Abstract:
:Traumatic brain injury (TBI) is a leading cause of death and disability. Yet, despite immense research efforts, treatment options remain elusive. Translational failures in TBI are often attributed to the heterogeneity of the TBI population and limited methods to capture these individual variabilities. Advances in machine learning (ML) have the potential to further personalized treatment strategies and better inform translational research. However, the use of ML has yet to be widely assessed in pre-clinical neurotrauma research, where data are strictly limited in subject number. To better establish ML's feasibility, we utilized the fluid percussion injury (FPI) portion of the rich, rat data set collected by Operation Brain Trauma Therapy (OBTT), which tested multiple pharmacological treatments. Previous work has provided confidence that both unsupervised and supervised ML techniques can uncover useful insights from this OBTT pre-clinical research data set. As a proof-of-concept, we aimed to better evaluate the multi-variate recovery profiles afforded by the administration of nine different experimental therapies. We assessed supervised pairwise classifiers trained on a pre-processed data set that incorporated metrics from four feature groups to determine their ability to correctly identify specific drug treatments. In all but one of the possible pairwise combinations of minocycline, levetiracetam, erythropoietin, nicotinamide, and amantadine, the baseline was outperformed by one or more supervised classifiers, the exception being nicotinamide versus amantadine. Further, when the same methods were employed to assess different doses of the same treatment, the ML classifiers had greater difficulty in understanding which treatment each sample received. Our data serve as a critical first step toward identifying optimal treatments for specific subgroups of samples that are dependent on factors such as types and severity of traumatic injuries, as well as informing the prediction of therapeutic combinations that may lead to greater treatment effects than individual therapies.
journal_name
J Neurotraumajournal_title
Journal of neurotraumaauthors
Radabaugh H,Bonnell J,Schwartz O,Sarkar D,Dietrich WD,Bramlett HMdoi
10.1089/neu.2020.7357subject
Has Abstractpub_date
2021-01-13 00:00:00eissn
0897-7151issn
1557-9042pub_type
杂志文章abstract::Few studies have assessed the long-term functional outcomes of patients with a disorder of consciousness due to traumatic brain injury (TBI). This study examined functional status during the first 10 years after TBI among a cohort with disorders of consciousness (i.e., coma, vegetative state, minimally conscious state...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.5954
更新日期:2019-04-01 00:00:00
abstract::Death of Central Nervous System (CNS) neurons following traumatic brain injury (TBI) is a complex process arising from a combination of factors, many of which are still unknown. It has been found that inhibition of transient receptor potential (TRP) channels constitutes an effective strategy for preventing death of CN...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2012.2575
更新日期:2012-12-10 00:00:00
abstract::Neuroimaging plays an important role in assessing axonal pathology after traumatic spinal cord injury. However, coexisting inflammation confounds imaging assessment of the severity of axonal injury. Herein, we applied diffusion basis spectrum imaging (DBSI) to quantitatively differentiate and quantify underlying patho...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.6016
更新日期:2019-08-01 00:00:00
abstract::The relationship between psychotropic medication use and traumatic brain injury (TBI) is not well understood. The objective of this study was to describe patterns of psychotropic medication use during the months before and after TBI and compare with a non-TBI cohort. We conducted a retrospective cohort study using adm...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2019.6580
更新日期:2020-04-15 00:00:00
abstract::Diagnosis and early prognosis of the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and its differentiation from the minimally-conscious state still rest on the clinical observation of responsiveness. The incidence of established clinical indicators of responsiveness also has proven variable in the single...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2014.3539
更新日期:2015-07-15 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::Spinal cord injury can have a range of debilitating effects, permanently impacting a patient's quality of life. Initially thought to be an immune privileged site, the spinal cord is able to mount a timely and well organized inflammatory response to injury. Intricate immune cell interactions are triggered, typically co...
journal_title:Journal of neurotrauma
pub_type: 杂志文章,评审
doi:10.1089/neu.2014.3429
更新日期:2014-11-01 00:00:00
abstract::The aims of this study were to assess the trajectories of community integration in individuals with traumatic brain injury (TBI) through one, two, and five years post-injury and to examine whether those trajectories could be predicted by demographic and injury characteristics. A longitudinal cohort study was conducted...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2014.3844
更新日期:2016-01-01 00:00:00
abstract::We investigated the activation of lower limb motor pools by supraspinal and spinal networks after human spinal cord injury (SCI). We compared electromyographic (EMG) activity from six muscles during voluntarily attempted non-weight-bearing single-joint movements, multijoint movements approximating stepping in a supine...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/08977150260338010
更新日期:2002-10-01 00:00:00
abstract::Phosphorus 31 magnetic resonance spectroscopy (31P MRS) was used to study noninvasively the intracellular free Mg2+ concentration and cellular bioenergetic state of rat brain in vivo before and after fluid percussion-induced traumatic brain injury of graded severity. Brain injury was induced at four levels: low (1.0 +...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1988.5.315
更新日期:1988-01-01 00:00:00
abstract::Central nervous system (CNS) axons recover poorly following injury because of the expression of myelin-derived inhibitors of axonal outgrowth such as Nogo, myelin-associated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp), all of which bind to the Nogo-66 receptor 1 (NgR1). Herein we examine the rol...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2012.2493
更新日期:2013-02-15 00:00:00
abstract::This study examines the effects of combination therapy of collagen scaffolds and human marrow stromal cells (hMSCs) on the expression of tissue plasminogen activator (tPA) after traumatic brain injury (TBI) in rats. Adult male Wistar rats (n=48) were injured with controlled cortical impact and treated either with scaf...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2010.1694
更新日期:2011-07-01 00:00:00
abstract::Much recent research has focused on the pathological significance of calcium accumulation in the central nervous system (CNS) following cerebral ischemia, spinal cord injury (SCI), and traumatic brain injury (TBI). Disturbances in neuronal calcium homeostasis may result in the activation of several calcium-sensitive e...
journal_title:Journal of neurotrauma
pub_type: 杂志文章,评审
doi:10.1089/neu.1997.14.121
更新日期:1997-03-01 00:00:00
abstract::Traumatic brain injury (TBI) causes high rates of worldwide death and morbidity because of the complex secondary injury cascade. Circular ribonucleic acid (RNA) (circRNA), a type of RNA that forms a covalently closed continuous loop, may be involved in the regulation of secondary injury because it is expressed widely ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.5647
更新日期:2019-04-01 00:00:00
abstract::The aim of this systematic review was to critically evaluate the evidence on interventions for depression following traumatic brain injury (TBI) and provide recommendations for clinical practice and future research. We reviewed pharmacological, other biological, psychotherapeutic, and rehabilitation interventions for ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章,评审
doi:10.1089/neu.2009.1091
更新日期:2009-12-01 00:00:00
abstract::Delirium is a commonly reported acute care adverse event in patients with traumatic spinal cord injury (TSCI), but studies specifically investigating it in this population are lacking. The purpose of this study was to characterize the onset, risk factors, and impact of delirium in patients with TSCI. Patients discharg...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2013.2975
更新日期:2013-11-01 00:00:00
abstract::Controlled cortical impact (CCI) is a relatively new model of traumatic brain injury in the mouse, which, in combination with behavioral and histological methods, has potential for elucidating underlying mechanisms of neurodegeneration using genetically altered animals. Previously, we have demonstrated impaired spatia...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1998.15.1037
更新日期:1998-12-01 00:00:00
abstract::The serum phosphorylated neurofilament heavy subunit (pNF-H) is a nervous system-specific protein that is released from damaged neural tissue after traumatic brain injury (TBI). The aim of this study was to elucidate the usefulness of serum pNF-H as a predictive marker for the outcome of patients after TBI. Patients w...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2015.4237
更新日期:2016-10-15 00:00:00
abstract::Penetrating ballistic brain injury involves a leading shockwave producing a temporary cavity causing substantial secondary injury. In response to the prevalence of this type of brain trauma in the military, a rat model of penetrating ballistic-like brain injury (PBBI) was established. This study focuses on cerebral ph...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2010.1378
更新日期:2010-09-01 00:00:00
abstract::The role of Ca2+ in cellular injury has received particular attention in studies of acute spinal cord trauma. In this context, the spatial and temporal distribution of extracellular Ca2+ ([Ca2+]e) may have an important bearing on the development of secondary tissue injury. We therefore studied the spatial-temporal dis...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1994.11.255
更新日期:1994-06-01 00:00:00
abstract::Closed-head concussive injury is one of the most common causes of traumatic brain injury (TBI). Isolated concussions frequently produce acute neurological impairments, and individuals typically recover spontaneously within a short time frame. In contrast, brain injuries resulting from multiple concussions can result i...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2016.4679
更新日期:2017-10-01 00:00:00
abstract::Spinal cord injury caused by stab wounds (SCISW) results from a partial or complete transection of the cord, and presents opportunities for interventional research. It is recognized that there is low incidence, but little is known about the natural history or the patient's suitability for long-term clinical outcome st...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2015.4375
更新日期:2016-08-01 00:00:00
abstract::Neuroinflammation and dysfunction of the blood-brain barrier (BBB) are two prominent mechanisms of secondary injury in neurotrauma. It has been suggested that Toll-like receptors (TLRs) play important roles in initiating and propagating neuroinflammation resulting from traumatic brain injury (TBI), but potential benef...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2020.7229
更新日期:2020-10-19 00:00:00
abstract::Gap junctions are conductive channels formed by membrane proteins termed connexins (Cx), which permit the intercellular exchange of metabolites, ions, and small molecules. Junctional permeability is regulated by pH, membrane potential, and intracellular secondary messengers. The purpose of this study was to elucidate ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2009.1234
更新日期:2010-07-01 00:00:00
abstract::Traumatic brain injury (TBI) evokes diffuse (traumatic) axonal injury (TAI), which contributes to morbidity and mortality. Damaged axons display progressive alterations gradually evolving to axonal disconnection. In severe TAI, the tensile forces of injury lead to a focal influx of Ca2+, initiating a series of proteol...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/089771503321532842
更新日期:2003-03-01 00:00:00
abstract::Minimal traumatic brain injury (mTBI) is partially defined by the existence of retrograde amnesia and is associated with microscopic bleeds containing activated coagulation factors. In a previous study, we have found that mTBI immediately releases thrombin-like activity in the brain, which induces amnesia by activatin...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2015.4146
更新日期:2016-10-15 00:00:00
abstract::To assess the safety and accuracy of the Camino intraparenchymal sensor, we prospectively evaluated hemorrhagic complications, zero-drift, infection, and system malfunction in 163 patients monitored after a severe head injury. Mean duration of intracranial pressure (ICP) monitoring was 5 +/- 2.2 days (range: 12 h to 1...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/08977150252932398
更新日期:2002-04-01 00:00:00
abstract::Diffuse axonal injury (DAI) secondary to traumatic brain injury (TBI) contributes to long-term functional morbidity. The corpus callosum (CC) is particularly vulnerable to this type of injury. Magnetic resonance spectroscopy (MRS) was used to characterize the metabolic status of two CC regions of interest (ROIs) (ante...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2009.1058
更新日期:2010-03-01 00:00:00
abstract::Clinical and animal studies indicate that hyperthermia during or after traumatic brain injury (TBI) is associated with poor outcome. Alcohol intoxication, a complicating risk factor in many cases of head injury, has been found to both worsen or attenuate posttraumatic neural damage and outcome. The purpose of the pres...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/089771502762300256
更新日期:2002-12-01 00:00:00
abstract::Mild traumatic brain injury (mTBI) disrupts hippocampal function and can lead to long-lasting episodic memory impairments. The encoding of episodic memories relies on spatial information processing within the hippocampus. As the primary entry point for spatial information into the hippocampus, the dentate gyrus is tho...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2017.5350
更新日期:2018-06-01 00:00:00