Huppertz-Kessler Christina J, Poeschl Johannes, Hertel Richard, Unsicker Klaus, Schenkel Johannes
Division of Neonatology, Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany.
Brain Dev. 2012 Apr;34(4):274-9. doi: 10.1016/j.braindev.2011.07.008. Epub 2011 Aug 20.
Stress and environmental perturbations influence postnatal brain development and may account for the high disability rates of preterm survivors following intensive care treatment. This study aims to investigate the impact of early environmental factors on the monoaminergic neurotransmitter system in the developing rat brain by using an innovative neonatal stress model.
After birth, in the experimental groups newborn rats were separated from their mothers and exposed to different stressful stimuli four times a day on day P0 to P6 for 10 min each. To mimic intensive care treatment, the stress protocol applied environmental factors like bright light, noise, and low temperature alternating with pain and handling stress at day- and night-time in a varying sequence. The non-stressed control mothers and litters were left completely undisturbed until sacrificing on day P7 or P20.
Brains of stressed animals revealed significantly higher levels of norepinephrine (NE) and dopamine (DA) as determined by HPLC-ED and electrochemical detection at day P7 as compared to controls. When returned to their mothers' undisturbed care, juvenile rats at day P20 still showed higher (yet statistically not significant) concentrations of NE and DA in brain. The stressed animals gained less weight with significantly lower body weights at day P7 compared to controls. Their mothers developed various forms of stressed behaviour.
A novel animal model for postnatal intensive care stress was established leading to changes in brain monoamine levels of newborn rats, while undisturbed maternal care seems to moderate the stress effects subsequently.
压力和环境扰动会影响出生后脑的发育,这可能是重症监护治疗后早产幸存者高致残率的原因。本研究旨在通过使用一种创新的新生动物应激模型,研究早期环境因素对发育中大鼠脑内单胺能神经递质系统的影响。
出生后,在实验组中,新生大鼠与母亲分离,并在出生后第0天至第6天每天接受4次不同的应激刺激,每次10分钟。为模拟重症监护治疗,应激方案采用了如强光、噪音和低温等环境因素,并在白天和晚上以不同顺序交替施加疼痛和处理应激。未受应激的对照母鼠和幼崽在出生后第7天或第20天处死前完全不受干扰。
通过高效液相色谱-电化学检测法(HPLC-ED)测定,与对照组相比,应激动物在出生后第7天的脑中去甲肾上腺素(NE)和多巴胺(DA)水平显著升高。当回到母亲不受干扰的照料下时,出生后第20天的幼鼠脑中NE和DA的浓度仍较高(但无统计学意义)。与对照组相比,应激动物体重增加较少,在出生后第7天体重显著较低。它们的母亲出现了各种应激行为。
建立了一种新的产后重症监护应激动物模型,该模型导致新生大鼠脑单胺水平发生变化,而不受干扰的母性照料似乎随后会减轻应激影响。