Nevertheless, this brain region would, by its neurogenic potential, be well equipped for repair and increased neuronal proliferation is indeed observed shortly after bacterial meningitis, but it is neither sufficient nor sustainable. The Morris water maze evaluates predominantly spatial memory and hippocampal apoptosis is associated with decreased learning performance in this task. We therefore hypothesized that lithium prevents hippocampal apoptosis in acute experimental PM by down-regulating expression of pro-apoptotic genes, while up-regulating anti-apoptotic genes. Further into the investigation of its effects in PM, LiCl was applied in a clinically relevant setting, i.e. after infection,Rhodojaponin-III to evaluate its impact on the neurofunctional outcome. We hypothesized that lithium supports neuronal regeneration by increasing proliferation and survival of neuronal stem/progenitor cells in the damaged hippocampus eventually improving neurofunctional outcome. Thus, we evaluated the survival of new-born cells in the DG during three weeks following PM while the animals were treated with LiCl. Based on its neuroprotective and neuro regenerative properties, this is the first study evaluating lithium as a potential therapeutic strategy in the context of bacterial meningitis. During probe trials, the platform was removed. Mean distance to the center of the previous location of the platform, number of platform crossings and time spent in the platform’s quadrant were measured. LiCl treatment significantly improved learning performance measured by these three parameters at the end of the learning process, Rhodojaponin-II on day 5. Differences between the treatment groups did not reach statistical significance on days 1 to 4. The effect of lithium treatment was stronger than the effect of infection in the variations between groups reaching statistical significance in the 2way ANOVA on day 5. To evaluate the effects of lithium treatment it was necessary to find a valid treatment regimen. In the infant rat model of PM, 57 mmol/l LiCl was most effective to reach desired lithium serum and CSF concentrations during pre-treatment, eventually preventing hippocampal brain damage. However, a slightly reduced weight gain in LiCl treated animals was observed during pretreatment, which could be explained by polyuria, a known adverse effect of lithium.