Dataset Information

Pathophysiological and behavioral deficits in developing mice following rotational acceleration-deceleration traumatic brain injury.

ABSTRACT: Abusive head trauma (AHT) is the leading cause of death from trauma in infants and young children. An AHT animal model was developed on 12-day-old mice subjected to 90° head extension-flexion sagittal shaking repeated 30, 60, 80 and 100 times. The mortality and time until return of consciousness were dependent on the number of repeats and severity of the injury. Following 60 episodes of repeated head shakings, the pups demonstrated apnea and/or bradycardia immediately after injury. Acute oxygen desaturation was observed by pulse oximetry during respiratory and cardiac suppression. The cerebral blood perfusion was assessed by laser speckle contrast analysis (LASCA) using a PeriCam PSI system. There was a severe reduction in cerebral blood perfusion immediately after the trauma that did not significantly improve within 24?h. The injured mice began to experience reversible sensorimotor function at 9?days postinjury (dpi), which had completely recovered at 28?dpi. However, cognitive deficits and anxiety-like behavior remained. Subdural/subarachnoid hemorrhage, damage to the brain-blood barrier and parenchymal edema were found in all pups subjected to 60 insults. Proinflammatory response and reactive gliosis were upregulated at 3?dpi. Degenerated neurons were found in the cerebral cortex and olfactory tubercles at 30?dpi. This mouse model of repetitive brain injury by rotational head acceleration-deceleration partially mimics the major pathophysiological and behavioral events that occur in children with AHT. The resultant hypoxia/ischemia suggests a potential mechanism underlying the secondary rotational acceleration-deceleration-induced brain injury in developing mice.

SUBMITTER: Wang G

PROVIDER: S-EPMC5818073 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Pathophysiological and behavioral deficits in developing mice following rotational acceleration-deceleration traumatic brain injury.

Wang Guoxiang G Zhang Yi Ping YP Gao Zhongwen Z Shields Lisa B E LBE Li Fang F Chu Tianci T Lv Huayi H Moriarty Thomas T Xu Xiao-Ming XM Yang Xiaoyu X Shields Christopher B CB Cai Jun J

Disease models & mechanisms 20180130 1

Abusive head trauma (AHT) is the leading cause of death from trauma in infants and young children. An AHT animal model was developed on 12-day-old mice subjected to 90° head extension-flexion sagittal shaking repeated 30, 60, 80 and 100 times. The mortality and time until return of consciousness were dependent on the number of repeats and severity of the injury. Following 60 episodes of repeated head shakings, the pups demonstrated apnea and/or bradycardia immediately after injury. Acute oxygen ...[more]

PMID: 29208736

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Project description:Purpose This study examined auditory deficits and symptom reporting in individuals with long-term postconcussion symptoms following a single mild traumatic brain injury (mTBI) compared to age- and gender-matched controls without a history of mTBI. Method Case history interviews, symptom questionnaires, and a battery of central auditory and neuropsychological tests were administered to 2 groups. The mTBI group was a civilian population recruited from a local concussion management program who were seeking rehabilitation for postconcussion-related problems in a postacute period between 3 and 18 months following injury. Symptom validity testing was included to assess the rate of possible insufficient test effort and its influence on scores for all outcome measures. Analyses of group differences in test scores were performed both with and without the participants who showed insufficient test effort. Rates of symptom reporting, correlations among symptoms and behavioral test outcomes, and the relationships between auditory and cognitive test performance were analyzed. Results The mTBI group reported a high rate of auditory symptoms and general postconcussion symptoms. Performance on neuropsychological tests of cognitive function showed some differences in raw scores between groups, but when effort was considered, there were no significant differences in the rate of abnormal performance between groups. In contrast, there were significant differences in both raw scores and the rate of abnormal performance between groups for some auditory tests when only considering participants with sufficient effort. Auditory symptoms were strongly correlated with other general postconcussion symptoms. Conclusions Significant auditory symptoms and evidence of long-term central auditory dysfunction were found in a subset of individuals who had chronic postconcussion symptoms after a single mTBI unrelated to blast trauma. The rate of abnormal performance on auditory behavioral tests exceeded the rate of abnormal performance on tests of cognitive function. Supplemental Material https://doi.org/10.23641/asha.8329955.

Project description:Despite the life-long implications of social and communication dysfunction after pediatric traumatic brain injury, there is a poor understanding of these deficits in terms of their developmental trajectory and underlying mechanisms. In a well-characterized murine model of pediatric brain injury, we recently demonstrated that pronounced deficits in social interactions emerge across maturation to adulthood after injury at postnatal day (p) 21, approximating a toddler-aged child. Extending these findings, we here hypothesized that these social deficits are dependent upon brain maturation at the time of injury, and coincide with abnormal sociosexual behaviors and communication. Age-dependent vulnerability of the developing brain to social deficits was addressed by comparing behavioral and neuroanatomical outcomes in mice injured at either a pediatric age (p21) or during adolescence (p35). Sociosexual behaviors including social investigation and mounting were evaluated in a resident-intruder paradigm at adulthood. These outcomes were complemented by assays of urine scent marking and ultrasonic vocalizations as indices of social communication. We provide evidence of sociosexual deficits after brain injury at p21, which manifest as reduced mounting behavior and scent marking towards an unfamiliar female at adulthood. In contrast, with the exception of the loss of social recognition in a three-chamber social approach task, mice that received TBI at adolescence were remarkably resilient to social deficits at adulthood. Increased emission of ultrasonic vocalizations (USVs) as well as preferential emission of high frequency USVs after injury was dependent upon both the stimulus and prior social experience. Contrary to the hypothesis that changes in white matter volume may underlie social dysfunction, injury at both p21 and p35 resulted in a similar degree of atrophy of the corpus callosum by adulthood. However, loss of hippocampal tissue was greater after p21 compared to p35 injury, suggesting that a longer period of lesion progression or differences in the kinetics of secondary pathogenesis after p21 injury may contribute to observed behavioral differences. Together, these findings indicate vulnerability of the developing brain to social dysfunction, and suggest that a younger age-at-insult results in poorer social and sociosexual outcomes.

Dataset Information

Pathophysiological and behavioral deficits in developing mice following rotational acceleration-deceleration traumatic brain injury.

Publications

Pathophysiological and behavioral deficits in developing mice following rotational acceleration-deceleration traumatic brain injury.

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