Naureen Irum, Waheed Kh A Irfan, Rathore Ahsen W, Victor Suresh, Mallucci Conor, Goodden John R, Chohan Shahid N, Miyan Jaleel A
Faculty of Life Sciences, The University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK.
Childs Nerv Syst. 2014 Jul;30(7):1155-64. doi: 10.1007/s00381-014-2415-6. Epub 2014 Apr 15.
Hydrocephalus (HC) has a multifactorial and complex picture of pathophysiology due to aetiology, age at and duration since onset. We have previously identified distinctions in markers of cell death associated with different aetiologies. Here, we examined cerebrospinal fluid (CSF) from human HC neonates for cytokines to identify further distinguishing features of different aetiologies.
CSF was collected during routine lumbar puncture or ventricular tap from neonates with hydrocephalus, or with no neurological condition (normal controls). Total protein, Fas receptor, Fas ligand, stem cell factor (SCF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin growth factor-1 (IGF-1), tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured and compared between 8 unaffected and 28 HC neonatal CSF samples.
Total protein was significantly (P < 0.05) raised in late-onset hydrocephalus (LOH). Fas receptor was raised (P < 0.05) in post-haemorrhagic hydrocephalus (PHH) and spina bifida with hydrocephalus (SB/HC), but no difference in Fas ligand was found. SCF was raised (P < 0.05) in SB/HC. HGF was found in all HC and was increased (P < 0.01) in PHH. Increased VEGF was found in PHH (P < 0.01) and SB/HC (P < 0.05). Variable levels of IL-6, TNF-α and IGF-1 were found in all HC groups compared with none in normal.
LOH was unusual with significantly raised total protein indicating an inflammatory state. Increased Fas receptor, VEGF, IGF-1 and HGF suggest anti-apoptotic and repair mechanism activation. By contrast, elevated TNF-α and IL-6 indicate inflammatory processes in these neonatal brains. Taken with our previous study, these data indicate that different pathophysiology, inflammation and repair are occurring in HC of different aetiologies and that additional treatment strategies may benefit these infants in addition to fluid diversion.
由于病因、发病年龄及病程，脑积水（HC）具有多因素且复杂的病理生理情况。我们之前已确定与不同病因相关的细胞死亡标志物存在差异。在此，我们检测了人类HC新生儿的脑脊液（CSF）中的细胞因子，以确定不同病因的进一步区别特征。
在常规腰椎穿刺或脑室穿刺时，从患有脑积水的新生儿或无神经系统疾病的新生儿（正常对照）中收集CSF。测量并比较8份未受影响的和28份HC新生儿CSF样本中的总蛋白、Fas受体、Fas配体、干细胞因子（SCF）、肝细胞生长因子（HGF）、血管内皮生长因子（VEGF）、胰岛素生长因子-1（IGF-1）、肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）。
迟发性脑积水（LOH）中总蛋白显著升高（P < 0.05）。出血后脑积水（PHH）和脊柱裂合并脑积水（SB/HC）中Fas受体升高（P < 0.05），但Fas配体未发现差异。SB/HC中SCF升高（P < 0.05）。所有HC样本中均检测到HGF，且PHH中HGF升高（P < 0.01）。PHH中VEGF升高（P < 0.01），SB/HC中VEGF也升高（P < 0.05）。与正常样本中均未检测到相比，所有HC组中IL-6、TNF-α和IGF-1水平各不相同。
LOH情况少见，总蛋白显著升高表明存在炎症状态。Fas受体、VEGF、IGF-1和HGF升高提示抗凋亡和修复机制激活。相比之下，TNF-α和IL-6升高表明这些新生儿脑内存在炎症过程。结合我们之前的研究，这些数据表明不同病因的HC中存在不同的病理生理、炎症和修复情况，除了脑脊液分流外，额外的治疗策略可能使这些婴儿受益。
