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Delayed and progressive damages to juvenile mice after moderate traumatic brain injury.

ABSTRACT: Symptoms are commonly more severe in pediatric traumatic brain injury (TBI) patients than in young adult TBI patients. To understand the mechanism, juvenile mice received a controlled cortical impact (CCI) injury at moderate level. Tissue lesion and cell death were measured and compared to our previous reports on brain injury in the young adult mice that received same level of impact using same injury device. Tissue lesion and cell death in the cortex was much less in the juvenile mouse brain in the first few hours after injury. However, once the injury occurred, it developed more rapidly, lasted much longer, and eventually led to exaggerated cell death and a 32.7% larger tissue lesion cavity in the cortex of juvenile mouse brain than of young adult mouse brain. Moreover, we found significant cell death in the thalamus of juvenile brains at 72?h, which was not commonly seen in the young adult mice. In summary, cell death in juvenile mice was delayed, lasted longer, and finally resulted in more severe brain injury than in the young adult mice. The results suggest that pediatric TBI patients may have a longer therapeutic window, but they also need longer intensive clinical care after injury.

SUBMITTER: Zhao S

PROVIDER: S-EPMC5943589 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Delayed and progressive damages to juvenile mice after moderate traumatic brain injury.

Zhao Shu S Wang Xiaoting X Gao Xiang X Chen Jinhui J

Scientific reports 20180509 1

Symptoms are commonly more severe in pediatric traumatic brain injury (TBI) patients than in young adult TBI patients. To understand the mechanism, juvenile mice received a controlled cortical impact (CCI) injury at moderate level. Tissue lesion and cell death were measured and compared to our previous reports on brain injury in the young adult mice that received same level of impact using same injury device. Tissue lesion and cell death in the cortex was much less in the juvenile mouse brain in ...[more]

PMID: 29743575

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Project description:Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the follow-up period, as well as to changes in memory performance, prior to multiple comparison correction. In conclusion, traumatic brain injury results in progressive loss of brain tissue volume, which continues for many years post-injury. Atrophy is most prominent in the white matter, but is also more pronounced in cortical sulci compared to gyri. These findings suggest the Jacobian determinant provides a method of quantifying brain atrophy following a traumatic brain injury and is informative in determining the long-term neurodegenerative effects after injury. Power calculations indicate that Jacobian determinant images are an efficient surrogate marker in clinical trials of neuroprotective therapeutics.

Project description:ObjectivesAfter traumatic brain injury, continuous electroencephalography is widely used to detect electrographic seizures. With the development of standardized continuous electroencephalography terminology, we aimed to describe the prevalence and burden of ictal-interictal patterns, including electrographic seizures after moderate-to-severe traumatic brain injury and to correlate continuous electroencephalography features with functional outcome.DesignPost hoc analysis of the prospective, randomized controlled phase 2 multicenter INTREPID study (ClinicalTrials.gov: NCT00805818). Continuous electroencephalography was initiated upon admission to the ICU. The primary outcome was the 3-month Glasgow Outcome Scale-Extended. Consensus electroencephalography reviews were performed by raters certified in standardized continuous electroencephalography terminology blinded to clinical data. Rhythmic, periodic, or ictal patterns were referred to as "ictal-interictal continuum"; severe ictal-interictal continuum was defined as greater than or equal to 1.5 Hz lateralized rhythmic delta activity or generalized periodic discharges and any lateralized periodic discharges or electrographic seizures.SettingTwenty U.S. level I trauma centers.PatientsPatients with nonpenetrating traumatic brain injury and postresuscitation Glasgow Coma Scale score of 4-12 were included.InterventionsNone.Measurements and main resultsAmong 152 patients with continuous electroencephalography (age 34 ± 14 yr; 88% male), 22 (14%) had severe ictal-interictal continuum including electrographic seizures in four (2.6%). Severe ictal-interictal continuum burden correlated with initial prognostic scores, including the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (r = 0.51; p = 0.01) and Injury Severity Score (r = 0.49; p = 0.01), but not with functional outcome. After controlling clinical covariates, unfavorable outcome was independently associated with absence of posterior dominant rhythm (common odds ratio, 3.38; 95% CI, 1.30-9.09), absence of N2 sleep transients (3.69; 1.69-8.20), predominant delta activity (2.82; 1.32-6.10), and discontinuous background (5.33; 2.28-12.96) within the first 72 hours of monitoring.ConclusionsSevere ictal-interictal continuum patterns, including electrographic seizures, were associated with clinical markers of injury severity but not functional outcome in this prospective cohort of patients with moderate-to-severe traumatic brain injury. Importantly, continuous electroencephalography background features were independently associated with functional outcome and improved the area under the curve of existing, validated predictive models.

Project description:OBJECTIVES:To characterize admission patterns, treatments, and outcomes among patients with moderate traumatic brain injury. DESIGN:Retrospective cohort study. SETTING:National Trauma Data Bank. PATIENTS:Adults (age > 18 yr) with moderate traumatic brain injury (International Classification of Diseases, Ninth revision codes and admission Glasgow Coma Scale score of 9-13) in the National Trauma Data Bank between 2007 and 2014. INTERVENTIONS:None. MEASUREMENT AND MAIN RESULTS:Demographics, mechanism of injury, hospital course, and facility characteristics were examined. Admission characteristics associated with discharge outcomes were analyzed using multivariable Poisson regression models. Of 114,066 patients, most were white (62%), male (69%), and had median admission Glasgow Coma Scale score of 12 (interquartile range, 10-13). Seventy-seven percent had isolated traumatic brain injury. Concussion, which accounted for 25% of moderate traumatic brain injury, was the most frequent traumatic brain injury diagnosis. Fourteen percent received mechanical ventilation, and 66% were admitted to ICU. Over 50% received care at a community hospital. Seven percent died, and 32% had a poor outcome, including those with Glasgow Coma Scale score of 13. Compared with patients 18-44 years, patients 45-64 years were twice as likely (adjusted relative risk, 1.97; 95% CI, 1.92-2.02) and patients over 80 years were five times as likely (adjusted relative risk, 4.66; 95% CI, 4.55-4.76) to have a poor outcome. Patients with a poor discharge outcome were more likely to have had hypotension at admission (adjusted relative risk, 1.10; 95% CI, 1.06-1.14), lower admission Glasgow Coma Scale (adjusted relative risk, 1.37; 95% CI, 1.34-1.40), higher Injury Severity Score (adjusted relative risk, 2.97; 95% CI, 2.86-3.09), and polytrauma (adjusted relative risk, 1.05; 95% CI, 1.02-1.07), compared with those without poor discharge outcomes. CONCLUSIONS:Many patients with moderate traumatic brain injury deteriorate, require neurocritical care, and experience poor outcomes. Optimization of care and outcomes for this vulnerable group of patients are urgently needed.

Project description:OBJECT There is limited literature available to guide transfusion practices for patients with severe traumatic brain injury (TBI). Recent studies have shown that maintaining a higher hemoglobin threshold after severe TBI offers no clinical benefit. The present study aimed to determine if a higher transfusion threshold was independently associated with an increased risk of progressive hemorrhagic injury (PHI), thereby contributing to higher rates of morbidity and mortality. METHODS The authors performed a secondary analysis of data obtained from a recently performed randomized clinical trial studying the effects of erythropoietin and blood transfusions on neurological recovery after severe TBI. Assigned hemoglobin thresholds (10 g/dl vs 7 g/dl) were maintained with packed red blood cell transfusions during the acute phase after injury. PHI was defined as the presence of new or enlarging intracranial hematomas on CT as long as 10 days after injury. A severe PHI was defined as an event that required an escalation of medical management or surgical intervention. Clinical and imaging parameters and transfusion thresholds were used in a multivariate Cox regression analysis to identify independent risk factors for PHI. RESULTS Among 200 patients enrolled in the trial, PHI was detected in 61 patients (30.5%). The majority of patients with PHI had a new, delayed contusion (n = 29) or an increase in contusion size (n = 15). The mean time interval between injury and identification of PHI was 17.2 ± 15.8 hours. The adjusted risk of severe PHI was 2.3 times higher for patients with a transfusion threshold of 10 g/dl (95% confidence interval 1.1-4.7; p = 0.02). Diffuse brain injury was associated with a lower risk of PHI events, whereas higher initial intracranial pressure increased the risk of PHI (p < 0.001). PHI was associated with a longer median length of stay in the intensive care unit (18.3 vs 14.4 days, respectively; p = 0.04) and poorer Glasgow Outcome Scale scores (42.9% vs 25.5%, respectively; p = 0.02) at 6 months. CONCLUSIONS A higher transfusion threshold of 10 g/dl after severe TBI increased the risk of severe PHI events. These results indicate the potential adverse effect of using a higher hemoglobin transfusion threshold after severe TBI.

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Delayed and progressive damages to juvenile mice after moderate traumatic brain injury.

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Delayed and progressive damages to juvenile mice after moderate traumatic brain injury.

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