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重度创伤性脑损伤对新生和幼年猪脑多巴胺能活性的年龄依赖性影响。

Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs.

作者信息

Walter Bernd, Brust Peter, Füchtner Frank, Müller Marco, Hinz Rainer, Kuwabara Hiroto, Fritz Harald, Zwiener Ulrich, Bauer Reinhard

机构信息

Department of Neurosurgery, Friedrich Schiller University Jena, Germany.

出版信息

J Neurotrauma. 2004 Aug;21(8):1076-89. doi: 10.1089/0897715041651024.

Abstract

There is evidence that the dopaminergic system is sensitive to traumatic brain injury (TBI). However, the age-dependency of this sensitivity has not been studied together with brain oxidative metabolism. We postulate that the acute effects of severe TBI on brain dopamine turnover are age-dependent. Therefore 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with Positron-Emission-Tomography (PET) was used to estimate the activity of the aromatic amino acid decarboxylase (AADC) in the brain of 11 newborn piglets (7-10 days old) and nine juvenile pigs (6-7 weeks old). Six newborn and five juvenile animals were subjected to a severe fluid-percussion (FP) induced TBI. The remaining animals were used as sham operated untreated control groups. Simultaneously, the regional cerebral blood flow (CBF) was measured with colored microspheres and the cerebral metabolic rates of oxygen and glucose were determined. At 1 h after FP-TBI, [18F]FDOPA was infused and PET scanning was performed for 2 h. At 2 h after FP-TBI administration, a second series of measurements of physiological values including CBF and brain oxidative metabolism data had been obtained. Severe FP-TBI elicited a marked increase in the rate constant for fluorodopamine production (k3FDOPA) in all brain regions of newborn piglets studied by between 97% (mesencephalon) and 143% (frontal cortex) (p < 0.05). In contrast, brain hemodynamics and cerebral oxidative metabolism remained unaltered after TBI. Furthermore, the permeability-surface area product of FDOPA (PSFDOPA) was unchanged. In addition, regional blood flow differences between corresponding ipsi- and contralateral brain regions did not occur after TBI. Thus, it is suggested that severe FP-TBI induces an upregulation of AADC activity of newborn piglets that is not related to alterations in brain oxidative metabolism.

摘要

有证据表明多巴胺能系统对创伤性脑损伤(TBI)敏感。然而,这种敏感性的年龄依赖性尚未与脑氧化代谢一起进行研究。我们推测严重TBI对脑多巴胺周转的急性影响具有年龄依赖性。因此,使用18F标记的6-氟-L-3,4-二羟基苯丙氨酸(FDOPA)结合正电子发射断层扫描(PET)来估计11只新生仔猪(7-10日龄)和9只幼年猪(6-7周龄)脑中芳香族氨基酸脱羧酶(AADC)的活性。6只新生动物和5只幼年动物接受了严重的液体冲击(FP)诱导的TBI。其余动物用作假手术未治疗的对照组。同时,用彩色微球测量局部脑血流量(CBF),并测定脑氧代谢率和葡萄糖代谢率。在FP-TBI后1小时,注入[18F]FDOPA并进行2小时的PET扫描。在给予FP-TBI后2小时,获得了包括CBF和脑氧化代谢数据在内的第二系列生理值测量结果。严重的FP-TBI使所研究的新生仔猪所有脑区的氟多巴胺生成速率常数(k3FDOPA)显著增加,增加幅度在97%(中脑)至143%(额叶皮质)之间(p<0.05)。相比之下,TBI后脑血流动力学和脑氧化代谢未发生改变。此外,FDOPA的通透表面积乘积(PSFDOPA)未改变。另外,TBI后相应同侧和对侧脑区之间未出现局部血流差异。因此,提示严重的FP-TBI诱导新生仔猪AADC活性上调,这与脑氧化代谢的改变无关。

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