Serum Neurofilament Light as a Biomarker of Traumatic Brain Injury in the Presence of Concomitant Peripheral Injury

Wong, Ker Rui; O’Brien, William T.; Sun, Mujun; Yamakawa, Glenn R.; O’Brien, Terence J.; Mychasiuk, Richelle; Shultz, Sandy R.; McDonald, Stuart J.; Brady, Rhys D.

doi:10.1177/11772719211053449

Cited by 11 publications

(33 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animal models of TBI enable detailed longitudinal studies on the temporal expression of potential plasma molecular biomarkers and how their levels relate to disease severity and progression [ 10 ]. Several studies have assessed circulating NF-L levels in rodent TBI models, including those induced by lateral FPI, single or repeated mild awake closed-head injury, and Marmarou’s weight-drop injury in rats [ 23 , 24 , 25 , 26 ], and a closed-head impact model of engineered rotational acceleration (CHIMERA) in mice [ 27 ]. All but one of these reports, however, focused on mild or mild-to-moderate TBI [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have assessed circulating NF-L levels in rodent TBI models, including those induced by lateral FPI, single or repeated mild awake closed-head injury, and Marmarou’s weight-drop injury in rats [ 23 , 24 , 25 , 26 ], and a closed-head impact model of engineered rotational acceleration (CHIMERA) in mice [ 27 ]. All but one of these reports, however, focused on mild or mild-to-moderate TBI [ 25 ]. To the best of our knowledge, the present study is the first to assess circulating NF-L concentrations over time and their value as a preclinical prognostic biomarker for chronic functional outcomes after severe TBI induced by lateral FPI.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI

Heiskanen

Jääskeläinen

Manninen

et al. 2022

IJMS

View full text Add to dashboard Cite

Plasma neurofilament light chain (NF-L) levels were assessed as a diagnostic biomarker for traumatic brain injury (TBI) and as a prognostic biomarker for somatomotor recovery, cognitive decline, and epileptogenesis. Rats with severe TBI induced by lateral fluid-percussion injury (n = 26, 13 with and 13 without epilepsy) or sham-operation (n = 8) were studied. During a 6-month follow-up, rats underwent magnetic resonance imaging (MRI) (day (D) 2, D7, and D21), composite neuroscore (D2, D6, and D14), Morris-water maze (D35–D39), and a 1-month-long video-electroencephalogram to detect unprovoked seizures during the 6th month. Plasma NF-L levels were assessed using a single-molecule assay at baseline (i.e., naïve animals) and on D2, D9, and D178 after TBI or a sham operation. Plasma NF-L levels were 483-fold higher on D2 (5072.0 ± 2007.0 pg/mL), 89-fold higher on D9 (930.3 ± 306.4 pg/mL), and 3-fold higher on D176 32.2 ± 8.9 pg/mL after TBI compared with baseline (10.5 ± 2.6 pg/mL; all p < 0.001). Plasma NF-L levels distinguished TBI rats from naïve animals at all time-points examined (area under the curve [AUC] 1.0, p < 0.001), and from sham-operated controls on D2 (AUC 1.0, p < 0.001). Plasma NF-L increases on D2 were associated with somatomotor impairment severity (ρ = −0.480, p < 0.05) and the cortical lesion extent in MRI (ρ = 0.401, p < 0.05). Plasma NF-L increases on D2 or D9 were associated with the cortical lesion extent in histologic sections at 6 months post-injury (ρ = 0.437 for D2; ρ = 0.393 for D9, p < 0.05). Plasma NF-L levels, however, did not predict somatomotor recovery, cognitive decline, or epileptogenesis (p > 0.05). Plasma NF-L levels represent a promising noninvasive translational diagnostic biomarker for acute TBI and a prognostic biomarker for post-injury somatomotor impairment and long-term structural brain damage.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI

Heiskanen

Jääskeläinen

Manninen

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Furthermore, many of these proteins have been observed with elevated levels following injuries that are not TBIs, raising concerns about the specificity of individual markers and prompting the use of biomarker panels. 143 …”

Section: Proteomic Biomarkersmentioning

confidence: 99%

Progress Toward a Multiomic Understanding of Traumatic Brain Injury: A Review

et al. 2022

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is not a single disease state but describes an array of conditions associated with insult or injury to the brain. While some individuals with TBI recover within a few days or months, others present with persistent symptoms that can cause disability, neuropsychological trauma, and even death. Understanding, diagnosing, and treating TBI is extremely complex for many reasons, including the variable biomechanics of head impact, differences in severity and location of injury, and individual patient characteristics. Because of these confounding factors, the development of reliable diagnostics and targeted treatments for brain injury remains elusive. We argue that the development of effective diagnostic and therapeutic strategies for TBI requires a deep understanding of human neurophysiology at the molecular level and that the framework of multiomics may provide some effective solutions for the diagnosis and treatment of this challenging condition. To this end, we present here a comprehensive review of TBI biomarker candidates from across the multiomic disciplines and compare them with known signatures associated with other neuropsychological conditions, including Alzheimer’s disease and Parkinson’s disease. We believe that this integrated view will facilitate a deeper understanding of the pathophysiology of TBI and its potential links to other neurological diseases.

show abstract

“…Hyperactivity of microglial and astrocytic removal of amyloid-β from cerebrospinal fluid (Bagnato et al, 2018;Wong et al, 2021).…”

Section: Cellular Mechanismsmentioning

confidence: 99%

“…Specifically, it is hypothesized that, after DOC inducing brain injury, microglia show increased: phagocytotic activity, contacts with neurons ("satellite microglia"), secretion of pro-inflammatory cytokines, and synaptic pruning (Ramlackhansingh et al, 2011;Donat et al, 2017;Krukowski et al, 2021). As outlined by Bagnato et al (2021), increased NFL levels may additionally result from a loss of BBB integrity and altered amyloid-β levels, evidence for which have been observed after traumatic brain injury in rats (Mannix and Whalen, 2012;van Vliet et al, 2020;Wong et al, 2021) and in patients with DOCs (Bagnato et al, 2017(Bagnato et al, , 2018. Microglia and astrocytes also play critical roles in maintaining BBB integrity and amyloid-β levels, further implicating these cells in the observed DOC related NFL concentrations (Rogers et al, 2002;Mannix and Whalen, 2012;Ries and Sastre, 2016;Haruwaka et al, 2019;Heithoff et al, 2021).…”

Section: Structural Connectivitymentioning

confidence: 99%

The implication of a diversity of non-neuronal cells in disorders affecting brain networks

Carrier

Dolhan²,

Bobotis³

et al. 2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

In the central nervous system (CNS) neurons are classically considered the functional unit of the brain. Analysis of the physical connections and co-activation of neurons, referred to as structural and functional connectivity, respectively, is a metric used to understand their interplay at a higher level. A myriad of glial cell types throughout the brain composed of microglia, astrocytes and oligodendrocytes are key players in the maintenance and regulation of neuronal network dynamics. Microglia are the central immune cells of the CNS, able to affect neuronal populations in number and connectivity, allowing for maturation and plasticity of the CNS. Microglia and astrocytes are part of the neurovascular unit, and together they are essential to protect and supply nutrients to the CNS. Oligodendrocytes are known for their canonical role in axonal myelination, but also contribute, with microglia and astrocytes, to CNS energy metabolism. Glial cells can achieve this variety of roles because of their heterogeneous populations comprised of different states. The neuroglial relationship can be compromised in various manners in case of pathologies affecting development and plasticity of the CNS, but also consciousness and mood. This review covers structural and functional connectivity alterations in schizophrenia, major depressive disorder, and disorder of consciousness, as well as their correlation with vascular connectivity. These networks are further explored at the cellular scale by integrating the role of glial cell diversity across the CNS to explain how these networks are affected in pathology.

show abstract

Serum Neurofilament Light as a Biomarker of Traumatic Brain Injury in the Presence of Concomitant Peripheral Injury

Cited by 11 publications

References 27 publications

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI

Progress Toward a Multiomic Understanding of Traumatic Brain Injury: A Review

The implication of a diversity of non-neuronal cells in disorders affecting brain networks

Contact Info

Product

Resources

About