Neurofilament medium polypeptide (NFM) protein concentration is increased in CSF and serum samples from patients with brain injury

Abstract

Brain injury is a medical emergency that needs to be diagnosed and treated promptly. Several proteins have been studied as biomarkers of this medical condition. The aims of this study were to: 1) evaluate the selectivity and precision of a commercial ELISA kit for neurofilament medium polypeptide (NFM) protein; and 2) evaluate the concentration in cerebrospinal fluid (CSF) and serum of healthy individuals and patients with brain damage.An ELISA from Elabscience was used. The selectivity was evaluated using size-exclusion chromatography and mass spectrometry. Intra- and inter-batch coefficients of variation (CV) were also studied. Fifty-one CSF samples from 36 age-matched patients with hemorrhagic stroke (HS) (n=30), ischemic stroke (IS) (n=11) and healthy individuals (n=10) were assayed. In addition, serum samples from healthy volunteers (n=47), 68 serum samples from seven patients with HS, 106 serum samples from 12 patients with traumatic brain injury (TBI) and 68 serum samples from 68 patients with mild traumatic brain injury (mTBI) were also analyzed.NFM was identified in the chromatographic fraction with highest immunoreactivity. The intra- and inter-batch CVs were ≤10% and ≤13%, respectively. The CSF-NFM concentration in HS was significantly higher (p<0.0001) than in IS and controls. Serum NFM concentration ranged from 0.26 to 8.57 ng/mL in healthy individuals (median=2.29), from 0.97 to 42.4 ng/mL in HS (median=10.8) and from 3.48 to 45.4 ng/mL in TBI (median=14.7). Finally, 44% of patients with mTBI had increased NFM concentration, with significantly higher levels (p=0.01) in patients with polytrauma.To our knowledge this is the first study describing increased NFM levels in CSF and serum from patients with brain damage.

Serum neurofilament light protein predicts clinical outcome in traumatic brain injury

“…However, large myelinated axons, which are enriched in neurofilament are believed to be more vulnerable to traumatic brain injury8, suggesting that neurofilament measured in blood may have better both diagnostic and prognostic utility than tau for acute TBI. Previous studies have attempted to quantify NF-M, and NF-H in patients with stroke and TBI using traditional ELISA, where only less than 50% of patients with TBI had increased serum NF-M with significantly higher levels in polytrauma patients, thus casting doubt on the utility of NF-M as a specific biomarker for TBI1314. However, of the three subunits of neurofilament, NF-L is the most abundant and essential component of the neurofilament core, acting as the backbone to which NF-M and NF-H co-assemblies1516.…”

P3‐193: Serum Neurofilament Light Protein Predicts Clinical Outcome in Traumatic Brain Injury

“…However, large myelinated axons, which are enriched in neurofilament are believed to be more vulnerable to traumatic brain injury 8 , suggesting that neurofilament measured in blood may have better both diagnostic and prognostic utility than tau for acute TBI. Previous studies have attempted to quantify NF-M, and NF-H in patients with stroke and TBI using traditional ELISA, where only less than 50% of patients with TBI had increased serum NF-M with significantly higher levels in polytrauma patients, thus casting doubt on the utility of NF-M as a specific biomarker for TBI 13,14 . However, of the three subunits of neurofilament, NF-L is the most abundant and essential component of the neurofilament core, acting as the backbone to which NF-M and NF-H co-assemblies 15,16 .…”

How to Translate Time: The Temporal Aspects of Rodent and Human Pathobiological Processes in Traumatic Brain Injury

“…Injury increased levels of these proteins in the blood (and CSF) have shown correlation with the onset and extent of axonal injury both experimentally and clinically enabling improved comparisons between clinical and experimental data. [104][105][106][107][108] Injury-induced disintegration of the axoskeleton is mediated by calcium-dependent enzymes calpain and caspase-3. These enzymes are activated by the sudden rise in intracellular calcium levels and the activated enzymes then breaking down spectrin.…”