title: Non-neurological surgery and cerebrospinal fluid biomarkers for neuronal and astroglial integrity.
abstract: Non-neurological surgery has both acute and long-term effects on the brain. Markers for Alzheimer pathology may be used to study surgically induced neurological changes relevant for postoperative confusion, asthenia or cognitive decline. Inflammatory biomarkers, total tau (T-tau) and phosphorylated tau (P-tau) were recently shown to increase progressively in the cerebrospinal fluid (CSF) during surgery for nasal CSF leak, suggesting a neuroinflammatory response with signs of neuronal damage. We used a study group of 35 patients, undergoing knee arthroplasty with a spinal blockade and propofol sedation, to replicate this finding. Five CSF biomarkers were analyzed before, 3 h after and on the morning after the interventions: T-tau and P-tau for cortical axonal integrity and tangle pathology, respectively, the 42 amino acids form of amyloid β (Aβ42) for plaque formation, neurofilament light (NFL) for the integrity of large-caliber myelinated axons and glial fibrillary acidic protein (GFAp) for astroglial cell integrity. CSF T-tau concentrations increased significantly during and after surgery (p = 0.028) and were significantly correlated with the administered doses of bupivacaine. P-tau, Aβ42 and NFL remained unchanged, while the mean GFAp concentration increased with a large standard deviation. CSF T-tau and P-tau correlated significantly with the CSF/serum albumin ratios as an indicator of blood-brain barrier permeability. Findings from earlier studies showing a significant increase in biomarkers for Alzheimer's pathology during surgery were partly replicated, as neurochemical signs of impaired cortical axonal integrity during non-neurological surgery were detected. Bupivacaine may be involved in these reactions.
authors.affiliation: Department of Anaesthesiology and Intensive Care, Anestesikliniken, Kungälv Hospital, 442 83, Kungälv, Sweden, rolf.anckarsater@neuro.gu.se.
authors.forename: Rolf
authors.initials: R
authors.lastname: Anckarsäter
authors.forename: Henrik
authors.initials: H
authors.lastname: Anckarsäter
authors.forename: Sara
authors.initials: S
authors.lastname: Bromander
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Caroline
authors.initials: C
authors.lastname: Wass
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000601:surgery; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000704:Analysis of Variance; D019645:Arthroplasty, Replacement, Knee / Q000379:methods*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D007718:Knee Injuries / Q000134:cerebrospinal fluid / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D015742:Propofol / Q000627:therapeutic use; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D006993:Hypnotics and Sedatives; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D015742:Propofol