scholarly journals The Therapeutic Potential and Limitations of Ketones in Traumatic Brain Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Savannah Anne Daines
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Therapeutic Potential ◽  
Experimental Models ◽  
Neurological Deficits ◽  
Optimal Timing ◽  
Health Crisis ◽  
Metabolic Monitoring ◽  
Post Traumatic ◽  
Significant Health

Traumatic brain injury (TBI) represents a significant health crisis. To date, no FDA approved pharmacotherapies are available to prevent the neurological deficits caused by TBI. As an alternative to pharmacotherapy treatment of TBI, ketones could be used as a metabolically based therapeutic strategy. Ketones can help combat post-traumatic cerebral energy deficits while also reducing inflammation, oxidative stress, and neurodegeneration. Experimental models of TBI suggest that administering ketones to TBI patients may provide significant benefits to improve recovery. However, studies evaluating the effectiveness of ketones in human TBI are limited. Unanswered questions remain about age- and sex-dependent factors, the optimal timing and duration of ketone supplementation, and the optimal levels of circulating and cerebral ketones. Further research and improvements in metabolic monitoring technology are also needed to determine if ketone supplementation can improve TBI recovery outcomes in humans.

scholarly journals Antagonism of Macrophage Migration Inhibitory Factory (MIF) after Traumatic Brain Injury Ameliorates Astrocytosis and Peripheral Lymphocyte Activation and Expansion

2020 ◽  
Vol 21 (20) ◽  
pp. 7448
Author(s):  
M. Karen Newell-Rogers ◽  
Susannah K. Rogers ◽  
Richard P. Tobin ◽  
Sanjib Mukherjee ◽  
Lee A. Shapiro
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
B Cells ◽  
Therapeutic Potential ◽  
Lymphocyte Activation ◽  
Clinical Problem ◽  
Causative Role ◽  
Macrophage Migration ◽  
Γδt Cells ◽  
Post Traumatic

Traumatic brain injury (TBI) precedes the onset of epilepsy in up to 15–20% of symptomatic epilepsies and up to 5% of all epilepsy. Treatment of acquired epilepsies, including post-traumatic epilepsy (PTE), presents clinical challenges, including frequent resistance to anti-epileptic therapies. Considering that over 1.6 million Americans present with a TBI each year, PTE is an urgent clinical problem. Neuroinflammation is thought to play a major causative role in many of the post-traumatic syndromes, including PTE. Increasing evidence suggests that neuroinflammation facilitates and potentially contributes to seizure induction and propagation. The inflammatory cytokine, macrophage migration inhibitory factor (MIF), is elevated after TBI and higher levels of MIF correlate with worse post-traumatic outcomes. MIF was recently demonstrated to directly alter the firing dynamics of CA1 pyramidal neurons in the hippocampus, a structure critically involved in many types of seizures. We hypothesized that antagonizing MIF after TBI would be anti-inflammatory, anti-neuroinflammatory and neuroprotective. The results show that administering the MIF antagonist ISO1 at 30 min after TBI prevented astrocytosis but was not neuroprotective in the peri-lesion cortex. The results also show that ISO1 inhibited the TBI-induced increase in γδT cells in the gut, and the percent of B cells infiltrating into the brain. The ISO1 treatment also increased this population of B cells in the spleen. These findings are discussed with an eye towards their therapeutic potential for post-traumatic syndromes, including PTE.

scholarly journals Approaches to Monitor Circuit Disruption after Traumatic Brain Injury: Frontiers in Preclinical Research

2020 ◽  
Vol 21 (2) ◽  
pp. 588 ◽  
Author(s):  
Gokul Krishna ◽  
Joshua A. Beitchman ◽  
Caitlin E. Bromberg ◽  
Theresa Currier Thomas
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Experimental Models ◽  
Neurological Deficits ◽  
Preclinical Research ◽  
Behavioral Deficits ◽  
Efferent Connections ◽  
And Function ◽  
Circuit Function

Mild traumatic brain injury (TBI) often results in pathophysiological damage that can manifest as both acute and chronic neurological deficits. In an attempt to repair and reconnect disrupted circuits to compensate for loss of afferent and efferent connections, maladaptive circuitry is created and contributes to neurological deficits, including post-concussive symptoms. The TBI-induced pathology physically and metabolically changes the structure and function of neurons associated with behaviorally relevant circuit function. Complex neurological processing is governed, in part, by circuitry mediated by primary and modulatory neurotransmitter systems, where signaling is disrupted acutely and chronically after injury, and therefore serves as a primary target for treatment. Monitoring of neurotransmitter signaling in experimental models with technology empowered with improved temporal and spatial resolution is capable of recording in vivo extracellular neurotransmitter signaling in behaviorally relevant circuits. Here, we review preclinical evidence in TBI literature that implicates the role of neurotransmitter changes mediating circuit function that contributes to neurological deficits in the post-acute and chronic phases and methods developed for in vivo neurochemical monitoring. Coupling TBI models demonstrating chronic behavioral deficits with in vivo technologies capable of real-time monitoring of neurotransmitters provides an innovative approach to directly quantify and characterize neurotransmitter signaling as a universal consequence of TBI and the direct influence of pharmacological approaches on both behavior and signaling.

scholarly journals Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury

2019 ◽  
Vol 20 (3) ◽  
pp. 502 ◽  
Author(s):  
Buyandelger Batsaikhan ◽  
Jing-Ya Wang ◽  
Michael Scerba ◽  
David Tweedie ◽  
Nigel Greig ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Neuronal Degeneration ◽  
Neurological Deficits ◽  
Post Injury ◽  
Neuroprotective Effects ◽  
Tnf Α

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Long-term deficits after TBI arise not only from the direct effects of the injury but also from ongoing processes such as neuronal excitotoxicity, inflammation, oxidative stress and apoptosis. Tumor necrosis factor-α (TNF-α) is known to contribute to these processes. We have previously shown that 3,6′-dithiothalidomide (3,6′-DT), a thalidomide analog that is more potent than thalidomide with similar brain penetration, selectively inhibits the synthesis of TNF-α in cultured cells and reverses behavioral impairments induced by mild TBI in mice. In the present study, we further explored the therapeutic potential of 3,6′-DT in an animal model of moderate TBI using Sprague-Dawley rats subjected to controlled cortical impact. A single dose of 3,6′-DT (28 mg/kg, i.p.) at 5 h after TBI significantly reduced contusion volume, neuronal degeneration, neuronal apoptosis and neurological deficits at 24 h post-injury. Expression of pro-inflammatory cytokines in the contusion regions were also suppressed at the transcription and translation level by 3,6′-DT. Notably, neuronal oxidative stress was also suppressed by 3,6′-DT. We conclude that 3,6′-DT may represent a potential therapy to ameliorate TBI-induced functional deficits.

Time Interval Between Traumatic Brain Injury And Post Traumatic Epilepsy

2013 ◽  
Vol 21 (2) ◽  
pp. 222-228
Author(s):  
Daniel Garbin Di Luca ◽  
Glenda Corrêa Borges de Lacerda
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
First Year ◽  
Time Interval ◽  
Partial Seizures ◽  
Complex Partial Seizures ◽  
Post Traumatic ◽  
Faster Development ◽  
Post Traumatic Epilepsy ◽  
Traumatic Epilepsy

Introduction. The estimated time interval in which an individual can develop Post Traumatic Epilepsy (PTE) after a traumatic brain injury (TBI) is not clear. Objective. To assess the possible influence of the clinical features in the time interval between TBI and PTE develop­ment. Method. We analyzed retrospectively 400 medical records from a tertiary Brazilian hospital. We selected and reevaluated 50 patients and data was confronted with the time between TBI and PTE devel­opment by a Kaplan-Meier survival analysis. A Cox-hazard regression was also conducted to define the characteristics that could be involved in the latent period of the PTE development. Results. Patients devel­oped PTE especially in the first year (56%). We found a tendency of a faster development of PTE in patients older than 24 years (P<0.0001) and in men (P=0.03). Complex partial seizures evolving to generalized seizures were predominant in patients after moderate (37.7%) and severe (48.8%) TBIs, and simple partial seizures evolving to general­ized seizures in mild TBIs (45.5%). Conclusions. Our data suggest that the first year after a TBI is the most critical period for PTE de­velopment and those males older than 24 years could have a faster development of PTE.

Association of Ventilation during Initial Trauma Resuscitation for Traumatic Brain Injury and Post-Traumatic Outcomes: A Systematic Review

2021 ◽  
pp. 1-6
Author(s):  
Mary Beth Howard ◽  
Nichole McCollum ◽  
Emily C. Alberto ◽  
Hannah Kotler ◽  
Mary E. Mottla ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Systematic Review ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Trauma Resuscitation ◽  
Cerebral Herniation ◽  
Full Text Review ◽  
Post Traumatic ◽  
Ventilation Strategies ◽  
End Tidal

Abstract Objectives: In the absence of evidence of acute cerebral herniation, normal ventilation is recommended for patients with traumatic brain injury (TBI). Despite this recommendation, ventilation strategies vary during the initial management of patients with TBI and may impact outcome. The goal of this systematic review was to define the best evidence-based practice of ventilation management during the initial resuscitation period. Methods: A literature search of PubMed, CINAHL, and SCOPUS identified studies from 2009 through 2019 addressing the effects of ventilation during the initial post-trauma resuscitation on patient outcomes. Results: The initial search yielded 899 articles, from which 13 were relevant and selected for full-text review. Six of the 13 articles met the inclusion criteria, all of which reported on patients with TBI. Either end-tidal carbon dioxide (ETCO2) or partial pressure carbon dioxide (PCO2) were the independent variables associated with mortality. Decreased rates of mortality were reported in patients with normal PCO2 or ETCO2. Conclusions: Normoventilation, as measured by ETCO2 or PCO2, is associated with decreased mortality in patients with TBI. Preventing hyperventilation or hypoventilation in patients with TBI during the early resuscitation phase could improve outcome after TBI.

scholarly journals Depression following traumatic brain injury: a comprehensive overview

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Marc Fakhoury ◽  
Zaynab Shakkour ◽  
Firas Kobeissy ◽  
Nada Lawand
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Health Concern ◽  
First Year ◽  
Comprehensive Overview ◽  
Symptoms Of Depression ◽  
Current State ◽  
Post Traumatic ◽  
Brain Changes

Abstract Traumatic brain injury (TBI) represents a major health concern affecting the neuropsychological health; TBI is accompanied by drastic long-term adverse complications that can influence many aspects of the life of affected individuals. A substantial number of studies have shown that mood disorders, particularly depression, are the most frequent complications encountered in individuals with TBI. Post-traumatic depression (P-TD) is present in approximately 30% of individuals with TBI, with the majority of individuals experiencing symptoms of depression during the first year following head injury. To date, the mechanisms of P-TD are far from being fully understood, and effective treatments that completely halt this condition are still lacking. The aim of this review is to outline the current state of knowledge on the prevalence and risk factors of P-TD, to discuss the accompanying brain changes at the anatomical, molecular and functional levels, and to discuss current approaches used for the treatment of P-TD.

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