目的 研究长期丰富环境对促进小鼠缺血性脑损伤后运动、社交功能恢复的作用。方法 成年雄性ICR小鼠16只,复制大脑中动脉永久性栓塞模型。术后第1天将小鼠分为丰富环境组(n=8)和标准环境组(n=8)。术后7 d、14 d、21 d、28 d对小鼠进行改良神经损害严重程度评分(mNSS),进行疲劳转棒仪、聪明笼子检测。结果 术后28 d,丰富环境组mNSS评分与转棒疲劳试验结果优于标准环境组(t>2.927, P<0.05)。一般运动试验中,术后14~28 d,丰富环境组在聪明笼子中间区域出现的时间长于标准环境组(t>2.480, P<0.05);社交行为试验中,术后7~28 d,丰富环境组比标准环境组表现出对陌生小鼠更感兴趣的趋势,但无显著性差异(P>0.05);术后14~28 d,丰富环境组出现在中间区域的时间明显长于标准环境组(t>3.472, P<0.01);术后14 d在聪明笼子中的移动速度高于标准环境组(P<0.05)。结论 丰富环境有助于小鼠缺血性脑损伤后运动功能恢复,并可能促进其社交功能恢复。
Objective To explore the role of long-term enriched environment in promoting the recovery of motor and social function in mice after ischemic brain injury. Methods Sixteen adult male ICR mice underwent permanent middle cerebral artery occlusion (MCAO). The first day after operation, they were divided into enriched environment group (n=8) and standard condition group (n=8). The mice were tested with modified Neurological Severity Score (mNSS), rotarod test and smart cage 7, 14, 21, 28 days after modeling. Results The score of mNSS and the result of rotarod test improved more in the enriched environment group than in the standard condition group 28 days after MCAO (t>2.927, P<0.05). The occupancy time in the middle of smart cage was longer in the enriched environment group than in the standard condition group 7 to 28 days after MCAO (t>2.480, P<0.05) in the general move test. There was a trend of being more interested in strange mice in the enriched environment group than in the standard condition group, but the difference was not statistically significant (P>0.05) in the social behavior test; however, the occupancy time in the middle of smart cage was longer in the enriched environment group than in the standard condition group 14 to 28 days after MCAO (t>3.472, P<0.01), and the velocity of moving was higher 14 days after MCAO (P<0.05). Conclusion Enriched environment could promote the recovery of motor function, somehow of social function, in mice after ischemic brain injury.
[1] Faralli A, Bigoni M, Mauro A, et al. Noninvasive strategies to promote functional recovery after stroke [J]. Neural Plast, 2013, 2013: 854597.
[2] White JH, Alborough K, Janssen H, et al. Exploring staff experience of an "enriched environment" within stroke rehabilitation: a qualitative sub-study [J]. Disabil Rehabil, 2014, 36(21): 1783-1789.
[3] De Wit L, Putman K, Dejaeger E, et al. Use of time by stroke patients: a comparison of four European rehabilitation centers [J]. Stroke, 2005, 36(9): 1977-1983.
[4] Nygren J, Wieloch T. Enriched environment enhances recovery of motor function after focal ischemia in mice, and downregulates the transcription factor NGFI-A [J]. J Cereb Blood Flow Metab, 2005, 25(12): 1625-1633.
[5] Johansson BB. Functional and cellular effects of environmental enrichment after experimental brain infarcts [J]. Restor Neurol Neurosci, 2004, 22(3-5): 163-174.
[6] Quattromani MJ, Cordeau P, Ruscher K, et al. Enriched housing down-regulates the Toll-like receptor 2 response in the mouse brain after experimental stroke [J]. Neurobiol Dis, 2014, 66: 66-73.
[7] Clarke J, Langdon KD, Corbett D. Early poststroke experience differentially alters periinfarct layer II and III cortex [J]. J Cereb Blood Flow Metab, 2014, 34(4): 630-637.
[8] Yu K, Wu Y, Hu Y, et al. Prior exposure to enriched environment reduces nitric oxide synthase after transient MCAO in rats [J]. Neurotoxicology, 2013, 39: 146-152.
[9] Huang J, Li Y, Tang Y, et al. CXCR4 antagonist AMD3100 protects blood-brain barrier integrity and reduces inflammatory response after focal ischemia in mice [J]. Stroke, 2013, 44(1): 190-197.
[10] Mao L, Jia J, Zhou X, et al. Delayed administration of a PTEN inhibitor BPV improves functional recovery after experimental stroke [J]. Neuroscience, 2013, 231: 272-281.
[11] Bouet V, Freret T, Toutain J, et al. Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse [J]. Exp Neurol, 2007, 203(2): 555-567.
[12] Xiong X, White RE, Xu L, et al. Mitigation of murine focal cerebral ischemia by the hypocretin/orexin system is associated with reduced inflammation [J]. Stroke, 2013, 44(3): 764-770.
[13] Xiong X, Barreto GE, Xu L, et al. Increased brain injury and worsened neurological outcome in interleukin-4 knockout mice after transient focal cerebral ischemia [J]. Stroke, 2011, 42(7): 2026-2032.
[14] Khroyan TV, Zhang J, Yang L, et al. Rodent motor and neuropsychological behaviour measured in home cages using the integrated modular platform SmartCage [J]. Clin Exp Pharmacol Physiol, 2012, 39(7): 614-622.
[15] Keyvani K, Sachser N, Witte OW, et al. Gene expression profiling in the intact and injured brain following environmental enrichment [J]. J Neuropathol Exp Neurol, 2004, 63(6): 598-609.
[16] Rampon C, Jiang CH, Dong H, et al. Effects of environmental enrichment on gene expression in the brain [J]. Proc Natl Acad Sci U S A, 2000, 97(23): 12880-12884.
[17] Ruscher K, Johannesson E, Brugiere E, et al. Enriched environment reduces apolipoprotein E (ApoE) in reactive astrocytes and attenuates inflammation of the peri-infarct tissue after experimental stroke [J]. J Cereb Blood Flow Metab, 2009, 29(11): 1796-1805.
[18] 宋名杨, 朱路文, 叶涛, 等. 丰富环境促进缺血缺氧性脑损伤修复的研究进展[J]. 中国康复理论与实践, 2016, 22(1): 61-64.
[19] Wieloch T, Nikolich K. Mechanisms of neural plasticity following brain injury [J]. Curr Opin Neurobiol, 2006, 16(3): 258-264.
[20] 李娴,谢斌. 丰富环境与脑卒中康复[J]. 中国康复理论与实践, 2012, 18(1): 47-52.
[21] Olson AK, Eadie BD, Ernst C, et al. Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways [J]. Hippocampus, 2006, 16(3): 250-260.
[22] Yang L, Zou B, Xiong X, et al. Hypocretin/orexin neurons contribute to hippocampus-dependent social memory and synaptic plasticity in mice [J]. J Neurosci, 2013, 33(12): 5275-5284.
[23] Vazquez-DeRose J, Stauber G, Khroyan TV, et al. Retrodialysis of N/OFQ into the nucleus accumbens shell blocks cocaine-induced increases in extracellular dopamine and locomotor activity [J]. Eur J Pharmacol, 2013, 699(1-3): 200-206.
[24] Bevins RA, Besheer J. Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study 'recognition memory' [J]. Nat Protoc, 2006, 1(3): 1306-1311.
[25] White JH, Bartley E, Janssen H, et al. Exploring stroke survivor experience of participation in an enriched environment: a qualitative study [J]. Disabil Rehabil, 2015, 37(7): 593-600.