Short CommunicationThe effect of systemic inflammation on human brain barrier function

- Systemic inflammation impairs blood-brain barrier (BBB) in preclinical models.
- In humans, BBB function was assessed by the CSF/serum albumin ratio (CSAR).
- Systemic inflammation did not affect CSAR in the non-inflamed brain.
- Systemic inflammation increased CSAR in the presence of brain inflammation.
- The diseased BBB has an increased susceptibility to systemic inflammation.

The blood-brain barrier (BBB) plays an important role in the clinical expression of neuropsychiatric symptoms during systemic illness in health and neurological disease. Evidence from in vitro and preclinical in vivo studies indicate that systemic inflammation impairs blood-brain barrier function. In order to investigate this hypothesis, we evaluated the association between systemic inflammatory markers (leucocytes, erythrocyte sedimentation rate and C-reactive protein) and BBB function (cerebrospinal fluid/serum albumin ratio) in 1273 consecutive lumbar punctures. In the absence of cerebrospinal fluid (CSF) abnormality, systemic inflammation did not affect the CSF/serum albumin ratio. When CSF abnormality was present, systemic inflammation significantly predicted the CSF/serum albumin ratio. Amongst the systemic inflammatory markers, C-reactive protein was the predominant driver of this effect. Temporal analysis in this association study suggested causality. In conclusion, the diseased BBB has an increased susceptibility to systemic inflammation.