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

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.

2021 ◽  
Vol 12 ◽  
Author(s):  
Savannah Anne Daines

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.


2013 ◽  
Vol 21 (2) ◽  
pp. 222-228
Author(s):  
Daniel Garbin Di Luca ◽  
Glenda Corrêa Borges de Lacerda

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.


Author(s):  
Mary Beth Howard ◽  
Nichole McCollum ◽  
Emily C. Alberto ◽  
Hannah Kotler ◽  
Mary E. Mottla ◽  
...  

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.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Marc Fakhoury ◽  
Zaynab Shakkour ◽  
Firas Kobeissy ◽  
Nada Lawand

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.


2021 ◽  
Vol 11 (6) ◽  
pp. 806
Author(s):  
Thorsten Rudroff ◽  
Craig D. Workman

Mild traumatic brain injury (mTBI) has been defined as a transient (<24 h) condition of confusion and/or loss of consciousness for less than 30 min after brain injury and can result in short- and long-term motor and cognitive impairments. Recent studies have documented the therapeutic potential of non-invasive neuromodulation techniques for the enhancement of cognitive and motor function in mTBI. Alongside repetitive transcranial magnetic stimulation (rTMS), the main technique used for this purpose is transcranial direct current stimulation (tDCS). The focus of this review was to provide a detailed, comprehensive (i.e., both cognitive and motor impairment) overview of the literature regarding therapeutic tDCS paradigms after mTBI. A publication search of the PubMed, Scopus, CINAHL, and PsycINFO databases was performed to identify records that applied tDCS in mTBI. The publication search yielded 14,422 records from all of the databases, however, only three met the inclusion criteria and were included in the final review. Based on the review, there is limited evidence of tDCS improving cognitive and motor performance. Surprisingly, there were only three studies that used tDCS in mTBI, which highlights an urgent need for more research to provide additional insights into ideal therapeutic brain targets and optimized stimulation parameters.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Catherine D. Chong ◽  
Jianwei Zhang ◽  
Jing Li ◽  
Teresa Wu ◽  
Gina Dumkrieger ◽  
...  

Abstract Background/objective Changes in speech can be detected objectively before and during migraine attacks. The goal of this study was to interrogate whether speech changes can be detected in subjects with post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) and whether there are within-subject changes in speech during headaches compared to the headache-free state. Methods Using a series of speech elicitation tasks uploaded via a mobile application, PTH subjects and healthy controls (HC) provided speech samples once every 3 days, over a period of 12 weeks. The following speech parameters were assessed: vowel space area, vowel articulation precision, consonant articulation precision, average pitch, pitch variance, speaking rate and pause rate. Speech samples of subjects with PTH were compared to HC. To assess speech changes associated with PTH, speech samples of subjects during headache were compared to speech samples when subjects were headache-free. All analyses were conducted using a mixed-effect model design. Results Longitudinal speech samples were collected from nineteen subjects with PTH (mean age = 42.5, SD = 13.7) who were an average of 14 days (SD = 32.2) from their mTBI at the time of enrollment and thirty-one HC (mean age = 38.7, SD = 12.5). Regardless of headache presence or absence, PTH subjects had longer pause rates and reductions in vowel and consonant articulation precision relative to HC. On days when speech was collected during a headache, there were longer pause rates, slower sentence speaking rates and less precise consonant articulation compared to the speech production of HC. During headache, PTH subjects had slower speaking rates yet more precise vowel articulation compared to when they were headache-free. Conclusions Compared to HC, subjects with acute PTH demonstrate altered speech as measured by objective features of speech production. For individuals with PTH, speech production may have been more effortful resulting in slower speaking rates and more precise vowel articulation during headache vs. when they were headache-free, suggesting that speech alterations were related to PTH and not solely due to the underlying mTBI.


Sign in / Sign up

Export Citation Format

Share Document