Effects of Toll-like receptor 2 agonist Pam3CysSK4 on inflammation and brain damage in experimental pneumococcal meningitis

TLR2 signaling participates in the pathogenesis of pneumococcal meningitis. In infant rats, the TLR2 agonist Pam3CysSK4 was applied intracisternally (0.5 μg in 10 μl 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 Pam3CysSK4 on apoptosis was investigated by intracisternal application of 0.5 μg in 10 μl saline and 40 μg in 20 μl saline. Pam3CysSK4 neither induced apoptosis in sham-operated mice nor aggravated apoptosis in acute infection. However, Pam3CysSK4 induced pleocytosis, TNF-α and MMP-9 in CSF in sham-infection but not during acute meningitis. We conclude that TLR2 signaling triggered by Pam3CysSK4 at a dosage capable to induce a neuroinflammatory response does not induce hippocampal apoptosis in the infant rat model of experimental pneumococcal meningitis.