scholarly journals Cerebrovascular and neurological impact of chronic smoking on post traumatic brain injury outcome and recovery: an in vivo study

2019 ◽  
Author(s):  
Farzane Sivandzade ◽  
Faleh Alqahtani ◽  
Ali Sifat ◽  
Luca Cucullo
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Vascular Inflammation ◽  
Post Injury ◽  
Transcript Factor ◽  
Weight Drop ◽  
Post Traumatic ◽  
Chronic Smoking ◽  
Age Range

Abstract Background: Traumatic Brain Injury (TBI) is among the most prevalent causes of cerebrovascular and neurological damage worldwide. To this end, tobacco smoking (TS) has been shown to promote vascular inflammation, neurovascular impairments and risk of cerebrovascular and neurological disorders through oxidative stress (OS) stimuli targeting the blood-brain barrier (BBB) endothelium among others. It has been recently suggested that premorbid conditions such as TS may exacerbate post-TBI brain damage and impact recovery. The present study aims to investigate and dissect out the pathophysiological mechanisms underlying the exacerbation of TBI in a weight-drop model following chronic TS exposure. Methods: C57BL/6J male mice, age range 6–8 weeks were chronically exposed to TS for three weeks. Test animals were then subjected to TBI by guided vertical head weight drop using a 30 g metal weight free felling from an 80 cm distance before reaching the target. Physical activity and body weight of the mice were analyzed before TBI and 1 h, 24 h and 3 days post-injury. Finally, mice were sacrificed to collect blood and brain samples for subsequent biochemical and molecular analysis. Western blotting was applied to assess the expression of Nrf2 (a key antioxidant transcription factor) as well as tight junction proteins associated with BBB integrity including, ZO-1, Occludin, Claudin-5 from brain tissues homogenates. Levels of NF-kB (a pro-inflammatory transcript factor which antagonizes Nrf2 activity) along with pro-inflammatory cytokines IL-6, IL-10 and TNF-α were measured by ELISA on blood samples. Results: TS promoted significantly increased inflammation and loss of BBB integrity in TBI when compared to TS-Free test mice. Additionally, mice chronically exposed to TS prior to TBI experienced a more significant weight loss, behavioral, and motor activity deficiency and slower post-TBI recovery when compared to TS-free TBI mice. Conclusion: TS promotes a significant exacerbation of post-TBI neurovascular and neurological impairments. Whereas BBB impairment and pro-inflammatory vascular responses induced by chronic TS exposure are likely responsible for the retardation of post-traumatic recovery observed in these animals.

scholarly journals 513 Understanding the Role of HMGB1 Post-Traumatic Brain Injury - The Complex Interplay Between Neuro-Inflammation and Neurogenesis

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
O Marei ◽  
S Manivannan ◽  
O Elalfy ◽  
M Zaben
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Current Evidence ◽  
Post Injury ◽  
Term Survival ◽  
Positive Effects ◽  
Pubmed Database ◽  
Post Traumatic

Abstract Introduction Traumatic brain injury (TBI) is a global public health burden. Although neurogenesis occurs post-injury, achieving long term survival of newly generated neurons remains elusive. High Mobility Group Box protein 1 (HMGB1) is a pivotal cytokine in hosting the neuro-inflammatory response to injury, but also mediates neurogenesis during physiological development. In this review, we examine current evidence for post-traumatic neurogenesis and HMGB1 as a therapeutic target. Method PubMed database was evaluated with the following search terms: HMGB1, isoforms, neurogenesis, traumatic brain injury, Toll-like receptor, receptor for advanced glycation end-products. Results Multiple studies support the existence of neurogenesis post-injury both in vitro and in vivo. Different HMGB1 target receptors mediate different functions of HMGB1, though these are not mutually exclusive in the context of injury. Interaction with RAGE is responsible for developmental neurogenesis, whilst TLR-4 mediates the innate immune response. Though different HMGB1 isoforms are recognised, specific effects post-injury remains unexplored. In vivo animal studies demonstrate positive effects of HMGB1 antagonism post-TBI, but long-term outcomes remain unclear. Conclusions Modulating HMGB1 may enhance post-TBI recovery, but a mechanistic understanding of its effects on neurogenesis is fundamental to avoid negating potentially beneficial effects.

scholarly journals Traumatic Brain Injury as a Disorder of Brain Connectivity

2016 ◽  
Vol 22 (2) ◽  
pp. 120-137 ◽  
Author(s):  
Jasmeet P. Hayes ◽  
Erin D. Bigler ◽  
Mieke Verfaellie
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Functional Connectivity ◽  
Negative Impact ◽  
Axonal Injury ◽  
Resting State Functional Connectivity ◽  
Post Injury ◽  
Recent Advances

AbstractObjectives:Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition.Methods:We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury.Results:The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes.Conclusions:TBI has a negative impact on distributed brain networks that lead to behavioral disturbance. (JINS, 2016,22, 120–137)

scholarly journals A pilot study exploring pupil response measurement in mild traumatic brain injury

2015 ◽  
Vol 42 (S1) ◽  
pp. S40-S40
Author(s):  
W Ting ◽  
J Topolovec-Vranic ◽  
M McGowan ◽  
MD Cusimano
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Healthy Controls ◽  
Response Dynamics ◽  
Post Injury ◽  
Response Measurement ◽  
Pupil Response ◽  
Post Traumatic ◽  
Traumatic Symptoms

Background: Pupillometry, the measurement of pupil response dynamics via the pupillary light reflex, is seldom used in the assessment of mild traumatic brain injury (mTBI). We hypothesized that there would be quantifiable differences in detailed pupil response measurements in patients with acute and chronic mTBI. Methods: We conducted 49 bilateral pupillometry measurements, in acute mTBI patients at 1-week (N=11), 2-4w (N=9), and 3-7mo post-injury (N=3); 14 patients with persistent post-traumatic symptoms (PTS) once, and healthy controls across a first visit (N=7) and second visit 2-4w later (N=5). Results: The percentage of left pupil diameter change was significantly greater in the acute mTBI group at second visit (mean=36.3% (2.96)), compared to controls at second visit (mean=31.6% (4.39)) (F=5.87, p=0.0321). We did not identify significant differences between acute mTBI patients and controls at first visit, PTS patients versus controls, and within the acute mTBI group across three longitudinal visits. Conclusion: While these preliminary data suggest that pupillometry under these conditions does not distinguish between patients who had a recent mTBI or those with PTS and healthy controls, further research is warranted investigating pupil behavior and its clinical utility in mTBI.

scholarly journals Seizures are a druggable mechanistic link between TBI and subsequent tauopathy

2020 ◽  
Author(s):  
Hadeel Alyenbaawi ◽  
Richard Kanyo ◽  
Laszlo F. Locskai ◽  
Razieh Kamali-Jamil ◽  
Michèle G. DuVal ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cell Death ◽  
Brain Injury ◽  
Chronic Traumatic Encephalopathy ◽  
Brain Activity ◽  
Brain Regions ◽  
List Type ◽  
Larval Zebrafish ◽  
Post Traumatic

SummaryTraumatic brain injury (TBI) is a prominent risk factor for neurodegenerative diseases and dementias including chronic traumatic encephalopathy (CTE). TBI and CTE, like all tauopathies, are characterized by accumulation of Tau into aggregates that progressively spread to other brain regions in a prion-like manner. The mechanisms that promote spreading and cellular uptake of tau seeds after TBI are not fully understood, in part due to lack of tractable animal models. Here, we test the putative roles for excess neuronal activity and dynamin-dependent endocytosis in promoting the in vivo spread of tauopathy. We introduce ‘tauopathy reporter’ zebrafish expressing a genetically-encoded fluorescent Tau biosensor that reliably reports accumulation of human tau species when seeded via intra-ventricular brain injections. Subjecting zebrafish larvae to a novel TBI paradigm produced various TBI symptoms including cell death, hemorrhage, blood flow abnormalities, post–traumatic seizures, and Tau inclusions. Bath application of anticonvulsant drugs rescued TBI-induced tauopathy and cell death; these benefits were attributable to inhibition of post-traumatic seizures because co-application of convulsants reversed these beneficial effects. However, one convulsant drug, 4-Aminopyridine, unexpectedly abrogated TBI-induced tauopathy - this was due to its inhibitory action on endocytosis as confirmed via additional dynamin inhibitors. These data suggest a role for seizure activity and dynamin-dependent endocytosis in the prion-like seeding and spreading of tauopathy following TBI. Further work is warranted regarding anti-convulsants that dampen post-traumatic seizures as a route to moderating subsequent tauopathy. Moreover, the data highlight the utility of deploying in vivo Tau biosensor and TBI methods in larval zebrafish, especially regarding drug screening and intervention.Graphical AbstractHighlightsIntroduces first Traumatic Brain Injury (TBI) model in larval zebrafish, and its easyTBI induces clinically relevant cell death, haemorrhage & post-traumatic seizuresCa2+ imaging during TBI reveals spike in brain activity concomitant with seizuresTau-GFP Biosensor allows repeated in vivo measures of prion-like tau aggregationpost-TBI, anticonvulsants stop tauopathies akin to Chronic Traumatic Encephalopathy

scholarly journals Rapid disruption of the cortical microcirculation after mild traumatic brain injury

2019 ◽  
Author(s):  
Ellen D. Witkowski ◽  
Şefik Evren Erdener ◽  
Kıvılcım Kılıç ◽  
Sreekanth Kura ◽  
Jianbo Tang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Vascular Dysfunction ◽  
Metabolic Stress ◽  
Time Lapse ◽  
Post Injury ◽  
Injury Model ◽  
Time Lapse Imaging

AbstractTraumatic brain injury (TBI) is a major source of cognitive deficits affecting millions annually. The bulk of human injuries are mild, causing little or no macroscopic damage to neural tissue, yet can still lead to long-term neuropathology manifesting months or years later. Although the cellular stressors that ultimately lead to chronic pathology are poorly defined, one notable candidate is metabolic stress due to reduced cerebral blood flow (CBF), which is common to many forms of TBI. Here we used high-resolution in vivo intracranial imaging in a rodent injury model to characterize deficits in the cortical microcirculation during both acute and chronic phases after mild TBI. We found that CBF dropped precipitously during immediate post-injury periods, decreasing to less than half of baseline levels within minutes and remaining suppressed for 1.5-2 hours. Repeated time-lapse imaging of the cortical microvasculature revealed further striking flow deficits in the capillary network, where 18% of vessels were completely occluded for extended periods after injury, and an additional >50% showed substantial stoppages. Decreased CBF was paralleled by extensive vasoconstriction that is likely to contribute to loss of flow. Our data indicate a major role for vascular dysfunction in even mild forms of TBI, and suggest that acute post-injury periods may be key therapeutic windows for interventions that restore flow and mitigate metabolic stress.

scholarly journals The Functional Status Examination in Mild Traumatic Brain Injury: A TRACK-TBI Sub-Study

2019 ◽  
Vol 34 (7) ◽  
pp. 1165-1174
Author(s):  
Evan Zahniser ◽  
Nancy R Temkin ◽  
Joan Machamer ◽  
Jason Barber ◽  
Geoffrey T Manley ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Functional Status ◽  
Emotional Health ◽  
Functional Limitations ◽  
Well Being ◽  
Functional Impairments ◽  
Post Injury ◽  
Post Traumatic ◽  
Leisure And Recreation

Abstract Objective The Functional Status Examination (FSE) is a comprehensive measure of functional status post-traumatic brain injury (TBI) that has primarily been used in studies of moderate-to-severe TBI. The present observational study examines functional status using the FSE among patients who sustained mild TBIs (mTBIs; defined as Glasgow Coma Scale [GCS] = 13–15 at admission) seen in a Level 1 trauma center. Study aims included examining the course of functional status following mTBI, as well as exploring relationships of the FSE and other relevant constructs among those with GCS = 13–15. Method Participants were assessed at 2 weeks (n = 112), 3 months (n = 113), 6 months (n = 106), and 12 months (n = 88) post-injury for changes in functional status resulting both (a) from all injuries and (b) from TBI only. Results Among seven domains of day-to-day functioning, participants generally experienced the greatest disruption in their primary activity (work or school) and in leisure and recreation. Subjects’ overall functional status tended to improve over time, with sharpest increases in functionality occurring in the first 3 months post-injury. However, some subjects continued to report functional limitations even at 12 months post-injury. Functional status was largely unrelated to neurocognitive functioning, but related strongly to post-traumatic symptoms, life satisfaction, and emotional well-being, particularly at 3 months post-injury and beyond. Conclusion Findings indicate that functional impairments related to mTBI may be more likely to persist than widely believed, with those who experience lingering functional deficits at particular risk for emotional health difficulties.

scholarly journals N-arachidonoyl-L-serine (AraS) Possesses Proneurogenic Properties in Vitro and in Vivo after Traumatic Brain Injury

2013 ◽  
Vol 33 (8) ◽  
pp. 1242-1250 ◽  
Author(s):  
Ayelet Cohen-Yeshurun ◽  
Dafna Willner ◽  
Victoria Trembovler ◽  
Alexander Alexandrovich ◽  
Raphael Mechoulam ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cannabinoid Receptor ◽  
Fold Increase ◽  
Lesion Volume ◽  
Post Injury ◽  
Neuroprotective Effects ◽  
Neurobehavioral Function

N-arachidonoyl-L-serine (AraS) is a novel neuroprotective endocannabinoid. We aimed to test the effects of exogenous AraS on neurogenesis after traumatic brain injury (TBI). The effects of AraS on neural progenitor cells (NPC) proliferation, survival, and differentiation were examined in vitro. Next, mice underwent TBI and were treated with AraS or vehicle. Lesion volumes and clinical outcome were evaluated and the effects on neurogenesis were tested using immunohistochemistry. Treatment with AraS led to a dose-dependent increase in neurosphere size without affecting cell survival. These effects were partially reversed by CB1, CB2, or TRPV1 antagonists. AraS significantly reduced the differentiation of NPC in vitro to astrocytes or neurons and led to a 2.5-fold increase in expression of the NPC marker nestin. Similar effects were observed in vivo in mice treated with AraS 7 days after TBI. These effects were accompanied by a reduction in lesion volume and an improvement in neurobehavioral function compared with controls. AraS increases proliferation of NPCs in vitro in cannabinoid-receptor-mediated mechanisms and maintains NPC in an undifferentiated state in vitro and in vivo. Moreover, although given at 7 days post injury, these effects are associated with significant neuroprotective effects leading to an improvement in neurobehavioral functions.

Duration of post-traumatic amnesia is uniquely associated with memory functioning in chronic moderate-to-severe traumatic brain injury

2021 ◽  
pp. 1-13
Author(s):  
Umesh M. Venkatesan ◽  
Amanda R. Rabinowitz ◽  
Stephanie J. Wolfert ◽  
Frank G. Hillary
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Memory Performance ◽  
Acute Injury ◽  
Post Injury ◽  
Memory Processing ◽  
Memory Functioning ◽  
Traumatic Amnesia ◽  
Post Traumatic ◽  
With Memory

BACKGROUND: Disrupted memory circuitry may contribute to post-traumatic amnesia (PTA) after traumatic brain injury (TBI). It is unclear whether duration of PTA (doPTA) uniquely impacts memory functioning in the chronic post-injury stage. OBJECTIVE: To examine the relationship between doPTA and memory functioning, independent of other cognitive abilities, in chronic moderate-to-severe TBI. METHODS: Participants were 82 individuals (median chronicity = 10.5 years) with available doPTA estimates and neuropsychological data. Composite memory, processing speed (PS), and executive functioning (EF) performance scores, as well as data on subjective memory (SM) beliefs, were extracted. DoPTA-memory associations were evaluated via linear modeling of doPTA with memory performance and clinical memory status (impaired/unimpaired), controlling for PS, EF and demographic covariates. Interrelationships between doPTA, objective memory functioning, and SM were assessed. RESULTS: DoPTA was significantly related to memory performance, even after covariate adjustment. Impairment in memory, but not PS or EF, was associated with a history of longer doPTA. SM was associated with memory performance, but unrelated to doPTA. CONCLUSIONS: Findings suggest a specific association between doPTA—an acute injury phenomenon—and chronic memory deficits after TBI. Prospective studies are needed to understand how underlying mechanisms of PTA shape distinct outcome trajectories, particularly functional abilities related to memory processing.

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