Hypothermia decreases excitatory neurotransmitter release in bacterial meningitis in rabbits.
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 Cerebrospinal fluid (CSF) samples were then withdrawn to measure concentrations of bacteria, protein, and amino acids.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.
Irazuzta
J E
JE
Division of Critical Care, Children's Hospital Medical Center, Cincinnati, OH, USA. Irazuzta@aol.com
Olson
J
J
Kiefaber
M P
MP
Wong
H
H
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D018846:Excitatory Amino Acids / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D016920:Meningitis, Bacterial / Q000503:physiopathology* / Q000628:therapy*; D011817:Rabbits
D018846:Excitatory Amino Acids; D018840:HSP70 Heat-Shock Proteins; D001224:Aspartic Acid; D018698:Glutamic Acid