Effects of Toll-like receptor 2 agonist Pam(3)CysSK(4) on inflammation and brain damage in experimental pneumococcal meningitis.
TLR2 signaling participates in the pathogenesis of pneumococcal meningitis. In infant rats, the TLR2 agonist Pam(3)CysSK(4) was applied intracisternally (0.5 microg in 10 microl saline) alone or after induction of pneumococcal meningitis to investigate the effect of TLR2 activation on cerebrospinal fluid (CSF) inflammation and hippocampal apoptosis. A dose effect of Pam(3)CysSK(4) on apoptosis was investigated by intracisternal application of 0.5 microg in 10 microl saline and 40 microg in 20 microl saline. Pam(3)CysSK(4) neither induced apoptosis in sham-operated mice nor aggravated apoptosis in acute infection. However, Pam(3)CysSK(4) induced pleocytosis, TNF-alpha and MMP-9 in CSF in sham-infection but not during acute meningitis. We conclude that TLR2 signaling triggered by Pam(3)CysSK(4) at a dosage capable to induce a neuroinflammatory response does not induce hippocampal apoptosis in the infant rat model of experimental pneumococcal meningitis.
Sellner
Johann
J
Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str.22, D-81675 München, Germany.
Grandgirard
Denis
D
Gianinazzi
Christian
C
Landmann
Regine M
RM
Leib
Stephen L
SL
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D007249:Inflammation / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000209:etiology*; D007962:Leukocytes / Q000187:drug effects; D055666:Lipopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000150:complications* / Q000401:mortality / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9