BACKGROUND AND PURPOSE Hypoxia and cerebral ischemia (HI) events are capable of triggering important changes in brain metabolism, including glucose metabolism abnormalities, which may be related to the severity of the insult. Using positron emission microtomography (microPET) with [18F]fluorodeoxyglucose (18F-FDG), this study proposes to assess abnormalities of brain glucose metabolism in adult rats previously submitted to the neonatal HI model. We hypothesize that cerebral metabolic outcomes will be associated with cognitive deficits and magnitude of brain injury. METHODS Seven-day-old rats were subjected to an HI model, induced by permanent occlusion of the right common carotid artery and systemic hypoxia. 18F-FDG-microPET was used to assess regional and whole brain glucose metabolism in rats at 60 postnatal days (PND 60). An interregional cross-correlation matrix was utilized to construct metabolic brain networks (MBN). Rats were also subjected to the Morris Water Maze (MWM) to evaluate spatial memory and their brains were processed for volumetric evaluation. RESULTS Brain glucose metabolism changes were observed in adult rats after neonatal HI insult, limited to the right brain hemisphere. However, not all HI animals exhibited significant cerebral hypometabolism. Hippocampal glucose metabolism was used to stratify HI animals into HI hypometabolic (HI-h) and HI non-hypometabolic (HI non-h) groups. The HI-h group had drastic MBN disturbance, cognitive deficit, and brain tissue loss, concomitantly. Conversely, HI non-h rats had normal brain glucose metabolism and brain tissue preserved, but also presented MBN changes and spatial memory impairment. Furthermore, data showed that brain glucose metabolism correlated with cognitive deficits and brain volume outcomes. CONCLUSIONS Our findings demonstrated that long-term changes in MBN drive memory impairments in adult rats subjected to neonatal hypoxic ischemia, using in vivo imaging microPET-FDG. The MBN analyses identified glucose metabolism abnormalities in HI non-h animals, which were not detected by conventional 18F-FDG standardized uptake value (SUVr) measurements. These animals exhibited a metabolic brain signature that may explain the cognitive deficit even with no identifiable brain damage.

中文翻译：

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新生鼠缺氧缺血后，代谢性脑网络的长期变化会驱动大鼠的记忆障碍。

背景和目的缺氧和脑缺血（HI）事件能够触发脑代谢的重要变化，包括葡萄糖代谢异常，这可能与损伤的严重程度有关。使用正电子发射显微照相术（microPET）和[18F]氟脱氧葡萄糖（18F-FDG），该研究建议评估先前提交给新生儿HI模型的成年大鼠的脑葡萄糖代谢异常。我们假设脑代谢结果将与认知缺陷和脑损伤的程度有关。方法对7日龄大鼠进行HI模型，该模型由右颈总动脉永久闭塞和全身性缺氧所致。18F-FDG-microPET用于评估出生后60天（PND 60）大鼠的局部和全脑葡萄糖代谢。使用区域间互相关矩阵来构建代谢性脑网络（MBN）。还对大鼠进行莫里斯水迷宫（MWM）评估空间记忆，并对其大脑进行处理以进行体积评估。结果新生鼠HI损伤后，在成年大鼠中观察到脑葡萄糖代谢变化，仅限于右脑半球。但是，并非所有的HI动物都表现出明显的脑代谢不足。海马葡萄糖代谢用于将HI动物分为HI低代谢组（HI-h）和HI非低代谢组（HI non-h）。HI-h组伴有剧烈的MBN紊乱，认知障碍和脑组织丢失。相反，HI非h大鼠脑葡萄糖代谢正常，脑组织得以保留，但MBN改变和空间记忆障碍。此外，数据显示，脑葡萄糖代谢与认知缺陷和脑容量结局相关。结论我们的研究结果表明，使用体内成像microPET-FDG可以对成年大鼠进行新生儿缺氧缺血后MBN的长期变化驱动记忆障碍。MBN分析确定了HI非h动物的葡萄糖代谢异常，而常规18F-FDG标准化摄取值（SUVr）测量未检测到异常。这些动物表现出新陈代谢的大脑特征，即使没有可识别的脑损伤也可以解释认知缺陷。使用microPET-FDG体内成像。MBN分析确定了HI非h动物的葡萄糖代谢异常，而常规18F-FDG标准化摄取值（SUVr）测量未检测到异常。这些动物表现出新陈代谢的大脑特征，即使没有可识别的脑损伤也可以解释认知缺陷。使用体内成像microPET-FDG。MBN分析确定了HI非h动物的葡萄糖代谢异常，而常规18F-FDG标准化摄取值（SUVr）测量未检测到异常。这些动物表现出新陈代谢的大脑特征，即使没有可识别的脑损伤也可以解释认知缺陷。