Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Department of Physical Therapy, Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Canada.
Brain Behav Immun. 2021 Mar;93:55-65. doi: 10.1016/j.bbi.2020.12.013. Epub 2020 Dec 21.
The inflammatory response following spinal cord injury is associated with increased tissue damage and impaired functional recovery. However, inflammation can also promote plasticity and the secretion of growth-promoting substances. Previously we have shown that inducing inflammation with a systemic injection of lipopolysaccharide in the chronic (8 weeks) stage of spinal cord injury enhances neuronal sprouting and the efficacy of rehabilitative training in rats. Here, we tested whether administration of lipopolysaccharide in female rats in the subacute (10 days) stage of spinal cord injury would have a similar effect. Since the lesioned environment is already in a pro-inflammatory state at this earlier time after injury, we hypothesized that triggering a second immune response may not be beneficial for recovery. Contrary to our hypothesis, we found that eliciting an inflammatory response 10 days after spinal cord injury enhanced the recovery of the ipsilesional forelimb in rehabilitative training. Compared to rats that received rehabilitative training without treatment, rats that received systemic lipopolysaccharide showed restored motor function without the use of compensatory strategies that translated beyond the trained task. Furthermore, lipopolysaccharide treatment paradoxically promoted the resolution of chronic neuroinflammation around the lesion site. Unfortunately, re-triggering a systemic immune response after spinal cord injury also resulted in a long-term increase in anxiety-like behaviour.
脊髓损伤后的炎症反应与组织损伤增加和功能恢复受损有关。然而，炎症也可以促进可塑性和生长促进物质的分泌。我们之前已经表明，在脊髓损伤的慢性（8 周）阶段通过全身注射脂多糖诱导炎症可以增强神经元的发芽和大鼠康复训练的效果。在这里，我们测试了在脊髓损伤后的亚急性（10 天）阶段向雌性大鼠中给予脂多糖是否会产生类似的效果。由于在损伤后更早的时间，损伤环境已经处于促炎状态，我们假设引发第二次免疫反应可能不利于恢复。与我们的假设相反，我们发现，在脊髓损伤后 10 天引发炎症反应可以增强康复训练中同侧前肢的恢复。与未接受治疗的接受康复训练的大鼠相比，接受全身脂多糖治疗的大鼠在不使用超越训练任务的代偿策略的情况下恢复了运动功能。此外，脂多糖治疗反常地促进了损伤部位周围慢性神经炎症的消退。不幸的是，在脊髓损伤后再次引发全身免疫反应也会导致长期焦虑样行为增加。
