The role of minocycline in cognitive impairment and dysfunction of the blood brain barrier in experimental pneumococcal meningitis

Abstract

Bacterial meningitis is a life threatening infection associated with cognitive impairment in many survivors. The pathogen invades the CNS by penetrating through the luminal side of the cerebral endothelium, which is an integral part of the BBB. Microglia are the resident macrophages of the CNS which can trigger a host of immunological pathways. The inflammatory response from microglial activation can facilitate the elimination of invasive microorganisms; however, excessive or extended microglial activation can result in neuronal damage and eventually cell death. The inhibition of microglia using minocycline can be a relevant pharmacological tool to study the role of microglia in different CNS diseases. In this study, animals received either artificial cerebrospinal fluid or a Streptococcus pneumoniae suspension. The animals receive minocycline or saline immediately after induction. For the evaluation of the BBB integrity, the animals were killed at 12, 18 and 24 h after induction. For the behavioural tests, ten days after meningitis was induced, were subjected to open-field habituation and the step-down inhibitory task. In both cerebral structures the use of the minocycline prevented BBB disruption. In the behavioural tests the use of minocycline prevented habituation and aversive memory impairment in the meningitis/minocycline group when compared with meningitis/saline. Our results demonstrate that the minocycline was able to decrease long-term cognitive impairment and BBB dysfunction in rats survivors of meningitis representing a new pharmacological approach towards pneumococcal meningitis.