Microglial polarization and the subsequent neuroinflammatory response are contributing factors for traumatic brain injury (TBI)-induced secondary injury. High mobile group box 1 (HMGB1) mediates the ...activation of the NF-κB pathway, and it is considered to be pivotal in the late neuroinflammatory response. Activation of the HMGB1/NF-κB pathway is closely related to HMGB1 acetylation, which is regulated by the sirtuin (SIRT) family of proteins. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are known to have antioxidative and anti-inflammatory effects. We previously demonstrated that ω-3 PUFA inhibited TBI-induced microglial activation and the subsequent neuroinflammatory response by regulating the HMGB1/NF-κB signaling pathway. However, no studies have elucidated if ω-3 PUFA affects the HMGB1/NF-κB pathway in a HMGB1 deacetylation of dependent SIRT1 manner, thus regulating microglial polarization and the subsequent neuroinflammatory response.
The Feeney DM TBI model was adopted to induce brain injury in rats. Modified neurological severity scores, rotarod test, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Assessment of microglia polarization and pro-inflammatory markers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and HMGB1, were used to evaluate the neuroinflammatory responses and the anti-inflammatory effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1/NF-κB signaling pathway activation to evaluate the effects of ω-3 PUFA supplementation. The impact of SIRT1 deacetylase activity on HMGB1 acetylation and the interaction between HMGB1 and SIRT1 were assessed to evaluate anti-inflammation effects of ω-3 PUFAs, and also, whether these effects were dependent on a SIRT1-HMGB1/NF-κB axis to gain further insight into the mechanisms underlying the development of the neuroinflammatory response after TBI.
The results of our study showed that ω-3 PUFA supplementation promoted a shift from the M1 microglial phenotype to the M2 microglial phenotype and inhibited microglial activation, thus reducing TBI-induced inflammatory factors. In addition, ω-3 PUFA-mediated downregulation of HMGB1 acetylation and its extracellular secretion was found to be likely due to increased SIRT1 activity. We also found that treatment with ω-3 PUFA inhibited HMGB1 acetylation and induced direct interactions between SIRT1 and HMGB1 by elevating SIRT1 activity following TBI. These events lead to inhibition of HMGB1 nucleocytoplasmic translocation/extracellular secretion and alleviated HMGB1-mediated activation of the NF-κB pathway following TBI-induced microglial activation, thus inhibiting the subsequent inflammatory response.
The results of this study suggest that ω-3 PUFA supplementation attenuates the inflammatory response by modulating microglial polarization through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway, leading to neuroprotective effects following experimental traumatic brain injury.
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity amongst trauma patients. Its treatment is focused on minimizing progression to secondary injury. Administration of ...propranolol for TBI maydecrease mortality and improve functional outcomes. However, it is our sense that its use has not been universally adopted due to low certainty evidence. The literature was reviewed to explore the mechanism of propranolol as a therapeutic intervention in TBI to guide future clinical investigations. Medline, Embase, and Scopus were searched for studies that investigated the effect of propranolol on TBI in animal models from inception until June 6, 2023. All routes of administration for propranolol were included and the following outcomes were evaluated: cognitive functions, physiological and immunological responses. Screening and data extraction were done independently and in duplicate. The risk of bias for each individual study was assessed using the SYCLE’s risk of bias tool for animal studies. Three hundred twenty-three citations were identified and 14 studies met our eligibility criteria. The data suggests that propranolol may improve post-TBI cognitive and motor function by increasing cerebral perfusion, reducing neural injury, cell death, leukocyte mobilization and p-tau accumulation in animal models. Propranolol may also attenuate TBI-induced immunodeficiency and provide cardioprotective effects by mitigating damage to the myocardium caused by oxidative stress. This systematic review demonstrates that propranolol may be therapeutic in TBI by improving cognitive and motor function while regulating T lymphocyte response and levels of myocardial reactive oxygen species. Oral or intravenous injection of propranolol following TBI is associated with improved cerebral perfusion, reduced neuroinflammation, reduced immunodeficiency, and cardio-neuroprotection in preclinical studies.Oral or intravenous injection of propranolol following TBI is associated with improved cerebral perfusion, reduced neuroinflammation, reduced immunodeficiency, and cardio-neuroprotection in preclinical studies.
Abstract
INTRODUCTION
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Low- and middle-income countries (LMICs) suffer from a high incidence of and mortality from ...TBI. Computed tomography (CT) scan is the diagnostic method of choice, but is often inaccessible in LMICs, where exploratory burr holes (EBH) remain a necessary diagnostic and therapeutic procedure. We sought to describe indications and outcomes of patients undergoing EBH at our sub-Saharan African tertiary care center.
METHODS
We performed a retrospective review of prospectively collected data at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. All trauma patients presenting between June 2012 and July 2015 with a deteriorating level of consciousness and localizing signs who underwent EBH were included. Additionally, we included all patients admitted with TBI, requiring higher-level care during 2011. Because there was no neurosurgeon on staff in 2011, no patients underwent EBH. We performed logistic regression to identify predictors of mortality in the total population of TBI patients.
RESULTS
>241 patients presented to KCH with TBI requiring higher-level care, with a total mortality of 16.4% (Table 1). 163 (68%) underwent EBH. Of patients that underwent EBH, 87.6% of patients had intraoperative findings, with subdural hematoma being the most common (51.2%). Mortality in patients who underwent EBH was 6.8%. In surviving patients who underwent exploratory burr hole, 71.1% had a favorable outcome, defined as good recovery or moderate disability on the Glasgow Outcome Scale. Mortality in patients that did not undergo EBH was 43.9%. Upon logistic regression adjusted for age, sex, and Glasgow Coma Score, not undergoing EBH significantly increased the odds of mortality (OR = 12.0, P = 0.000, 95% CI = 4.48-31.9).
CONCLUSION
EBH remain an important diagnostic and therapeutic procedure for TBI in LMICs. In low-resource settings, EBH technique should be incorporated into general surgery education to attenuate TBI-related mortality.
Abstract
INTRODUCTION
Each year, the annual hospitalization rates of traumatic brain injury (TBI) in children in the US are 57.7/100K less than 5 years of age and 23.1/100K in the 5–14 year age ...group. Although technological advances in multi-modality monitoring allow for high frequency monitoring of the physiological pressure variables, a recent randomised-control trial in adults has questioned the requirement for invasive monitoring. Here in, we describe an objective, non-invasive, quantitative means of stratifying which patients are likely to benefit from invasive monitoring.
METHODS
Radiological biomarkers of TBI (optic nerve sheath diameter; ONSD, basal cistern size, ventricular volume, volume of extra-axial masses, parenchymal oedema) were measured by independent observers and quantified by automatic software (3D slicer, Boston, MA) and correlated with epochs of continuous high frequency variables of pressure monitoring around the time of imaging, in pediatric TBI patients admitted to Cambridge University Hospital (CUH) between January 2009 and December 2016.
RESULTS
>42 patients with a mean age of 10.3 years were admitted to CUH with a TBI and required invasive monitoring. The ICP was 19.6? ±?7.8 mmHg (median±IQR). The presence of subarachnoid blood was related to higher ICP, higher arterial blood pressure, and a trend toward dysfunctional cerebrovascular autoregulation (PRx). Smaller basal cisterns were related to increased ICP (R = −0.42, P = 0.02), impaired PRx (R = −0.5, P = 0.003). The correlation of mean ONSD and max ONSD with ICP was 0.725 (P < 0.0001) and 0.698 (P < 0.0001), respectively.
CONCLUSION
Here we define a set of radiological criteria to help predict the development of unfavourable intracranial pressure variables after a pediatric TBI. The use of objective radiological markers in this model can be tested on an external database to validate the relationship with intracranial pressure.
Abstract
INTRODUCTION
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the US. The effects of TBI on quality of life may not become apparent for years after the injury. ...There are conflicting reports in the literature regarding long term outcomes. Physicians are often asked to predict long term functional and cognitive outcomes, with limited data available.
METHODS
Patients with severe TBI (GCS = 9) who previously participated in a clinical trial during the 1980s were followed up with and compared to healthy controls without history of TBI. A health questionnaire, sports concussion assessment tool version 3 (SCAT3) and the Telephone Interview for Cognitive Status-modified (TICS-m) were completed over the phone and compared with controls using t-test. GCS at admission and 12-month GRS were used to predict to TICS-M at 30 years using linear regression.
RESULTS
>45 of the initial 168 subjects were confirmed alive, and 37 (13 females; mean age: 52.43 years S.D. 10.7) consented. Controls (n = 58; 23 females; mean age = 54 years, S.D. 11.5) had lower symptom severity score (6.7 S.D. 12.6 versus 20.6 S.D. 25.3; P = 0.005), lower total number of symptoms (3.4 S.D. 4.7 versus 7.12 S.D. 6.5; P = 0.006), higher standardized assessment of concussion score (25.6 S.D. 2.8 versus 21.2 S.D. 6.9; P = 0.001), and lower corrected MPAI-4 (22.3 S.D. 17.0 versus 43.7 S.D. 12.8; P < 0.001). GCS at admission did not predict cognitive status at 30-years assessed using TICS-M (P = 0.345). The Glasgow Outcome Scale score at 12-months was correlated to TICS-M at 30 years (R = 0.548, P < 0.001); each point decrease in GOS decreasing the score at TICS-M by 5.6 points.
CONCLUSION
Remote history of TBI disrupts the lives of survivors long after injury. Admission GCS does not predict cognitive status 30 years after TBI. The GOS at 12-months predicted the cognitive status assessed using TICS-M score at 30 years.
Background: We hypothesized that the economic status of a region might influence quality of care and outcome of patients with severe brain trauma. Methods: Between January 2001 and December 2005, 13 ...centres enrolled patients with severe brain trauma. Data on accident, treatment and outcomes were collected prospectively. The regions were classified as ‘high income’ (Austria, five centres), ‘upper middle income’ (UMI) (Croatia, Slovakia, six centres) or ‘lower middle income’ (LMI) (Bosnia, Macedonia, two centres). Data on epidemiology, treatment and outcomes were compared according to this classification. Quality of care was assessed using a new scoring system. Results: A total of 1172 data sets were analysed. Patients from the wealthier regions were significantly older. Low-level falls and traffic accidents contributed to more than two-third of all cases. Violence-related trauma was significantly more frequent in ‘middle income’ regions. Treatment quality was significantly different; treatment according to guidelines for brain trauma management was provided most frequently for patients from high-income regions. Compared with expected mortality rates, mortality was 6.5% lower in the ‘high-income’ centres, 2.4% lower in the ‘UMI’ centres and 13% higher in the ‘LMI’ centres. Advanced age, poor neurological status, high trauma severity and poor quality of care were associated with significantly lower odds for survival. Conclusions: The association between the economic status and outcome of brain trauma patients was due to the quality of care. Successful implementation of guidelines for brain trauma management requires a well-funded health care system.
•Mortality among older adults with moderate to severe TBI was as high as 93 %.•Mortality had a dramatic increase for those ≥80 years old.•No factor was universally associated with increased ...mortality.•Older adults were less likely to be discharged home than younger adults.•Up to 8.4 % of older adults needed professional assistance at home.
This study examined the research on older adults with a moderate to severe traumatic brain injury (TBI), with a focus on mortality and discharge disposition.
Systematic searches were conducted in MEDLINE, CINAHL, EMBASE and PsycINFO for studies up to April 2022 in accordance with PRISMA guidelines.
64 studies, published from 1992 to 2022, met the inclusion criteria. Mortality was higher for older adults ≥60 years old than for their younger counterparts; with a dramatic increase for those ≥80 yr, with rates as high as 93 %. Similar findings were reported regarding mortality in intensive care, surgical mortality, and mortality post-hospital discharge; with an 80 % rate at 1-year post-discharge. Up to 68.4 % of older adults were discharged home; when compared to younger adults, those ≥65 years were less likely to be discharged home (50–51 %), compared to those <64 years (77 %). Older adults were also more likely to be discharged to long-term care (up to 31.6 %), skilled nursing facilities (up to 46.1 %), inpatient rehabilitation (up to 26.9 %), and palliative or hospice care (up to 58 %).
Given their vulnerability, optimizing outcomes for older adults with moderate-severe TBI across the healthcare continuum is critical.
Studies have shown that repetitive transcranial magnetic stimulation (rTMS) can enhance synaptic plasticity and improve neurological dysfunction. However, the mechanism through which rTMS can improve ...moderate traumatic brain injury remains poorly understood. In this study, we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS. To help determine the mechanism of action, we measured levels of several important brain activity-related proteins and their mRNA. On the injured side of the brain, we found that rTMS increased the protein levels and mRNA expression of brain-derived neurotrophic factor, tropomyosin receptor kinase B, N-methyl-D-aspartic acid receptor 1, and phosphorylated cAMP response element binding protein, which are closely associated with the occurrence of long-term potentiation. rTMS also partially reversed the loss of synaptophysin after injury and promoted the remodeling of synaptic ultrastructure. These findings suggest that upregulation of synaptic plasticity-related protein expression is the mechanism through which rTMS promotes neurological function recovery after moderate traumatic brain injury.
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