Exp Ther Med. 2017 Mar;13(3):799-809. doi: 10.3892/etm.2017.4082. Epub 2017 Jan 24.

Role of neural barriers in the pathogenesis and outcome of Streptococcus pneumoniae meningitis.

Prager O1,2, Friedman A1,2,3, Nebenzahl YM4.

Author information

Abstract

Bacterial meningitis is an inflammatory disease of the meninges of the central nervous system (CNS). Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis, and Haemophilus influenzae are the major bacterial pathogens causing meningitis with S. pneumoniae being responsible for two thirds of meningitis cases in the developed world. To reach the CNS following nasopharyngeal colonization and bacteraemia, the bacteria traverse from the circulation across the blood brain barrier (BBB) and choroid plexus. While the BBB has a protective role in healthy individuals by shielding the CNS from neurotoxic substances circulating in the blood and maintaining the homeostasis within the brain environment, dysfunction of the BBB is associated with the pathophysiology of numerous neurologic disorders, including bacterial meningitis. Inflammatory processes, including release of a broad range of cytokines and free radicals, further increase vascular permeability and contribute to the excessive neural damage observed. Injury to the cerebral microvasculature and loss of blood flow auto-regulation promote increased intracranial pressure and may lead to vascular occlusion. Other common complications commonly associated with meningitis include abnormal neuronal hyper-excitability (e.g., seizures) and loss of hearing. Despite the existence of antibiotic treatment and adjuvant therapy, the relatively high mortality rate and the severe outcomes among survivors of pneumococcal meningitis in developing and developed countries increase the urgency in the requirement of discovering novel biomarkers for the early diagnosis as well as novel treatment approaches. The present review aimed to explore the changes in the brain vascular barriers, which allow S. pneumoniae to invade the CNS, and describe the resultant brain injuries following bacterial meningitis.

KEYWORDS:

S. pneumoniae; blood brain barrier; central nervous system; inflammation; innate immunity; meningitis; pathogenesis; virulence factors

PMID: 28450902 PMCID: PMC5403536 DOI: 10.3892/etm.2017.4082