The effect of systemic inflammation on human brain barrier function.
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.
Clinical Neurosciences, Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Elliot
E
Elwood
Clinical Neurosciences, Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Zhi
Z
Lim
Clinical Neurosciences, Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Hammad
H
Naveed
Clinical Neurosciences, Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. Electronic address: I.Galea@soton.ac.uk.
Ian
I
Galea
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001799:Blood Sedimentation; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012709:Serum Albumin / Q000378:metabolism
D015415:Biomarkers; D012709:Serum Albumin; D002097:C-Reactive Protein
Albumin; Blood-brain barrier; Cerebrospinal fluid; Infection; Inflammation; Systemic