title: Axonal pathology in subarachnoid and intracerebral hemorrhage.
abstract: Electrically active axons degenerate in the presence of nitric oxide (NO) in vitro. High CSF NO concentrations have been observed in patients with hemorrhagic brain injury such as subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). This study investigated the evidence for axonal injury in SAH and ICH and related this to CSF NO levels. In this study, neurofilament phosphoforms (NfH(SMI34), NfH(SMI35), NfH(SMI38), NfH(SMI310)), surrogate markers for axonal injury, and NO metabolites (nitrate, nitrite = NOx) were measured by ELISA in cerebrospinal fluid (CSF) from patients with SAH and ICH and from a group of controls. Injury severity was classified using the Glasgow Coma Scale, and survival was used as the outcome measure. Compared to the control group, a higher proportion of patients with SAH and ICH had elevated NfH(SMI34) levels from day 0 to day 6 (p < 0.001), elevated NfH(SMI35) levels from day 1 to 6 (p < 0.001), and elevated NfH(SMI310) levels at day 0, 1, 4, and 6 (p < 0.001). The NOx levels were higher in the SAH and ICH patients than in the controls (p < 0.05) and distinguished the non-survivors from the survivors (p < 0.05). No direct correlation was found for NOx with any of the NfH phosphoforms. This study provides evidence for primary and secondary axonal injury in patients with SAH and ICH, with non-survivors also having higher NOx levels. CSF NfH phosphoforms might emerge as a putative surrogate marker for monitoring the development for secondary axonal degeneration in neurocritical care and guiding targeted neuroprotective strategies.
authors.affiliation: Department of Neuroimmunology, Institute of Neurology, University College London, London, United Kingdom. a.petzold@ion.ucl.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Petzold
authors.forename: K
authors.initials: K
authors.lastname: Rejdak
authors.forename: A
authors.initials: A
authors.lastname: Belli
authors.forename: J
authors.initials: J
authors.lastname: Sen
authors.forename: G
authors.initials: G
authors.lastname: Keir
authors.forename: N
authors.initials: N
authors.lastname: Kitchen
authors.forename: M
authors.initials: M
authors.lastname: Smith
authors.forename: E J
authors.initials: EJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D001369:Axons / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000134:cerebrospinal fluid* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D009569:Nitric Oxide / Q000134:cerebrospinal fluid; D011446:Prospective Studies; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000473:pathology*
chemical_list: D016900:Neurofilament Proteins; D009569:Nitric Oxide