Clinical Neuroscience, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.
Behav Brain Res. 2010 Apr 2;208(2):609-18. doi: 10.1016/j.bbr.2010.01.007. Epub 2010 Jan 18.
Neuronal losses are observed in the brain after neonatal hypoxia-ischemia (HI) however few studies have examined the effects of HI on specific neuronal phenotypes and their possible contribution to behavioural outcomes. In the present study we examined whether postnatal day 3 (P3) HI alters numbers of corticotropin-releasing factor (CRF) and neuropeptide-Y (NPY) neurons in the paraventricular nucleus of the hypothalamus (PVN), the bed nucleus of the stria terminalis (BNST) and the amygdala, 1 (P10) and 6 (P45) weeks after P3 HI. A significant reduction in the number of CRF-positive neurons in the PVN, central nucleus of the amygdala (CeA) and BNST ipsilateral to the carotid ligation 1 and 6 weeks after P3 HI was observed. There was also a significant reduction in the number of NPY-positive neurons in the PVN, amygdala and BNST ipsilateral to the carotid ligation 1 week after P3 HI. However after 6 weeks, only the number of PVN NPY-positive neurons decreased significantly. At 6 weeks post-insult, the number of CeA CRF-positive neurons was inversely associated with locomotor activity and exploratory behaviour in an open field. In contrast, no significant correlations between neuronal counts and early neurodevelopment tests performed on P10 were observed. Thus after P3 HI persistent losses of CRF- and NPY-positive neurons occur and the loss of CeA CRF neurons may provide a central anatomical mechanism underlying neurobehavioural deficits observed 6 weeks after P3 HI.
新生大鼠缺氧缺血（HI）后脑内可观察到神经元丢失，但很少有研究探讨 HI 对特定神经元表型的影响及其对行为结果的可能贡献。本研究探讨了新生大鼠 HI 后第 3 天（P3）是否改变下丘脑室旁核（PVN）、终纹床核（BNST）和杏仁核内促肾上腺皮质激素释放因子（CRF）和神经肽 Y（NPY）神经元的数量，分别在 P3 HI 后 1 周（P10）和 6 周（P45）进行检测。结果发现，P3 HI 后 1 周和 6 周，与颈动脉结扎同侧的 PVN、杏仁核中央核（CeA）和 BNST 中 CRF 阳性神经元数量明显减少。P3 HI 后 1 周，与颈动脉结扎同侧的 PVN、杏仁核和 BNST 中 NPY 阳性神经元数量也明显减少。然而，6 周后，仅 PVN NPY 阳性神经元数量显著减少。在损伤后 6 周，CeA CRF 阳性神经元的数量与旷场实验中的运动活动和探索行为呈负相关。相比之下，在 P10 进行的早期神经发育测试与神经元计数之间没有观察到显著相关性。因此，P3 HI 后持续发生 CRF 和 NPY 阳性神经元丢失，而 CeA CRF 神经元丢失可能为 P3 HI 后 6 周观察到的神经行为缺陷提供了一个中枢解剖学机制。
