Developmental and regional differences in nitric oxide synthase activity and blood flow in the sheep brain.
Developmental and regional differences in nitric oxide synthase activity and blood flow in the sheep brain.
复制标题
绵羊大脑中一氧化氮合酶活性和血流量的发育和区域差异。
DOI：
10.1097/00004647-199701000-00014
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Koehler,RC
中科院分区：
文献类型：
--
作者：
Northington,FJ;Tobin,JR;Harris,AP;Traystman,RJ;Koehler,RC
一氧化氮合酶（NOS）参与脑血流和神经递质释放的调节，并作为谷氨酸能和胆碱能系统的第二信使。在大鼠中描述了NOS活性的发育差异，但在妊娠期较长、出生时脑分叶较大的物种中却没有。我们通过将[14C] l -精氨酸转化为[14C] l -瓜氨酸的方法，在妊娠70、92、110和135天（妊娠期= 145天）的绵羊大脑8个区域的50毫克组织样本中检测NOS活性；新生儿（<7天）；和成年人来验证这个假设，即从妊娠中期到成年，大脑中的NOS活动受到发育调节，并沿着神经轴成熟，与已知的脑血流和神经元活动的发展平行。NOS活性成熟的三种模式是明显的：妊娠70天前丘脑、小脑和延髓的NOS活性增加到或超过成人水平；海马体在70至92天之间增加到成人水平；92天后，大脑皮层和尾状核的水平上升到成年人的水平。此外，皮质NOS活性存在区域差异：在妊娠70天和92天，额叶皮质NOS活性大于顶叶或枕叶活性，在妊娠135天以及新生儿和成人中，皮质和尾状核活性超过大部分尾叶区域。妊娠92 ~ 135天区域皮质NOS活性增加4倍，与此期间脑血流量和耗氧量增加2倍相关。给予60 mg/kg ng -硝基- l -精氨酸甲基lester （L-NAME）抑制NOS活性，可使妊娠93天和133天的脑血流量减少27%和25%。虽然NOS活性的增加与CBF和cmoro2的增加并不是因果关系，但在妊娠的不同阶段，NOS活性的发展可能与突触和电活动的发展并行，参与成熟的脑血流调节模式的发展。
Nitric oxide synthase (NOS) participates in the regulation of cerebral blood flow and neurotransmitter release and as a second messenger of glutamatergic and cholinergic systems. Developmental differences in NOS activity have been described in the rat, but not in a species with longer gestation and a larger, lobulated brain at birth. We assayed NOS activity by conversion of [14C]L-arginine to [14C]L-citrulline in 50-mg tissue samples from eight brain regions in sheep at 70, 92, 110, and 135 days gestation (term = 145 days); newborns (<7 days); and adults to test the hypothesis that NOS activity in the brain is developmentally regulated from midgestation through adulthood and matures along the neuroaxis in parallel with the known development of cerebral blood flow and neuronal activity. Three patterns of maturation of NOS activity were evident: increasing to or exceeding adult levels before 70 days gestation in the thalamus, cerebellum, and medulla; increasing to adult levels between 70 and 92 days in the hippocampus; and increasing to adult levels after 92 days in the cortex and caudate. Additionally, there were regional differences in cortical NOS activity: at 70 and 92 days of gestation, frontal cortex NOS activity was greater than parietal or occipital activity, and at 135 days gestation and in the newborn and adult, cortical and caudate activity exceeded that in most of the more caudal regions. The up to fourfold increase in regional cortical NOS activity between 92 and 135 days gestation was associated with twofold increases in cerebral blood flow and oxygen consumption during this period. Inhibition of NOS activity with administration of 60 mg/kg ofNG-nitro-L-arginine methylester (L-NAME) resulted in 27% and 25% reductions in cerebral blood flow at 93 and 133 days gestation. While the associated increases in NOS activity with increases in CBF and CMRO2do not appear causative, at various points in gestation the development of NOS activity may participate in the development of mature patterns of cerebral blood flow regulation in parallel with development of synaptic and electrical activity.