The Latest Articles on Traumatic Brain Injury (TBI)
Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles on Traumatic Brain Injury (TBI).
Title: Changes in the cardiac autonomic control system during rehabilitation in children after severe traumatic brain injury
Authors: Gilad Sorek, Isabelle Gagnon, Kathryn Schneider, Mathilde Chevignard, Nurit Stern, Yahaloma Fadida, Liran Kalderon, Sharon Shaklai, Michal Katz-Leurer
Type: Research Article
Abstract:
Background
One of the sequalae of severe traumatic brain injury (TBI) in children is impaired function of the cardiac autonomic control system (CACS) at rest. The CACS response to conventional autonomic tests is little known.
Objective
To examine the CACS response to conventional autonomic tests in children after severe TBI during the rehabilitation period and to compare with typically developing (TD) children.
Methods
This study combined a case-control and follow-up design. The severe TBI group (cases) consisted of 33 children aged 9–18 years, 14–142 days after severe TBI who were followed for 8 weeks during rehabilitation. The control group consisted of 19 TD children matched for age and sex. Heart rate (HR) and heart rate variability (HRV) were evaluated with the Polar RS800CX device at rest (sitting), during a handgrip test and during a paced breathing test.
Results
At the first assessment, we found lower HRV values at rest and a lower HRV response during the paced breathing and handgrip tests in the TBI group than the TD group (p < 0.01). After 8 weeks, HRV values did not change at rest in the TBI group, but the response to the autonomic tests improved significantly, with increased HRV values in response to the paced breathing test (p < 0.01) and the handgrip test (p = 0.01).
Conclusions
After severe TBI, children exhibited an impaired CACS response to autonomic tests, with parasympathetic suppression and sympathetic arousal. After 8 weeks of rehabilitation, CACS function recovered partially and the response to the autonomic tests improved with no change in CACS function at rest.
Access this article: https://doi.org/10.1016/j.rehab.2022.101652
Title: TrkB agonist N-acetyl serotonin promotes functional recovery after traumatic brain injury by suppressing ferroptosis via the PI3K/Akt/Nrf2/Ferritin H pathway
Authors: Ying Cheng, Yuan Gao, Jing Li, Tongyu Rui, Qianqian Li, Huan Chen, Bowen Jia, Yiting Song, Zhiya Gu, Tao Wang, Cheng Gao, Ying Wang, Zufeng Wang, Fudi Wang, Luyang Tao, Chengliang Luo
Type: Research Article
Abstract:
Ferroptosis is a form of regulated cell death that is mainly triggered by iron-dependent lipid peroxidation. A growing body of evidence suggests that ferroptosis is involved in the pathophysiology of traumatic brain injury (TBI), and tropomyosin-related kinase B (TrkB) deficiency would mediate TBI pathologies. As an agonist of TrkB and an immediate precursor of melatonin, N-acetyl serotonin (NAS) exerts several beneficial effects on TBI, but there is no information regarding the role of NAS in ferroptosis after TBI. Here, we examined the effect of NAS treatment on TBI-induced functional outcomes and ferroptosis. Remarkably, the administration of NAS alleviated TBI-induced neurobehavioral deficits, lesion volume, and neurodegeneration. NAS also rescued TBI-induced mitochondrial shrinkage, the changes in ferroptosis-related molecule expression, and iron accumulation in the ipsilateral cortex. Similar results were obtained with a well-established ferroptosis inhibitor, liproxstatin-1. Furthermore, NAS activated the TrkB/PI3K/Akt/Nrf2 pathway in the mouse model of TBI, while inhibition of PI3K and Nrf2 weakened the protection of NAS against ferroptosis both in vitro and in vivo, suggesting that a possible pathway linking NAS to the action of anti-ferroptosis was TrkB/PI3K/Akt/Nrf2. Given that ferritin H (Fth) is a known transcription target of Nrf2, we then investigated the effects of NAS on neuron-specific Fth knockout (Fth-KO) mice. Strikingly, Fth deletion almost abolished the protective effects of NAS against TBI-induced ferroptosis and synaptic damage, although Fth deletion-induced susceptibility toward ferroptosis after TBI was reversed by an iron chelator, deferoxamine. Taken together, these data indicate that the TrkB agonist NAS treatment appears to improve brain function after TBI by suppressing ferroptosis, at least in part, through activation of the PI3K/Akt/Nrf2/Fth pathway, providing evidence that NAS is likely to be a promising anti-ferroptosis agent for further treatment for TBI.
Access this article: https://doi.org/10.1016/j.freeradbiomed.2022.12.002
Title: A comparison of diffusion tensor imaging tractography and constrained spherical deconvolution with automatic segmentation in traumatic brain injury
Authors: Jussi Tallus, Mehrbod Mohammadian, Timo Kurki, Timo Roine, Jussi P. Posti, Olli Tenovuo
Type: Research Article
Abstract:
Detection of microstructural white matter injury in traumatic brain injury (TBI) requires specialised imaging methods, of which diffusion tensor imaging (DTI) has been extensively studied. Newer fibre alignment estimation methods, such as constrained spherical deconvolution (CSD), are better than DTI in resolving crossing fibres that are ubiquitous in the brain and may improve the ability to detect microstructural injuries. Furthermore, automatic tract segmentation has the potential to improve tractography reliability and accelerate workflow compared to the manual segmentation commonly used. In this study, we compared the results of deterministic DTI based tractography and manual tract segmentation with CSD based probabilistic tractography and automatic tract segmentation using TractSeg. 37 participants with a history of TBI (with Glasgow Coma Scale 13–15) and persistent symptoms, and 41 healthy controls underwent deterministic DTI-based tractography with manual tract segmentation and probabilistic CSD-based tractography with TractSeg automatic segmentation.Fractional anisotropy (FA) and mean diffusivity of corpus callosum and three bilateral association tracts were measured. FA and MD values derived from both tractography methods were generally moderately to strongly correlated. CSD with TractSeg differentiated the groups based on FA, while DTI did not. CSD and TractSeg-based tractography may be more sensitive in detecting microstructural changes associated with TBI than deterministic DTI tractography. Additionally, CSD with TractSeg was found to be applicable at lower b-value and number of diffusion-encoding gradients data than previously reported.
Access this article: https://doi.org/10.1016/j.nicl.2022.103284
Title: A decade of blood-brain barrier permeability assays: Revisiting old traumatic brain injury rat data for new insights and experimental design
Authors: Chris T. Bolden, Scott D. Olson, Charles S. Cox Jr
Type: Research Article
Abstract:
Increased microvascular permeability at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema following traumatic brain injury (TBI). These pathologic conditions compromise the integrity of the neurovascular unit resulting in severe brain dysfunction. To quantify this permeability and assess ionic equillibrium, preclinical researchers have relied on the use of various molecular weight permeable dyes such as Evans Blue that normally cannot enter the brain parenchyma under homeostatic conditions. Evans Blue, the most cited of the molecular weight dyes, has reported reproducibility issues because of harsh extraction processes, suboptimal detection via absorbance, and wide excitation fluorescence spectra associated with the dye. Our laboratory group transitioned to Alexa Fluor 680, a far-red dye with improved sensitivity compared to Evans Blue and thus improved reproducibility to alleviate this issue. To evaluate our reproducibility and increase the rigor of our experimental design, we retrospectively analyzed our controlled cortical impact (CCI) experiments over the past 10 years to evaluate effect size with larger samples and potential sources of variability. All of our BBB permeability experiments were performed with Male, Sprague Dawley rats weighing between 225 and 300 g. Historically, Sprague Dawleys were randomly divided into treatment groups: SHAM, CCI, and a stem cell-based treatment from years 2007–2020. The assessment of microvascular hyperpermeability were evaluated by comparing the mean at minimum threshold, area at 1 k–2 k, and intensity density obtained from Alexa Fluor 680 permeability data. Studies utilizing Evans Blue were further compared by tip depth, diameter size, and the hemisphere of injury. Statistical evaluation utilizing the G Power software analysis did not yield a significant difference in sample size comparing experimental groups for Evans Blue and Alexa Fluor 680 analyzed brain tissue. Our analysis also demonstrated a trend in that recent studies (years 2018–2020) have yielded more compact sample sizes between experimental groups in Alexa Fluor 680 analyzed rats. This retrospective study further revealed that Alexa Fluor 680 image analysis provides greater sensitivity to BBB permeability following TBI in comparison to Evans Blue. Significant differences in sample size were not detected between Evans Blue and Alexa Fluor 680; there were significant differences found throughout year to year analysis at the lower range of thresholds.
Access this article: https://doi.org/10.1016/j.mvr.2022.104453
Title: Wide-field calcium imaging reveals widespread changes in cortical functional connectivity following mild traumatic brain injury in the mouse
Authors: Samuel W. Cramer, Samuel P. Haley, Laurentiu S. Popa, Russell E. Carter, Earl Scott, Evelyn B. Flaherty, Judith Dominguez, Justin D. Aronson, Luke Sabal, Daniel Surinach, Clark C. Chen, Suhasa B. Kodandaramaiah, Timothy J. Ebner
Type: Research Article
Abstract:
> 2.5 million individuals in the United States suffer mild traumatic brain injuries (mTBI) annually. Mild TBI is characterized by a brief period of altered consciousness, without objective findings of anatomic injury on clinical imaging or physical deficit on examination. Nevertheless, a subset of mTBI patients experience persistent subjective symptoms and repeated mTBI can lead to quantifiable neurological deficits, suggesting that each mTBI alters neurophysiology in a deleterious manner not detected using current clinical methods. To better understand these effects, we performed mesoscopic Ca2+ imaging in mice to evaluate how mTBI alters patterns of neuronal interactions across the dorsal cerebral cortex. Spatial Independent Component Analysis (sICA) and Localized semi-Nonnegative Matrix Factorization (LocaNMF) were used to quantify changes in cerebral functional connectivity (FC). Repetitive, mild, controlled cortical impacts induce temporary neuroinflammatory responses, characterized by increased density of microglia exhibiting de-ramified morphology. These temporary neuro-inflammatory changes were not associated with compromised cognitive performance in the Barnes maze or motor function as assessed by rotarod. However, long-term alterations in functional connectivity (FC) were observed. Widespread, bilateral changes in FC occurred immediately following impact and persisted for up to 7 weeks, the duration of the experiment. Network alterations include decreases in global efficiency, clustering coefficient, and nodal strength, thereby disrupting functional interactions and information flow throughout the dorsal cerebral cortex. A subnetwork analysis shows the largest disruptions in FC were concentrated near the impact site. Therefore, mTBI induces a transient neuroinflammation, without alterations in cognitive or motor behavior, and a reorganized cortical network evidenced by the widespread, chronic alterations in cortical FC.
Access this article: https://doi.org/10.1016/j.nbd.2022.105943
