Cerebral Metabolic Changes Related to Oxidative Metabolism in a Model of Bacterial Meningitis Induced by Lipopolysaccharide
- 185 Downloads
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 (PbtO2) were also monitored along with physiological variables including mean arterial pressure, blood glucose, lactate, and partial pressure of O2 and CO2. 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 PbtO2 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, PbtO2, 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.
KeywordsMeningitis Lipopolysaccharide Microdialysis Mitochondrial dysfunction
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 7.Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2015(9):CD004405.Google Scholar
- 16.Gardenfors A, Nilsson F, Skagerberg G, Ungerstedt U, Nordstrom CH. Cerebral physiological and biochemical changes during vasogenic brain oedema induced by intrathecal injection of bacterial lipopolysaccharides in piglets. Acta Neurochir (Wien). 2002;144(6):601-8; discussion 8-9.Google Scholar
- 19.Reinstrup P, Stahl N, Mellergard P, Uski T, Ungerstedt U, Nordstrom CH. Intracerebral microdialysis in clinical practice: baseline values for chemical markers during wakefulness, anesthesia, and neurosurgery. Neurosurgery. 2000;47(3):701-9; discussion 9-10.Google Scholar
- 29.Kaizaki A, Tien LT, Pang Y, Cai Z, Tanaka S, Numazawa S, et al. Celecoxib reduces brain dopaminergic neuronaldysfunction, and improves sensorimotor behavioral performance in neonatal rats exposed to systemic lipopolysaccharide. J Neuroinflammation. 2013;10:45.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Samuelsson C, Hillered L, Zetterling M, Enblad P, Hesselager G, Ryttlefors M, et al. Cerebral glutamine and glutamate levels in relation to compromised energy metabolism: a microdialysis study in subarachnoid hemorrhage patients. J Cereb Blood Flow Metab. 2007;27(7):1309–17.CrossRefPubMedGoogle Scholar
- 31.Ungerstedt U, Bäckström T, Hallstrom A. Microdialysis in normal and injured human brain. In: Kinney JM, Tucker HN, editors. Physiology, stress and malnutrition: functional correlates, nutritional intervention. New York: Lippincott-Raven; 1997. p. 361–74.Google Scholar
- 34.Mills EL, Kelly B, Logan A, Costa ASH, Varma M, Bryant CE, et al. Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages. Cell. 2016;167(2):457-70 e13.Google Scholar