Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway / 国际口腔科学杂志·英文版

Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer's disease (AD). The blood-brain barrier (BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1 (Cav-1) expression was enhanced after P. gingivalis infection. Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain (RgpA) were detected. Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a (Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.

Clinical profile of Group A meningococcal outbreak in Delhi.

We present a retrospective analysis of clinical profile of 100 children admitted to a Government hospital at Delhi between April 2005 and December 2006 with group A meningococcal infection. Maximum children presented in late winter and spring.Younger children were less affected (5% children < 1 year). Fever (86%), vomiting (64%) and rash (63%) were the most common presenting symptoms. All children presented within 5 days of onset of symptoms and 52% within 24 hours. 67 % children had meningococcal meningitis; 20% had meningococcemia; and 13% had both. Overall mortality was 17%. Altered sensorium and shock at presentation significantly increased the mortality. All culture positive cases had group A Neisseria meningitides. All meningococcal isolates were sensitive to penicillin/ampicillin, ciprofloxacin, ceftriaxone, chloramphenicol and erythromycin except, one each resistant to ampicillin and erythromycin.