Abstract:
:Traumatic brain injury (TBI) is an established risk factor for neurodegenerative disorders and dementias. Epigenetic modifications, such as DNA methylation, may alter the expression of genes without altering the DNA sequence in response to environmental factors. We hypothesized that DNA methylation changes may occur in the injured human brain and be implicated in the neurodegenerative aftermath of TBI. The DNA methylation status of genes related to neurodegeneration; for example, amyloid beta precursor protein (APP), microtubule associated protein tau (MAPT), neurofilament heavy (NEFH), neurofilament medium (NEFM), and neurofilament light (NEFL), was analyzed in fresh, surgically resected human brain tissue from 17 severe TBI patients and compared with brain biopsy samples from 19 patients with idiopathic normal pressure hydrocephalus (iNPH). We also performed an epigenome-wide association study (EWAS) comparing TBI patients with iNPH controls. Thirty-eight CpG sites in the APP, MAPT, NEFH, and NEFL genes were differentially methylated by TBI. Among the top 20 differentially methylated CpG sites, 11 were in the APP gene. In addition, the EWAS evaluating 828,888 CpG sites revealed 308 differentially methylated CpG sites in genes related to cellular/anatomical structure development, cell differentiation, and anatomical morphogenesis. These preliminary findings provide the first evidence of an altered DNA methylome in the injured human brain, and may have implications for the neurodegenerative disorders associated with TBI.
journal_name
J Neurotraumajournal_title
Journal of neurotraumaauthors
Abu Hamdeh S,Ciuculete DM,Sarkisyan D,Bakalkin G,Ingelsson M,Schiöth HB,Marklund Ndoi
10.1089/neu.2020.7283subject
Has Abstractpub_date
2021-01-08 00:00:00eissn
0897-7151issn
1557-9042pub_type
杂志文章abstract::The potential pathophysiological role of circulating microparticles (MPs) has been recognized in various conditions, such as cardiovascular and thrombotic diseases. Traumatic brain injury (TBI) has a complex pathophysiology that involves coagulopathy and inflammation. We investigated endothelial-, platelet-, and leuko...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2013.3168
更新日期:2014-12-01 00:00:00
abstract::Traumatic brain injury (TBI) has been identified as a risk factor for Alzheimer's disease (AD). However, how such neural damage contributes to AD pathology remains unclear; specifically, the relationship between the timing of a TBI relative to aging and the onset of AD pathology is not known. In this study, we have ex...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.5982
更新日期:2019-06-01 00:00:00
abstract::To examine the mechanism of the increase in cerebral blood flow induced by L-arginine administration after traumatic brain injury, the cerebral hemodynamic effects of L-arginine, D-arginine, and the free radical scavengers superoxide dismutase (SOD) and catalase were compared in the controlled cortical impact injury m...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/08977150360517209
更新日期:2003-01-01 00:00:00
abstract::Endothelial barrier antigen (EBA) is a protein triplet located in the plasma membrane of microvascular endothelium and selectively expressed in the normal nervous system. In this study, microvascular alterations following traumatic brain injury were studied using EBA immunohistochemistry. Anesthetized, physiologically...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/089771501750170958
更新日期:2001-04-01 00:00:00
abstract::The objective of this study was to determine whether clinically significant ocular trauma can be induced by a survivable isolated primary blast using a live animal model. Both eyes of 18 Dutch Belted rabbits were exposed to various survivable low-level blast overpressures in a large-scale shock tube simulating a prima...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2015.4022
更新日期:2016-07-01 00:00:00
abstract::Clinical scenario: A 37-year-old man suffered a complete spinal cord injury (C8, American Spinal Injury Association Impairment Scale [ASIA] score A) 10 years ago in a car accident. Should primary prevention of cardiovascular disease be a priority in this patient? In order to answer this question, we performed a system...
journal_title:Journal of neurotrauma
pub_type: 杂志文章,评审
doi:10.1089/neu.2012.2313
更新日期:2012-07-20 00:00:00
abstract::Stretching of cultured neurons has been used to model diffuse axonal injury associated with brain trauma. N-Methyl-D-aspartate receptor (NMDAR) activation and group I metabotropic glutamate receptors (mGluRs) are implicated in the pathophysiology of such injury. Here we detail the effects of culture condition and mGlu...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/089771503770802907
更新日期:2003-11-01 00:00:00
abstract::Sports-related concussion is a major public health problem in the United States and yet its biomechanical mechanisms remain unclear. In vitro studies demonstrate axonal elongation as a potential injury mechanism; however, current response-based injury predictors (e.g., maximum principal strain, ε(ep)) typically do not...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2013.3268
更新日期:2015-04-01 00:00:00
abstract::Mild traumatic brain injury (mTBI) contributes to development of affective disorders, including post-traumatic stress disorder (PTSD). Psychiatric symptoms typically emerge in a tardive fashion post-TBI, with negative effects on recovery. Patients with PTSD, as well as rodent models of PTSD, demonstrate structural and...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2015.4190
更新日期:2016-09-01 00:00:00
abstract::Acute subdural hematoma (ASDH) is associated with high morbidity and mortality. Whether the volume effect of the hematoma and increase of intracranial pressure (ICP) or the local effect of blood are responsible for this severe pathophysiology is unclear. Therefore, we compared subdural infusion of autologous blood and...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2016.4464
更新日期:2017-02-15 00:00:00
abstract::Transient receptor potential vanilloid 1 (TRPV1) is expressed widely in the central nervous system and is activated by various stimuli. Inhibiting TRPV1 has neuroprotective effects in cerebral ischemia. The role of inhibiting TRPV1 to maintain blood-brain barrier (BBB) integrity after traumatic brain injury (TBI) rema...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.5942
更新日期:2019-04-15 00:00:00
abstract::Paralysis is an indication for trauma patients to be preferentially triaged by emergency services to designated level I or II trauma centers (TC). We sought to describe triage practices for patients with acute traumatic spinal cord injury (TSCI) and its associated emergency department (ED) outcomes. Adults ages ≥ 18 y...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2015.4016
更新日期:2015-12-15 00:00:00
abstract::Glial cell line-derived neurotrophic factor (GDNF) has been shown to protect cranial and spinal motoneurons, which suggests potential uses of GDNF in the treatment of spinal cord injury (SCI) and motor neuron disease. We examined neuroprotective effect of cationic liposome-mediated GDNF gene transfer in vivo on axonal...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/089771502760341983
更新日期:2002-09-01 00:00:00
abstract::Clinicians are often faced with the challenging task of distinguishing between accidental and inflicted pediatric head trauma. There is currently a disparity in the anecdotal case study literature as to what kinds of injuries can occur in children from low height falls. There is also a paucity of material property dat...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2006.23.1222
更新日期:2006-08-01 00:00:00
abstract::Oxidative energy metabolism is depressed after mild/moderate traumatic brain injury (TBI) during early development, accompanied by behavioral debilitation and secondary neuronal death. A TBI metabolome analysis revealed broad effects with a striking impact on energy metabolism. Our studies on mitochondrial modulators ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.6100
更新日期:2019-04-15 00:00:00
abstract::The majority of studies do not support the use of the prophylactic anticonvulsants studied thus far for the prevention of late PTS. Routine seizure prophylaxis later than 1 week following head injury is, therefore, not recommended. If late PTS occur, patients should be managed in accordance with standard approaches to...
journal_title:Journal of neurotrauma
pub_type: 指南,杂志文章,实务指引,评审
doi:10.1089/neu.2000.17.549
更新日期:2000-06-01 00:00:00
abstract::Blast injury to the brain is one of the major causes of death and can also significantly affect cognition and physical and psychological skills in survivors of blast. The complex mechanisms via which blast injury causes impairment of cognition and other symptoms are poorly understood. In this study, we investigated th...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2010.1591
更新日期:2012-05-01 00:00:00
abstract::Concussive brain injury (CBI) accounts for approximately 75% of all brain-injured people in the United States each year and is particularly prevalent in contact sports. Concussion is the mildest form of diffuse traumatic brain injury (TBI) and results in transient cognitive dysfunction, the neuropathologic basis for w...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2010.1729
更新日期:2011-04-01 00:00:00
abstract::We evaluated in rats, the time course of changes in extracellular levels of amino acids, lactate and pyruvate, which ensued spinal cord compression of mild, moderate, and severe degrees. The neurochemical findings measured by HPLC were compared with known outcome measures of this model. A laminectomy of vertebrae Th7 ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1996.13.537
更新日期:1996-09-01 00:00:00
abstract::Spinal cord injury (SCI) is a devastating condition that affects patients on both a personal and societal level. The objective of the study is to improve the prediction of long-term functional outcome following SCI based on the acute clinical findings. A total of 76 patients with acute traumatic SCI were prospectively...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2016.4955
更新日期:2017-06-15 00:00:00
abstract::A significant outflow of neurotransmitters and metabolites with associated enhanced cortical excitation occurs after concussive head trauma. Cellular changes in the acute post-injury period cannot be observed directly in humans, and as such, require indirect evidence from systems sufficiently sensitive to central neur...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2015.3968
更新日期:2016-05-01 00:00:00
abstract::Acute changes in cerebral perfusion and metabolism after subarachnoid hemorrhage (SAH) have been shown to contribute significantly to acute brain injury. The purpose of this study was to examine the effects of moderate hypothermia on the acute changes after massive experimental SAH as evaluated by diffusion-weighted i...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2007.0443
更新日期:2008-07-01 00:00:00
abstract::Neuropathic pain and motor deficits are detrimental consequences of injury to the spinal cord. In experimental settings, numerous neuroprotective agents are being explored for their therapeutic benefits. Vascular endothelial growth factor (VEGF) is an interesting candidate molecule in this respect since it is not only...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2010.1484
更新日期:2010-10-01 00:00:00
abstract::Spinal cord injury (SCI) frequently results in chronic neuropathic pain (CNP). However, the understanding of brain neural circuits in CNP modulation is unclear. The present study examined the changes of ventral tegmental area (VTA) putative GABAergic and dopaminergic neuronal activity with CNP attenuation in rats. SCI...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2017.5381
更新日期:2018-08-01 00:00:00
abstract::Previous studies in our laboratory have shown that polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) or lidocaine treatment before experimental fluid-percussion brain injury in rats reduces the cortical hypoperfusion normally found in the early posttraumatic period. The purpose of the current study was to ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1996.13.325
更新日期:1996-06-01 00:00:00
abstract::We measured quantitative cortical mantle cerebral blood flow (CBF) by stable xenon computed tomography (CT) within the first 12 h after severe traumatic brain injury (TBI) to determine whether neurologic outcome can be predicted by CBF stratification early after injury. Stable xenon CT was used for quantitative measur...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2011.2147
更新日期:2012-03-20 00:00:00
abstract::Traumatic brain injury (TBI) results in varying degrees of disability in a significant number of persons annually. The mechanisms of cognitive dysfunction after TBI have been explored in both animal models and human clinical studies for decades. Dopaminergic, serotonergic, and noradrenergic dysfunction has been descri...
journal_title:Journal of neurotrauma
pub_type: 杂志文章,评审
doi:10.1089/neu.2014.3445
更新日期:2015-10-01 00:00:00
abstract::Aging may be an important factor affecting brain injury by intracerebral hemorrhage (ICH). In the present study, we investigated the responses of glial cells and monocytes to intracerebral hemorrhage in normal and aged rats. ICH was induced by microinjecting autologous whole blood (15 microL) into the striatum of youn...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2008.0630
更新日期:2009-09-01 00:00:00
abstract::Lesions in specific areas of the rat motor cortex generate deficits related to fine movement performance affecting the forelimb. We have previously shown that transplants of embryonic frontal cortex ameliorate these motor deficits. Amelioration has been associated with a functional integration of the transplant due to...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2008.0702
更新日期:2009-09-01 00:00:00
abstract::In various animal and human studies, early administration of 17β-estradiol, a strong antioxidant, anti-inflammatory, and anti-apoptotic agent, significantly decreases the severity of injury in the brain associated with cell death. Estrone, the predominant estrogen in postmenopausal women, has been shown to be a promis...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2011.2274
更新日期:2012-08-10 00:00:00