1University of Alberta, Edmonton, AB, Canada.
Neurorehabil Neural Repair. 2014 May;28(4):395-404. doi: 10.1177/1545968313517758. Epub 2013 Dec 27.
Rehabilitation aids recovery from stroke in animal models, including in intracerebral hemorrhage (ICH). Sometimes, rehabilitation lessens brain damage.
We tested whether rehabilitation improves recovery and reduces perihematoma neuronal death. We also evaluated whether rehabilitation influences iron toxicity and inflammation, mediators of secondary degeneration after ICH.
Rats were trained to retrieve food pellets in a staircase apparatus and later subjected to striatal ICH (via collagenase infusion). After 1 week, they were given either enriched rehabilitation (ER), including reach training with group housing and environmental enrichment, or control treatment (group housing). Rats in the first experiment were treated for 2 weeks, functionally assessed, and killed humanely at 1 month to determine brain levels of nonheme iron. A second experiment used a similar approach, except that animals were euthanized at 14 days to evaluate perihematoma neuronal death (FluoroJade), iron distribution (Perls), and astrocyte (GFAP) and microglia (Iba-1) activity. A third experiment measured levels of iron-binding proteins (ferritin and transferrin) at 14 days.
Striatal ICH caused functional impairments, which were significantly improved with ER. The ICH caused delayed perihematoma neuronal death, which ER significantly reduced. Hemispheric iron levels, the amount of iron-binding proteins, and perihematoma astrocytes and microglia numbers were significantly elevated after ICH (vs normal side) but were not affected by ER.
Rehabilitation is an effective behavioral and neuroprotective strategy for ICH. Neither effect appears to stem from influencing iron toxicity or inflammation. Thus, additional work must identify underlying mechanisms to help further therapeutic gains.
康复辅助动物模型（包括脑出血）中的中风恢复。有时，康复可以减轻脑损伤。
我们测试了康复是否可以改善恢复并减少血肿周围神经元死亡。我们还评估了康复是否会影响铁毒性和炎症，这是脑出血后继发性变性的介质。
大鼠接受了在楼梯设备中取食丸的训练，随后接受纹状体脑出血（通过胶原酶输注）。1 周后，它们接受了丰富的康复治疗（包括与群体饲养和环境丰富相结合的伸展训练）或对照治疗（群体饲养）。在第一个实验中，大鼠接受了 2 周的治疗，然后进行功能评估，并在 1 个月时人道处死，以确定大脑中非血红素铁的水平。第二个实验采用了类似的方法，只是动物在 14 天时被安乐死，以评估血肿周围神经元死亡（FluoroJade）、铁分布（Perls）以及星形胶质细胞（GFAP）和小胶质细胞（Iba-1）的活性。第三个实验在 14 天时测量了铁结合蛋白（铁蛋白和转铁蛋白）的水平。
纹状体脑出血导致了功能障碍，而康复治疗显著改善了这些功能障碍。脑出血导致了血肿周围神经元的延迟性死亡，而康复治疗显著减少了这种死亡。半脑铁水平、铁结合蛋白的含量以及血肿周围的星形胶质细胞和小胶质细胞数量在脑出血后（与正常侧相比）显著升高，但不受康复治疗的影响。
康复是脑出血的有效行为和神经保护策略。这两种效果似乎都不是通过影响铁毒性或炎症来实现的。因此，必须开展更多的工作来确定潜在的机制，以帮助进一步获得治疗效果。
