Windle Victoria, Power Alexandra, Corbett Dale
BioMedical Sciences, Faculty of Medicine, Memorial University, St John's, NL, Canada.
Eur J Neurosci. 2007 Oct;26(7):1822-31. doi: 10.1111/j.1460-9568.2007.05799.x. Epub 2007 Sep 14.
Previous studies have suggested that increased norepinephrine plays an important role in recovery of function after brain injury; however, the majority of these studies used drugs that are known to also affect other monoamines to increase or decrease norepinephrine. The purpose of the present study was to determine if norepinephrine is required to promote recovery after ischemia. A form of enriched rehabilitation was used to rehabilitate animals after ischemia and the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine was used to selectively destroy norepinephrine projections from the locus coeruleus. Three sensorimotor tests were used to evaluate the recovery of the animals. Depletion of norepinephrine improved sensorimotor recovery in standard-housed animals and did not impede recovery in the rehabilitation groups. Dopamine beta hydroxylase staining was used to confirm N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine-depleted terminal norepinephrine levels. The amount of norepinephrine terminal staining negatively correlated with recovery of function in the staircase test after ischemia. In addition, enriched rehabilitation increased, but depletion of norepinephrine had no effect on, brain-derived neurotrophic factor protein levels, which have also been linked to improved recovery of function. Together the above findings question the previously postulated role of norepinephrine in recovery of function after stroke.
先前的研究表明，去甲肾上腺素水平升高在脑损伤后的功能恢复中起重要作用；然而，这些研究大多使用了已知会影响其他单胺类物质从而增加或减少去甲肾上腺素的药物。本研究的目的是确定缺血后促进恢复是否需要去甲肾上腺素。采用一种强化康复形式对缺血后的动物进行康复治疗，并使用神经毒素N-（2-氯乙基）-N-乙基-2-溴苄胺选择性地破坏蓝斑核发出的去甲肾上腺素投射。使用三项感觉运动测试来评估动物的恢复情况。去甲肾上腺素耗竭改善了标准饲养动物的感觉运动恢复，且并未阻碍康复组的恢复。使用多巴胺β羟化酶染色来确认N-（2-氯乙基）-N-乙基-2-溴苄胺导致的终末去甲肾上腺素水平降低。缺血后在阶梯试验中，去甲肾上腺素终末染色量与功能恢复呈负相关。此外，强化康复可提高脑源性神经营养因子蛋白水平，但去甲肾上腺素耗竭对其没有影响，脑源性神经营养因子蛋白水平也与功能恢复改善有关。上述研究结果共同对先前推测的去甲肾上腺素在中风后功能恢复中的作用提出了质疑。
