polyester urethane urea (PEUU) nerve wrap to treat PNI in a previously validated rat infraorbital nerve (ION) transection and repair model. ION function was assessed by microelectrode recordings of trigeminal ganglion cells responding to controlled vibrissae deflections in ION-transected and -repaired animals, with and without the nerve wrap. Peristimulus time histograms (PSTHs) having 1 ms bins were constructed from spike times of individual single units. Responses to stimulus onsets (ON responses) were calculated during a 20 ms period beginning 1 ms after deflection onset; this epoch captures the initial, transient phase of the whisker-evoked response. Compared to no-wrap controls, rats with PEUU-FK506 wraps functionally recovered earlier, displaying larger response magnitudes. With nerve wrap treatment, FK506 blood levels up to six weeks were measured nearly at the limit of quantification (LOQ ≥ 2.0 ng/mL); whereas the drug concentrati...