Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, United States of America; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15213, United States of America; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15213, United States of America.
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, United States of America; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15213, United States of America.
Exp Neurol. 2023 Nov;369:114544. doi: 10.1016/j.expneurol.2023.114544. Epub 2023 Sep 17.
Traumatic brain injury (TBI) causes neurobehavioral and cognitive impairments that negatively impact life quality for millions of individuals. Because of its pernicious effects, numerous pharmacological interventions have been evaluated to attenuate the TBI-induced deficits or to reinstate function. While many such pharmacotherapies have conferred benefits in the laboratory, successful translation to the clinic has yet to be achieved. Given the individual, medical, and societal burden of TBI, there is an urgent need for alternative approaches to attenuate TBI sequelae and promote recovery. Music based interventions (MBIs) may hold untapped potential for improving neurobehavioral and cognitive recovery after TBI as data in normal, non-TBI, rats show plasticity and augmented cognition. Hence, the aim of this study was to test the hypothesis that providing a MBI to adult rats after TBI would improve cognition, neurobehavior, and histological endpoints. Adult male rats received a moderate-to-severe controlled cortical impact injury (2.8 mm impact at 4 m/s) or sham surgery (n = 10-12 per group) and 24 h later were randomized to classical Music or No Music (i.e., ambient room noise) for 3 h/day from 19:00 to 22:00 h for 30 days (last day of behavior). Motor (beam-walk), cognitive (acquisition of spatial learning and memory), anxiety-like behavior (open field), coping (shock probe defensive burying), as well as histopathology (lesion volume), neuroplasticity (BDNF), and neuroinflammation (Iba1, and CD163) were assessed. The data showed that the MBI improved motor, cognitive, and anxiety-like behavior vs. No Music (p's < 0.05). Music also reduced cortical lesion volume and activated microglia but increased resting microglia and hippocampal BDNF expression. These findings support the hypothesis and provide a compelling impetus for additional preclinical studies utilizing MBIs as a potential efficacious rehabilitative therapy for TBI.
创伤性脑损伤（TBI）导致神经行为和认知障碍，使数百万人的生活质量受到负面影响。由于其有害影响，已经评估了许多药物干预措施来减轻 TBI 引起的缺陷或恢复功能。虽然许多这样的药物治疗在实验室中都有效果，但尚未成功转化为临床应用。鉴于 TBI 给个人、医疗和社会带来的负担，迫切需要寻找替代方法来减轻 TBI 后遗症并促进康复。基于音乐的干预（MBI）可能具有改善 TBI 后神经行为和认知恢复的未开发潜力，因为正常、非 TBI 大鼠的数据显示出可塑性和增强的认知能力。因此，本研究的目的是检验以下假设：在 TBI 后为成年大鼠提供 MBI 会改善认知、神经行为和组织学终点。成年雄性大鼠接受中度至重度皮质控制冲击伤（4 m/s 时 2.8mm 冲击）或假手术（每组 10-12 只），24 小时后随机分为古典音乐或无音乐（即环境房间噪音），每天 3 小时，从 19:00 到 22:00，持续 30 天（最后一天进行行为测试）。运动（走棒）、认知（空间学习和记忆的获得）、焦虑样行为（旷场）、应对（电击探针防御掩埋）以及组织病理学（病变体积）、神经可塑性（BDNF）和神经炎症（Iba1 和 CD163）。数据显示，MBI 改善了运动、认知和焦虑样行为，与无音乐组相比（p<0.05）。音乐还减少了皮质病变体积，激活了小胶质细胞，但增加了静止小胶质细胞和海马 BDNF 的表达。这些发现支持了假设，并为利用 MBI 作为 TBI 潜在有效康复治疗的进一步临床前研究提供了有力的动力。
