Plasminogen activator inhibitor-1 influences cerebrovascular complications and death in pneumococcal meningitis

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ID: 118224
2013
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Abstract
Cerebrovascular complications are common in pneumococcal meningitis and are a main determinant of unfavourable outcome and death. We hypothesized that plasminogen activator inhibitor-1 (PAI-1) is a major contributor to cerebrovascular complications and death in pneumococcal meningitis. In a nationwide prospective cohort study we evaluated the effect of the 4G/5G polymorphism (rs1799889) in SERPINE1 (coding for PAI-1) on cerebrovascular complications and outcome in adults with pneumococcal meningitis proven by cerebrospinal fluid (CSF) culture. From 2006 to 2011, a total of 991 adult patients with community-acquired bacterial meningitis were included in the cohort and 712 had pneumococcal meningitis. The rs1799889 5G/5G genotype was associated with an increased risk of unfavourable outcome [odds ratio (OR) 1.69, 95 % confidence interval (CI) 1.03–2.78] and mortality (OR 2.20, 95 % CI 1.02–4.86) in white adults with pneumococcal meningitis. rs1799889 was associated with CSF PAI-1 concentrations (P = 0.048), and white patients homozygous for the low PAI-1 producing genotype (5G/5G) had a significantly higher risk for cerebral infarctions (P = 0.015) and haemorrhages (P = 0.005). Subsequently, we assessed the functionality of PAI-1 in a pneumococcal meningitis mouse model, using Serpine1 knockout mice. Consistent with the human data, Serpine1-deficient mice had increased mortality and cerebral haemorrhages compared to wild-type mice. We conclude PAI-1 is protective for death in humans and mice with pneumococcal meningitis by reducing cerebrovascular complications.
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Authors Matthijs C. Brouwer;Joost C. M. Meijers;Frank Baas;Arie van der Ende;Hans-Walter Pfister;Armin Giese;Diederik van de Beek;Uwe Koedel;Matthijs C. Brouwer;Joost C. M. Meijers;Frank Baas;Arie van der Ende;Hans-Walter Pfister;Armin Giese;Diederik van de Beek;Uwe Koedel;
Journal acta neuropathologica
Year 2013
DOI
doi:10.1007/s00401-013-1216-4
URL
https://link.springer.com/article/10.1007/s00401-013-1216-4
Keywords
pathology neurosciences

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