University of Southern Denmark School of Medicine, Odense, Denmark.
Department of Neurosurgery, Odense University Hospital, Odense, Denmark.
Neurocrit Care. 2018 Dec;29(3):496-503. doi: 10.1007/s12028-018-0509-9.
Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis.
Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral microdialysis technique and included interstitial glucose, lactate, pyruvate, glutamate, and glycerol. The intracranial pressure (ICP) and brain tissue oxygen tension (PbtO) were also monitored along with physiological variables including mean arterial pressure, blood glucose, lactate, and partial pressure of O and CO. Pigs were monitored for 60 min at baseline and 240 min after LPS/NaCl injection.
After LPS injection, a significant increase in cerebral lactate/pyruvate ratio (LPR) compared to control group was registered (p = 0.01). This increase was due to a significant increased lactate with stable and normal values of pyruvate. No significant change in PbtO or ICP was registered. No changes in physiological variables were observed.
The metabolic changes after intracisternal LPS injection is compatible with disturbance in the oxidative metabolism and partly due to mitochondrial dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed by conventional intensive care monitoring.
在严重细菌性脑膜炎的病理生理学中，脑线粒体功能障碍很突出。在本研究中，我们假设在脑膜炎猪模型中脑室内注入脂多糖（LPS）后观察到的代谢变化与线粒体功能障碍一致，并且类似于细菌性脑膜炎患者的代谢模式。
8 头猪接受脑室内 LPS 注射，4 头猪接受脑室内生理盐水作为对照。通过脑室内微透析技术监测与能量代谢相关的生化变量，包括间质葡萄糖、乳酸、丙酮酸、谷氨酸和甘油。同时监测颅内压（ICP）和脑氧分压（PbtO）以及包括平均动脉压、血糖、乳酸和 O 和 CO 分压在内的生理变量。在 LPS/NaCl 注射前和注射后 60 分钟监测猪。
与对照组相比，LPS 注射后大脑乳酸/丙酮酸比值（LPR）显著升高（p=0.01）。这种增加是由于乳酸显著增加，而丙酮酸保持稳定和正常。PbtO 或 ICP 无明显变化。未观察到生理变量的变化。
脑室内 LPS 注射后的代谢变化与氧化代谢紊乱一致，部分原因是线粒体功能障碍导致大脑 LPR 增加，这是由于乳酸增加和丙酮酸、PbtO 和 ICP 正常。代谢模式类似于细菌性脑膜炎患者观察到的模式。代谢监测在这些患者中是可行的，以监测常规重症监护监测可能遗漏的脑代谢紊乱。
