PMID- 34210150
OWN - NLM
STAT- MEDLINE
DCOM- 20220217
LR  - 20240229
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Linking)
VI  - 38
IP  - 20
DP  - 2021 Oct 15
TI  - Phosphorylated Neurofilament Heavy Chain in the Cerebrospinal Fluid Is a Suitable 
      Biomarker of Acute and Chronic Blast-Induced Traumatic Brain Injury.
PG  - 2801-2810
LID - 10.1089/neu.2021.0144 [doi]
AB  - Blast-induced traumatic brain injury (bTBI) has been documented as a significant 
      concern for both military and civilian populations in response to the increased 
      use of improvised explosive devices. Identifying biomarkers that could aid in the 
      proper diagnosis and assessment of both acute and chronic bTBI is in urgent need 
      since little progress has been made towards this goal. Addressing this knowledge 
      gap is especially important in military veterans who are receiving assessment and 
      care often years after their last blast exposure. Neuron-specific phosphorylated 
      neurofilament heavy chain protein (pNFH) has been successfully evaluated as a 
      reliable biomarker of different neurological disorders, as well as brain trauma 
      resulting from contact sports and acute stages of brain injury of different 
      origin. In the present study, we have evaluated the utility of pNFH levels 
      measured in the cerebrospinal fluid (CSF) as an acute and chronic biomarker of 
      brain injury resulting from single and tightly coupled repeated blast exposures 
      using experimental rats. The pNFH levels increased at 24 h, returned to normal 
      levels at 1 month, but increased again at 6 months and 1 year post-blast 
      exposures. No significant changes were observed between single and repeated 
      blast-exposed groups. To determine whether the observed increase of pNFH in CSF 
      corresponded with its levels in the brain, we performed fluorescence 
      immunohistochemistry in different brain regions at the four time-points 
      evaluated. We observed decreased pNFH levels in those brain areas at 24 h, 6 
      months, and 1 year. The results suggest that blast exposure causes axonal 
      degeneration at acute and chronic stages resulting in the release of pNFH, the 
      abundant neuronal cytoskeletal protein. Moreover, the changes in pNFH levels in 
      the CSF negatively correlated with the neurobehavioral functions in the rats, 
      reinforcing suggestions that CSF levels of pNFH can be a suitable biomarker of 
      bTBI.
FAU - Arun, Peethambaran
AU  - Arun P
AD  - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland, 
      USA.
FAU - Rossetti, Franco
AU  - Rossetti F
AD  - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland, 
      USA.
FAU - Eken, Ondine
AU  - Eken O
AD  - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland, 
      USA.
FAU - Wilder, Donna M
AU  - Wilder DM
AD  - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland, 
      USA.
FAU - Wang, Ying
AU  - Wang Y
AD  - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland, 
      USA.
FAU - Long, Joseph B
AU  - Long JB
AD  - Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and 
      Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210721
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Biomarkers)
RN  - 0 (Neurofilament Proteins)
SB  - IM
MH  - Animals
MH  - Biomarkers/cerebrospinal fluid
MH  - Blast Injuries/*cerebrospinal fluid/pathology
MH  - Brain/pathology
MH  - Brain Injuries, Traumatic/*cerebrospinal fluid/pathology
MH  - Disease Models, Animal
MH  - Immunohistochemistry
MH  - Male
MH  - Neurofilament Proteins/*cerebrospinal fluid
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Treatment Outcome
OTO - NOTNLM
OT  - biomarker
OT  - blast exposure
OT  - cerebrospinal fluid
OT  - neurodegeneration
OT  - phosphorylated neurofilament heavy chain
OT  - traumatic brain injury
EDAT- 2021/07/03 06:00
MHDA- 2022/02/19 06:00
CRDT- 2021/07/02 05:30
PHST- 2021/07/03 06:00 [pubmed]
PHST- 2022/02/19 06:00 [medline]
PHST- 2021/07/02 05:30 [entrez]
AID - 10.1089/neu.2021.0144 [doi]
PST - ppublish
SO  - J Neurotrauma. 2021 Oct 15;38(20):2801-2810. doi: 10.1089/neu.2021.0144. Epub 
      2021 Jul 21.