Brain-Derived Neurotrophic Factor Rescues Neurons From Bacterial Meningitis

The responsiveness of TrkB to exogenous BDNF in frontal cortex during antibiotic treatment of Streptococcus pneumoniae meningitis

“…Our previous studies found that BDNF and its receptor TrkB mRNA decreased in the neurons of cortex and hippocampus suffering from S. pneumoniae meningitis when treated by antibiotics [12,13], and adjuvant administration of exogenous BDNF could increase the number of survived neurons in cortex and hippocampus and improve the hearing function of these animals, however, the control animals had serious hearing disfunction 7 days after administration of antibiotics plus placebo [14,17]. In the present study, the expression of TrkB mRNA in the neurons of frontal cortex after adjuvant therapy of placebo in S. pneumoniae meningitis was much lower than normal level, and this phenomenon could be persistent, which further confirmed that endogenous neuroprotection was weakened by decreased TrkB expression, and TrkB expression might be regulated by intrinsic BDNF, because the decrease of BDNF expression were persistent in bacterial meningitis after treatment with antibiotics [12,13,18].…”

“…These findings suggested that TrkB and intrinsic BDNF decreased concomitantly in S. pneumoniae meningitis after treatment with antibiotics. We then found that adjuvant administration of exogenous BDNF could rescue neurons from S. pneumoniae meningitis [14]. We speculated that exogenous BDNF administration might play a neuroprotective role by regulating the expression of TrkB receptor in S. pneumoniae meningitis.…”

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

“…Moreover, rats inoculated with group B streptococci demonstrated less cognitive decline following adjunctive treatment with the pan-caspase inhibitor bocaspartyl (OMe)-fluoromethylketone (210). An interesting observation is that exogenous administration of brain-derived neutrotrophic factor (BDNF), which has been shown to block caspase-3 (191), reduced neuronal apoptosis in both rat and murine models (44,293). BDNF was found to be upregulated naturally during bacterial meningitis and after treatment with antibiotics with adjunctive dexamethasone yet lowered during standard antibiotic treatment, suggesting a possible mechanism of corticosteroid therapy (294).…”

Sodium Butyrate Prevents Memory Impairment by Re-establishing BDNF and GDNF Expression in Experimental Pneumococcal Meningitis

“…Previously, we demonstrated that animals surviving pneumococcal meningitis presented learning and memory impairments [4,5] and that there was a correlation between a decrease in brain-derived neurotropic factor (BDNF) expression in the hippocampus and memory deficiency [6]. The administration of exogenous BDNF had neuroprotective effects on both the cerebral cortex and hippocampus, increasing the neuronal population and re-establishing normal BDNF and tyrosine-related kinase B (TRKB) levels, which had decreased in the brain during experimental pneumococcal meningitis [7]. BDNF has been shown to be involved in the differentiation and survival of neurons in the CNS, and it is implicated in a variety of neural and molecular events that are important to cognition, learning and memory [8,9].…”