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Brain acidosis in experimental pneumococcal meningitis
N E Andersen1, J Gyring, A J Hansen
1Institute of General Physiology and Biophysics, Panum Institute, University of Copenhagen, Denmark.
Abstract:
Purulent meningitis is a serious disease that often has a lethal outcome or gives lasting complications due to brain damage. The processes causing brain dysfunction or damage are still not uncovered nor are the reasons for the characteristic increase of CSF lactate, or the decrease of glucose levels and of pH. We studied rabbits with experimentally induced purulent meningitis (Streptococcus pneumoniae). Ten hours after the inoculation into cisterna magna the rabbits developed symptoms of meningitis, with stiffness of the neck, tachypnea, and fever. The CSF level of lactate and the number of leukocytes were significantly increased and the glucose level was decreased. Brain interstitial pH, as measured by ion selective microelectrodes, was significantly decreased from the normal level of 7.4 to 6.9. The levels of energy metabolites in brain cortex, including glucose, were not different between controls and infected animals, and the lactate level was not elevated more than could have been explained by passive diffusion from the CSF. This shows that the brain tissue is not the source of CSF lactate nor the sink for glucose in CSF. The marked acidification of brain interstitial space and CSF demonstrates that purulent meningitis causes a significant disturbance of brain ion homeostasis that could be, at least in part, responsible for the brain dysfunction. We suggest that activated leukocytes consume CSF glucose and produce lactic acid and secrete protons, which causes the CSF and interstitial acidosis.
Insights
Purulent meningitis causes brain dysfunction by disrupting ion homeostasis. Activated leukocytes consume glucose and produce acid, leading to acidosis in the brain and cerebrospinal fluid (CSF).
Area of Science:
- Neurology
- Infectious Diseases
- Neuroscience
Background:
- Purulent meningitis is a severe condition with high mortality and neurological sequelae.
- The underlying mechanisms of brain dysfunction and characteristic cerebrospinal fluid (CSF) changes (lactate, glucose, pH) remain unclear.
Purpose of the Study:
- To investigate the sources of CSF lactate and glucose changes and the cause of brain dysfunction in experimental purulent meningitis.
Main Methods:
- Purulent meningitis was induced in rabbits using Streptococcus pneumoniae.
- CSF and brain interstitial fluid pH were measured using ion-selective microelectrodes.
- Brain cortical energy metabolites were analyzed.
Main Results:
- Infected rabbits showed meningitis symptoms, increased CSF leukocytes, lactate, and decreased glucose.
- Brain interstitial pH significantly decreased from 7.4 to 6.9.
- Brain tissue glucose levels and lactate did not differ significantly from controls, suggesting they are not the source/sink for CSF metabolites.
Conclusions:
- Purulent meningitis causes significant brain interstitial acidosis and CSF acidosis, indicating disturbed ion homeostasis.
- Activated leukocytes likely consume CSF glucose and produce lactic acid and protons, contributing to acidosis and brain dysfunction.
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