A Histological and Morphometric Assessment of the Adult and Juvenile Rat Livers after Mild Traumatic Brain Injury.
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ABSTRACT:
SUBMITTER: Prus R
PROVIDER: S-EPMC8148537 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Morphometric changes in cortical thickness (CT), cortical surface area (CSA), and cortical volume (CV) can reflect pathological changes after acute mild traumatic brain injury (mTBI). Most previous studies focused on changes in CT, CSA, and CV in subacute or chronic mTBI, and few studies have examined changes in CT, CSA, and CV in acute mTBI. Furthermore, acute mTBI patients typically show transient cognitive impairment, and few studies have reported on the relationship between cerebral morphological changes and cognitive function in patients with mTBI. This prospective cohort study included 30 patients with acute mTBI (15 males, 15 females, mean age 33.7 years) and 27 matched healthy controls (12 males, 15 females, mean age 37.7 years) who were recruited from the Second Xiangya Hospital of Central South University between September and December 2019. High-resolution T1-weighted images were acquired within 7 days after the onset of mTBI. The results of analyses using FreeSurfer software revealed significantly increased CSA and CV in the right lateral occipital gyrus of acute-stage mTBI patients compared with healthy controls, but no significant changes in CT. The acute-stage mTBI patients also showed reduced executive function and processing speed indicated by a lower score in the Digital Symbol Substitution Test, and reduced cognitive ability indicated by a longer time to complete the Trail Making Test-B. Both increased CSA and CV in the right lateral occipital gyrus were negatively correlated with performance in the Trail Making Test part A. These findings suggest that cognitive deficits and cortical alterations in CSA and CV can be detected in the acute stage of mTBI, and that increased CSA and CV in the right lateral occipital gyrus may be a compensatory mechanism for cognitive dysfunction in acute-stage mTBI patients. This study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University, China (approval No. 086) on February 9, 2019.
| S-EPMC8504398 | biostudies-literature
Project description:Reduced integrity of white matter (WM) pathways and subtle anomalies in gray matter (GM) morphology have been hypothesized as mechanisms in mild traumatic brain injury (mTBI). However, findings on structural brain changes in early stages after mTBI are inconsistent and findings related to early symptoms severity are rare. Fifty-one patients were assessed with multimodal neuroimaging and clinical methods exclusively within 7 days following mTBI and compared to 53 controls. Whole-brain connectivity based on diffusion tensor imaging was subjected to network-based statistics, whereas cortical surface area, thickness, and volume based on T1-weighted MRI scans were investigated using surface-based morphometric analysis. Reduced connectivity strength within a subnetwork of 59 edges located predominantly in bilateral frontal lobes was significantly associated with higher levels of self-reported symptoms. In addition, cortical surface area decreases were associated with stronger complaints in five clusters located in bilateral frontal and postcentral cortices, and in the right inferior temporal region. Alterations in WM and GM were localized in similar brain regions and moderately-to-strongly related to each other. Furthermore, the reduction of cortical surface area in the frontal regions was correlated with poorer attentive-executive performance in the mTBI group. Finally, group differences were detected in both the WM and GM, especially when focusing on a subgroup of patients with greater complaints, indicating the importance of classifying mTBI patients according to severity of symptoms. This study provides evidence that mTBI affects not only the integrity of WM networks by means of axonal damage but also the morphology of the cortex during the initial post-injury period. These anomalies might be greater in the acute period than previously believed and the involvement of frontal brain regions was consistently pronounced in both findings. The dysconnected subnetwork suggests that mTBI can be conceptualized as a dysconnection syndrome. It remains unclear whether reduced WM integrity is the trigger for changes in cortical surface area or whether tissue deformations are the direct result of mechanical forces acting on the brain. The findings suggest that rapid identification of high-risk patients with the use of clinical scales should be assessed acutely as part of the mTBI protocol.
| S-EPMC4809899 | biostudies-literature
Project description:Traumatic brain injury (TBI) poses a major health challenge, with tens of millions of new cases reported globally every year. Brain damage resulting from TBI can vary significantly due to factors including injury severity, injury mechanism and exposure to repeated injury events. Therefore, there is need for robust blood biomarkers. Serum from Sprague Dawley rats was collected at several timepoints within 24 h of mild single or repeat closed head impacts. Serum samples were analyzed via ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) in positive and negative ion modes. Known lipid species were identified through matching to in-house tandem MS databases. Lipid biomarkers have a unique potential to serve as objective molecular measures of injury response as they may be liberated to circulation more readily than larger protein markers. Machine learning and feature selection approaches were used to construct lipid panels capable of distinguishing serum from injured and uninjured rats. The best multivariate lipid panels had over 90% cross-validated sensitivity, selectivity, and accuracy. These mapped onto sphingolipid signaling, autophagy, necroptosis and glycerophospholipid metabolism pathways, with Benjamini adjusted p-values less than 0.05. The novel lipid biomarker candidates identified provide insight into the metabolic pathways altered within 24 h of mild TBI.
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Project description:Modeling juvenile traumatic brain injury (TBI) in rodents presents several unique challenges compared to adult TBI, one of which is selecting appropriate sensorimotor behavioral tasks that enable the assessment of the extent of injury and recovery over time in developing animals. To address this challenge, we performed a comparison of common sensorimotor tests in Long-Evans rats of various sizes and developmental stages (postnatal days 16-45, 35-190 g). Tests were compared and selected for their developmental appropriateness, scalability for growth, pre-training requirements, and throughput capability. Sex differences in response to TBI were also assessed. Grid walk, automated gait analysis, rotarod, beam walk, spontaneous forelimb elevation test, and measurement of motor activity using the force-plate actometer were evaluated. Grid walk, gait analysis, and rotarod failed to meet one or more of the evaluation criteria. Beam walk, spontaneous forelimb elevation test, and measurement of motor activity using the force-plate actometer satisfied all criteria and were capable of detecting motor abnormalities in rats subjected to controlled cortical impact on postnatal day 17. No sex differences were detected in the acute effects of TBI or functional recovery during the 28 days after injury using these tests. This demonstrates the utility of these tests for the evaluation of sensorimotor function in studies using rat models of pediatric TBI, and suggests that pre-pubertal males and females respond similarly to TBI with respect to sensorimotor outcomes.
| S-EPMC3142868 | biostudies-literature
Project description:Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used water pressure or rotational injury for designing the device to make a rat a mild traumatic brain injury model. The objective of this study was to make a simple model of causing mild traumatic brain injury in rats. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175 g) was freely dropped 30 cm to rat's skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague-Dawley rats, we performed magnetic resonance imaging (MRI) of the brain within 24 h after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. The absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain injury. However, the difference of the ratio was a less than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rats. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury.
| S-EPMC5214841 | biostudies-literature
Project description:Traumatic brain injury (TBI) refers to physical trauma to the brain that can lead to motor and cognitive dysfunctions. TBI is particularly serious in infants and young children, often leading to long-term functional impairments. Although clinical research is useful for quantifying and observing the effects of these injuries, few studies have empirically assessed the long-term effects of juvenile TBI (jTBI) on behavior and histology. After a controlled cortical impact delivered to postnatal 17day old rats, functional abilities were measured after 3, 5, and 6months using open field (activity levels), zero maze (anxiety-like behaviors), rotarod (sensorimotor abilities, coordination, and balance), and water maze (spatial learning and memory, swim speed, turn bias). Sensorimotor function was impaired for up to 6months in jTBI animals, which showed no improvement from repeated test exposure. Although spatial learning was not impaired, spatial memory deficits were observed in jTBI animals starting at 3months after injury. Magnetic resonance imaging and histological data revealed that the effects of jTBI were evolving for up to 6months post-injury, with reduced cortical thickness, decreased corpus callosum area and CA1 neuronal cell death in jTBI animals distant to the impact site. These findings suggest that this model of jTBI produces long-term impairments comparable to those reported clinically. Although some deficits were stable over time, the variable nature of other deficits (e.g., memory) as well as changing properties of the lesion itself, suggest that the effects of a single jTBI produce a chronic brain disorder with long-term complications.
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Project description:Cortical gyrification, as a specific measure derived from magnetic resonance imaging, remains understudied in mild traumatic brain injury (mTBI). Local gyrification index (lGI) and mean curvature are related measures indexing the patterned folding of the cortex,ml which reflect distinct properties of cortical morphology and geometry. Using both metrics, we examined cortical gyrification morphology in 59 adult males with mTBI (n = 29) versus those without (n = 30) mTBI in the subacute phase of injury (between 2 weeks and 3 months). The effect of IQ on lGI and brain-symptom relations were also examined. General linear models revealed greater lGI in mTBI versus controls in the frontal lobes bilaterally, but reduced lGI in mTBI of the left temporal lobe. An age-related decrease in lGI was found in numerous areas, with no significant group-by-age interaction effects observed. Including other factors (i.e., mTBI severity, symptoms, and IQ) in the lGI model yielded similar results with few exceptions. Mean curvature analyses depicted a significant group-by-age interaction with the absence of significant main effects of group or age. Our results suggest that cortical gyrification morphology is adversely affected by mTBI in both frontal and temporal lobes, which are thought of as highly susceptible regions to mTBI. These findings contribute to understanding the effects of mTBI on neuromorphological properties, such as alterations in cortical gyrification, which reflect underlying microstructural changes (i.e., apoptosis, neuronal number, or white matter alterations). Future studies are needed to infer causal relationships between micro- and macrostructural changes after an mTBI and investigate potential sex differences.
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Project description:Our study investigates the potential of diffusion MRI (dMRI), including diffusion tensor imaging (DTI), fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI), to detect microstructural tissue abnormalities in rats after mild traumatic brain injury (mTBI). The brains of sham-operated and mTBI rats 35 days after lateral fluid percussion injury were imaged ex vivo in a 11.7-T scanner. Voxel-based analyses of DTI-, fixel- and NODDI-based metrics detected extensive tissue changes in directly affected brain areas close to the primary injury, and more importantly, also in distal areas connected to primary injury and indirectly affected by the secondary injury mechanisms. Histology revealed ongoing axonal abnormalities and inflammation, 35 days after the injury, in the brain areas highlighted in the group analyses. Fractional anisotropy (FA), fiber density (FD) and fiber density and fiber bundle cross-section (FDC) showed similar pattern of significant areas throughout the brain; however, FA showed more significant voxels in gray matter areas, while FD and FDC in white matter areas, and orientation dispersion index (ODI) in areas most damage based on histology. Region-of-interest (ROI)-based analyses on dMRI maps and histology in selected brain regions revealed that the changes in MRI parameters could be attributed to both alterations in myelinated fiber bundles and increased cellularity. This study demonstrates that the combination of dMRI methods can provide a more complete insight into the microstructural alterations in white and gray matter after mTBI, which may aid diagnosis and prognosis following a mild brain injury.
| S-EPMC8662623 | biostudies-literature
Project description:Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CP-mag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM-tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 h after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. From the clinical editor: In this study, chitosan and PEI-coated magnetic micelles (CPMM) were demonstrated as potentially useful vehicles in traumatic brain injury in a rodent model. Magnetofection increased the concentration of CPMMs in the brain and, after intranasal delivery, CPMM did not evoke any inflammatory response and were excreted from the body.
| S-EPMC4338919 | biostudies-literature
Project description:Traumatic brain injury (TBI) can be serious partly due to the challenges of assessing and treating its neurocognitive and affective sequelae. The effects of a single TBI may persist for years and can limit patients' activities due to somatic complaints (headaches, vertigo, sleep disturbances, nausea, light or sound sensitivity), affective sequelae (post-traumatic depressive symptoms, anxiety, irritability, emotional instability) and mild cognitive impairment (MCI, including social cognition disturbances, attention deficits, information processing speed decreases, memory degradation and executive dysfunction). Despite a growing amount of research, study comparison and knowledge synthesis in this field are problematic due to TBI heterogeneity and factors like injury mechanism, age at or time since injury. The relative lack of standardization in neuropsychological assessment strategies for quantifying sequelae adds to these challenges, and the proper administration of neuropsychological testing relative to the relationship between TBI, MCI and neuroimaging has not been reviewed satisfactorily. Social cognition impairments after TBI (e.g., disturbed emotion recognition, theory of mind impairment, altered self-awareness) and their neuroimaging correlates have not been explored thoroughly. This review consolidates recent findings on the cognitive and affective consequences of TBI in relation to neuropsychological testing strategies, to neurobiological and neuroimaging correlates, and to patient age at and assessment time after injury. All cognitive domains recognized by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) are reviewed, including social cognition, complex attention, learning and memory, executive function, language and perceptual-motor function. Affect and effort are additionally discussed owing to their relationships to cognition and to their potentially confounding effects. Our findings highlight non-negligible cognitive and affective impairments following TBI, their gravity often increasing with injury severity. Future research should study (A) language, executive and perceptual-motor function (whose evolution post-TBI remains under-explored), (B) the effects of age at and time since injury, and (C) cognitive impairment severity as a function of injury severity. Such efforts should aim to develop and standardize batteries for cognitive subdomains-rather than only domains-with high ecological validity. Additionally, they should utilize multivariate techniques like factor analysis and related methods to clarify which cognitive subdomains or components are indeed measured by standardized tests.
| S-EPMC7358255 | biostudies-literature