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Hypothermia decreases excitatory neurotransmitter release in bacterial meningitis in rabbits
J E Irazuzta1, J Olson, M P Kiefaber
1Division of Critical Care, Children's Hospital Medical Center, Cincinnati, OH, USA. Irazuzta@aol.com
Abstract:
The excitatory neurotransmitters glutamate (GLU) and aspartate (ASP) are involved in the pathogenesis of neuronal injury in meningitis. Based on past findings that the induction of moderate hypothermia (32-34 degrees C) attenuates the release of GLU in ischemic brain injury, this study was designed to detect if the application of moderate hypothermia decreases the release of excitatory amino acids (EAA) from brain tissue of animals with bacterial meningitis. Also examined was whether meningitis induces the expression of 72-kDa heat shock protein (HSP 70) in the cerebellum and how hypothermia affects it, for induction of HSP 70 has been used as a sensitive marker of neuronal stress in other forms of brain injury. Meningitis was induced by injecting Group B Streptococcus (GBS) into the cisterna magnae of rabbits. Antibiotic treatment began 16 h later. At this time the animals were anesthetized, instrumented, and randomized to normothermic (Nor) or hypothermic (Hy) conditions. Temperatures were strictly regimented for the following 10 h while maintaining stable cardiorespiratory parameters. Cerebrospinal fluid (CSF) samples were then withdrawn to measure concentrations of bacteria, protein, and amino acids. Meningitis causes CSF contents of GLU and ASP to increase significantly. Hypothermia treated animals demonstrated a 40-50% reduction in CSF GLU and ASP. Meningitis induced the expression of HSP 70 in the cerebellum while hypothermic animals experienced a significant decrease HSP 70 induction. These data demonstrate that hypothermia produces an attenuation of the release of excitatory neurotransmitters in meningitis and suggest that this treatment may attenuate neuronal stress.
Insights
Moderate hypothermia significantly reduced excitatory amino acids in meningitis, suggesting it may lessen neuronal stress and injury. This study explored hypothermia
Area of Science:
- Neuroscience
- Infectious Diseases
- Critical Care Medicine
Background:
- Bacterial meningitis can cause neuronal injury.
- Excitatory amino acids like glutamate (GLU) and aspartate (ASP) contribute to this injury.
- Moderate hypothermia has previously shown neuroprotective effects in ischemic brain injury.
Purpose of the Study:
- To investigate if moderate hypothermia reduces excitatory amino acid release in bacterial meningitis.
- To determine if hypothermia affects the induction of heat shock protein 70 (HSP 70) in the cerebellum during meningitis.
Main Methods:
- Bacterial meningitis was induced in rabbits using Group B Streptococcus.
- Animals received antibiotic treatment and were then randomized to normothermic or hypothermic (32-34°C) conditions for 10 hours.
- Cerebrospinal fluid (CSF) was analyzed for amino acid concentrations, and cerebellar HSP 70 expression was assessed.
Main Results:
- Meningitis significantly increased CSF GLU and ASP levels.
- Hypothermia treatment led to a 40-50% reduction in CSF GLU and ASP.
- Meningitis induced HSP 70 expression in the cerebellum, which was significantly decreased in hypothermia-treated animals.
Conclusions:
- Moderate hypothermia attenuates the release of excitatory amino acids in bacterial meningitis.
- Hypothermia reduces the induction of HSP 70, a marker of neuronal stress, during meningitis.
- These findings suggest that hypothermia may offer neuroprotection against neuronal stress in meningitis.