TY - JOUR
T1 - Dual phases of apoptosis in pneumococcal meningitis
AU - Mitchell, Lauren
AU - Smith, S. Hope
AU - Braun, Johann S.
AU - Herzog, Karl Heinz
AU - Weber, Joerg R.
AU - Tuomanen, Elaine I.
N1 - Funding Information:
Received 26 March 2004; accepted 16 June 2004; electronically published 3 November 2004. Financial support: National Institutes of Health (RO1 AI27913 to E.T.). a The last two authors contributed equally to this work. Reprints or correspondence: Dr. Elaine I. Tuomanen, Dept. of Infectious Diseases, St. Jude Children’s Research Hospital, 332 N. Lauderdale Rd., Memphis, TN 38105 (elaine.tuomanen@stjude.org).
PY - 2004/12/1
Y1 - 2004/12/1
N2 - Significant injury during bacterial meningitis arises from mechanisms of neuronal apoptosis, particularly in the hippocampus. Apoptosis can involve both the caspase-dependent and the caspase-independent pathway, and, although both pathways have been implicated in pneumococcus-induced neuronal cell death, their relative contributions in vivo are unclear. We used mice deficient in the activation of caspase-3, ATM, and p53 to examine the role that caspase-dependent apoptosis plays in neuronal death in the context of pneumococcal meningitis. The overall symptomatology of acute infection was similar in all mice tested, indicating that late sequelae are the clinical manifestations of neuronal death. Two phases of apoptosis were discernible: neuronal injury at 18 h after infection was independent of the caspase-3 pathway, and neuronal cell death at 24 h after infection was attenuated in the absence of the caspase-3 pathway. We conclude that treatments to increase the survival rate of neurons in patients with meningitis will need to take into account at least these 2 mechanisms of damage.
AB - Significant injury during bacterial meningitis arises from mechanisms of neuronal apoptosis, particularly in the hippocampus. Apoptosis can involve both the caspase-dependent and the caspase-independent pathway, and, although both pathways have been implicated in pneumococcus-induced neuronal cell death, their relative contributions in vivo are unclear. We used mice deficient in the activation of caspase-3, ATM, and p53 to examine the role that caspase-dependent apoptosis plays in neuronal death in the context of pneumococcal meningitis. The overall symptomatology of acute infection was similar in all mice tested, indicating that late sequelae are the clinical manifestations of neuronal death. Two phases of apoptosis were discernible: neuronal injury at 18 h after infection was independent of the caspase-3 pathway, and neuronal cell death at 24 h after infection was attenuated in the absence of the caspase-3 pathway. We conclude that treatments to increase the survival rate of neurons in patients with meningitis will need to take into account at least these 2 mechanisms of damage.
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U2 - 10.1086/425520
DO - 10.1086/425520
M3 - Article
C2 - 15529270
AN - SCOPUS:9444269315
SN - 0022-1899
VL - 190
SP - 2039
EP - 2046
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -