Vasiljevic Brankica, Maglajlic-Djukic Svjetlana, Gojnic Miroslava, Stankovic Sanja, Ignjatovic Svetlana, Lutovac Dragana
Department of Neonatology, Institute of Gynecology and Obstetrics - Clinical Centre of Serbia, Belgrade, Serbia.
Pediatr Int. 2011 Aug;53(4):454-62. doi: 10.1111/j.1442-200X.2010.03290.x.
Pathogenesis of perinatal hypoxic-ischemic brain injury (HIE) is complex. In this study, we examined the role of neuroinflammation, oxidative stress and growth factors in perinatal hypoxic-ischemic brain damage.
Ninety neonates (>32 weeks' gestation) with perinatal HIE were enrolled prospectively. Perinatal HIE was categorized into three stages according to the Sarnat and Sarnat clinical scoring system and changes seen on amplitude integrated electroencephalography. Cerebrospinal fluid (CSF) for interleukin-6 (IL-6) and glutathione peroxidase analysis was taken in the first 48 h of life and subsequent CSF for neuron-specific enolase (NSE) and vascular endothelial growth factor (VEGF) analysis 72 h after birth. Neurodevelopmental outcome was assessed at 12 months of corrected gestational age using the Denver Developmental Screening Test.
Concentrations of NSE in CSF correlated with severity of HIE (P < 0.0001) and corresponded well with subsequent neurodevelopmental outcome. Concentrations of IL-6 in CSF were markedly increased in neonates with severe HIE (P < 0.0001) and those with subsequent neurological sequels, but were normal in the majority of neonates with mild and moderate HIE. Glutathione peroxidase activity in CSF was significant with the stage of HIE (P < 0.0001) and gestational age (P < 0.0001) and corresponded well with subsequent neurodevelopmental outcome. Advanced stage of HIE was associated with increased concentrations of VEGF in CSF (P < 0.0001). Neurological outcomes at 12 months of age correlated best with CSF level of NSE (P < 0.001) and IL-6 (P < 0.001).
Our results suggest that neuroinflammation plays a principal role in perinatal hypoxic-ischemic brain damage and we postulate that oxidative stress and upregulation of VEGF might be important contributing factors in the pathogenesis of hypoxic-ischemic brain injury, particularly in preterm neonates.
围产期缺氧缺血性脑损伤（HIE）的发病机制复杂。在本研究中，我们研究了神经炎症、氧化应激和生长因子在围产期缺氧缺血性脑损伤中的作用。
前瞻性纳入90例孕周>32周的围产期HIE新生儿。根据Sarnat和Sarnat临床评分系统以及振幅整合脑电图的变化，将围产期HIE分为三个阶段。在出生后的头48小时内采集脑脊液（CSF）用于白细胞介素-6（IL-6）和谷胱甘肽过氧化物酶分析，出生后72小时采集后续脑脊液用于神经元特异性烯醇化酶（NSE）和血管内皮生长因子（VEGF）分析。在矫正胎龄12个月时使用丹佛发育筛查测试评估神经发育结局。
脑脊液中NSE的浓度与HIE的严重程度相关（P<0.0001），并与随后的神经发育结局密切相关。重度HIE新生儿和有后续神经后遗症的新生儿脑脊液中IL-6的浓度显著升高（P<0.0001），但大多数轻度和中度HIE新生儿的IL-6浓度正常。脑脊液中的谷胱甘肽过氧化物酶活性与HIE阶段（P<0.0001）和胎龄（P<0.0001）显著相关，并与随后的神经发育结局密切相关。HIE晚期与脑脊液中VEGF浓度升高相关（P<0.0001）。12个月龄时的神经学结局与脑脊液中NSE水平（P<0.001）和IL-6水平（P<0.001）相关性最佳。
我们的结果表明，神经炎症在围产期缺氧缺血性脑损伤中起主要作用，我们推测氧化应激和VEGF的上调可能是缺氧缺血性脑损伤发病机制中的重要促成因素，尤其是在早产儿中。
