Girard Sylvie, Murray Katie N, Rothwell Nancy J, Metz Gerlinde A S, Allan Stuart M
Faculty of Life Science, University of Manchester, Manchester, UK.
Faculty of Life Science, University of Manchester, Manchester, UK.
Behav Brain Res. 2014 Aug 15;270(100):18-28. doi: 10.1016/j.bbr.2014.05.008. Epub 2014 May 10.
Cerebral ischemia is one of the most common causes of disabilities in adults and leads to long-term motor and cognitive impairments with limited therapeutic possibilities. Treatment options have proven efficient in preclinical models of cerebral ischemia but have failed in the clinical setting. This limited translation may be due to the suitability of models used and outcomes measured as most studies have focused on the early period after injury with gross motor scales, which have limited correlation to the clinical situation. The aim of this study was to determine long-term functional outcomes after cerebral ischemia in rats, focusing on fine motor function, social and depressive behavior as clinically relevant measures. A secondary objective was to evaluate the effects of an anti-inflammatory treatment (interleukin-1 receptor antagonist (IL-1Ra)) on functional recovery and compensation. Infarct volume was correlated with long-term (25 days) impairments in fine motor skills, but not with emotional components of behavior. Motor impairments could not be detected using conventional neurological tests and only detailed analysis allowed differentiation between recovery and compensation. Acute systemic administration of IL-1Ra (at reperfusion) led to a faster and more complete recovery, but delayed (24h) IL-1Ra treatment had no effect. In summary functional assessment after brain injury requires detailed motor tests in order to address long-term impairments and compensation processes that are mediated by intact tissues. Functional deficits in skilled movement after brain injury represent ideal predictors of long-term outcomes and should become standard measures in the assessment of preclinical animal models.
脑缺血是成人残疾的最常见原因之一，会导致长期的运动和认知障碍，且治疗选择有限。治疗方案在脑缺血的临床前模型中已证明有效，但在临床环境中却失败了。这种有限的转化可能是由于所用模型的适用性和所测量的结果，因为大多数研究都集中在损伤后的早期，使用的是粗略的运动量表，而这些量表与临床情况的相关性有限。本研究的目的是确定大鼠脑缺血后的长期功能结果，重点关注精细运动功能、社交和抑郁行为等与临床相关的指标。第二个目标是评估抗炎治疗（白细胞介素-1受体拮抗剂（IL-1Ra））对功能恢复和代偿的影响。梗死体积与精细运动技能的长期（25天）损伤相关，但与行为的情绪成分无关。使用传统的神经学测试无法检测到运动损伤，只有详细分析才能区分恢复和代偿。急性全身给予IL-1Ra（再灌注时）可导致更快、更完全的恢复，但延迟（24小时）给予IL-1Ra治疗则无效。总之，脑损伤后的功能评估需要详细的运动测试，以解决由完整组织介导的长期损伤和代偿过程。脑损伤后熟练运动的功能缺陷是长期结果的理想预测指标，应成为临床前动物模型评估的标准测量方法。
