Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, University of Perugia, Perugia, Italy; GeBiSa, Research Foundation, Perugia, Italy; Centro Europeo per la Medicina e la Ricerca (CEMER), Perugia, Italy.
Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, University of Perugia, Perugia, Italy.
Neurosci Lett. 2021 Jan 10;741:135459. doi: 10.1016/j.neulet.2020.135459. Epub 2020 Oct 24.
Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) are crucial for the peripheral and central nervous system development, respectively, and differential brain and blood levels in Intra Uterine Growth Restriction (IUGR) and prematurity have been found. As reduced growth of brain regions, measured at 30-40 days of postnatal period, has been demonstrated in preterm and IUGR neonates who showed impaired neuro-development at two years of age, in this study, the levels of NGF and BDNF were evaluated in the urine samples of 30-40 day-old subjects who were full-term, preterm and IUGR and showed a normal or an abnormal neuro-development at follow up after two years. Neurotrophins were measured concurrently with volumes of whole brain, thalamus, frontal cortex and cerebellum. Values were then correlated with later neuro-developmental outcome. Biochemical parameters and cerebral volumes were assessed using colorimetric ELISA kits and three-dimensional ultra-sonography (3DUS), respectively. Neuro-development was estimated using the Griffiths-II test. Urinary NGF and brain volumes significantly correlated and were lower in preterm and IUGR subjects characterized by poor neuro-development. No differences were seen in the case of BDNF. The present investigation demonstrates, for the first time, the strong and direct association of NGF with brain growth at the initial phase of the postnatal period and with neuro-developmental outcome in later life. Remarkably, urinary NGF may be suggested as an early prognostic indicator of high long-term risk of motor and cognitive impairment in IUGR and preterm neonates.
神经生长因子(NGF)和脑源性神经营养因子(BDNF)分别对周围和中枢神经系统的发育至关重要,在宫内生长受限(IUGR)和早产中发现了不同的大脑和血液水平。由于在表现出两年后神经发育受损的早产儿和 IUGR 新生儿中,在出生后 30-40 天期间已经证明大脑区域的生长减少,因此在本研究中,评估了 30-40 天龄的足月、早产和 IUGR 受试者的尿液样本中的 NGF 和 BDNF 水平,他们在两年后的随访中表现出正常或异常的神经发育。神经递质与大脑整体、丘脑、额叶皮层和小脑的体积同时进行测量。然后将这些值与以后的神经发育结果相关联。生化参数和脑体积分别使用比色 ELISA 试剂盒和三维超声(3DUS)进行评估。神经发育使用 Griffiths-II 测试进行评估。尿 NGF 和脑体积与神经发育结果显著相关,在神经发育不良的早产儿和 IUGR 受试者中较低。BDNF 没有差异。本研究首次证明了 NGF 在出生后早期与大脑生长以及以后生活中的神经发育结果之间的强而直接的关联。值得注意的是,尿 NGF 可作为 IUGR 和早产儿中运动和认知障碍长期高风险的早期预后指标。