Tissue vulnerability is increased following repetitive mild traumatic brain injury in the rat

Huang, Lei; Coats, Jacqueline S.; Mohd-Yusof, Alena; Yin, Yufang; Assaad, Sarah; Muellner, Michael J.; Kamper, Joel E.; Hartman, Richard E.; Dulcich, Melissa S.; Donovan, Virginia; Oyoyo, Udo; Obenaus, André

doi:10.1016/j.brainres.2012.12.038

Cited by 45 publications

(42 citation statements)

References 49 publications

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“…Serum GFAP levels predict the clinical outcome of mTBI in children [38]. Consistent with previous studies using immunochemical staining and immunoblot analysis [27,34], our real-time RT-PCR studies showed an increased expression of GFAP in the impacted compared with control brain, suggesting that secondary damage might have been underway. We also evaluated the expression of Hsp70, a stress-inducible heat shock protein.…”

Section: Discussionsupporting

confidence: 90%

“…One of the immediate effects in mTBI is brain microhemorrhage. Hemorrhagic volumes determined by a magnetic resonance imaging method with the distribution of extracellular iron as the result of following TBI was found to be correlated with red blood cell accumulation and degradation [34]. Although we indeed found significantly higher Prussian blue staining scores in the impacted versus control mice, indicating that the impact caused more iron deposition and hemorrhage, the Prussian blue staining was mostly localized in just a few areas beneath the impact area on the dorsal side and was not widespread in the brain.…”

Section: Discussionmentioning

confidence: 94%

“…The brain sections were then mounted on slides and stained. Prussian blue is a stain that identifies iron in brain tissues, indicating presence of a minor hemorrhage [34]. The…”

Section: Brain Histological Analysismentioning

confidence: 99%

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Reduced bone mass accrual in mouse model of repetitive mild traumatic brain injury

Yu¹,

Wergedal²,

Rundle³

et al. 2014

J Rehabil Res Dev

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Abstract-Traumatic brain injury (TBI) can affect bone by influencing the production/actions of pituitary hormones and neuropeptides that play significant regulatory roles in bone metabolism. Previously, we demonstrated that experimental TBI exerted a negative effect on the skeleton. Since mild TBI (mTBI) accounts for the majority of TBI cases, this study was undertaken to evaluate TBI effects using a milder impact model in female mice. Repetitive mTBI caused microhemorrhaging, astrocytosis, and increased anti-inflammatory protective actions in the brain of the impacted versus control mice 2 wk after the first impact. Serum levels of growth regulating insulin-like growth factor 1 (IGF-1) were reduced by 28.9%. Bone mass was reduced significantly in total body as well as individual skeletons. Tibial total cortical density was reduced by 7.0%, which led to weaker bones, as shown by a 31.3% decrease in femoral size adjusted peak torque. A 27.5% decrease in tibial trabecular bone volume per total volume was accompanied by a 34.3% (p = 0.07) decrease in bone formation rate (BFR) per total area. Based on our data, we conclude that repetitive mTBI exerted significant negative effects on accrual of both cortical and trabecular bone mass in mice caused by a reduced BFR.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 94%

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Reduced bone mass accrual in mouse model of repetitive mild traumatic brain injury

Yu¹,

Wergedal²,

Rundle³

et al. 2014

J Rehabil Res Dev

View full text Add to dashboard Cite

show abstract

“…In general, increasing the interinjury interval reduces physical, cognitive, and behavioral sequelae, as well as mortality (Kanayama et al 1996; Meehan et al 2012; Huang et al 2013; Weil et al 2014; Bolton Hall et al 2016). For example, the mortality percentage is significantly lower for piglets subjected to primary injuries 1 wk apart compared with 1 d apart (Friess et al 2009).…”

Section: Resultsmentioning

confidence: 99%

“…In humans and flies, the probability of mortality following TBI is associated with age and blood/hemolymph glucose level, which is influenced by diet (Susman et al 2002; Hukkelhoven et al 2003; Griesdale et al 2009; Dhandapani et al 2012; Katzenberger et al 2013, 2015a; Wang et al 2013; Borsage et al 2015; Chong et al 2015). Furthermore, studies of repetitive primary injuries in mammals and flies indicate that the time between primary injuries can affect the probability of mortality (Kanayama et al 1996; Friess et al 2009; Meehan et al 2012; Huang et al 2013; Weil et al 2014; Bolton Hall et al 2016) (Figure 1 and Figure 3). Thus, evolutionarily conserved age-, diet-, and interinjury interval-regulated mechanisms appear to promote secondary injuries that cause mortality.…”

Section: Discussionmentioning

confidence: 99%

Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

Katzenberger

Ganetzky

Wassarman

2016

G3 Genes|Genomes|Genetics

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Outcomes of traumatic brain injury (TBI) vary because of differences in primary and secondary injuries. Primary injuries occur at the time of a traumatic event, whereas secondary injuries occur later as a result of cellular and molecular events activated in the brain and other tissues by primary injuries. We used a Drosophila melanogaster TBI model to investigate secondary injuries that cause acute mortality. By analyzing mortality percentage within 24 hr of primary injuries, we previously found that age at the time of primary injuries and diet afterward affect the severity of secondary injuries. Here, we show that secondary injuries peaked in activity 1–8 hr after primary injuries. Additionally, we demonstrate that age and diet activated distinct secondary injuries in a genotype-specific manner, and that concurrent activation of age- and diet-regulated secondary injuries synergistically increased mortality. To identify genes involved in secondary injuries that cause mortality, we compared genome-wide mRNA expression profiles of uninjured and injured flies under age and diet conditions that had different mortalities. During the peak period of secondary injuries, innate immune response genes were the predominant class of genes that changed expression. Furthermore, age and diet affected the magnitude of the change in expression of some innate immune response genes, suggesting roles for these genes in inhibiting secondary injuries that cause mortality. Our results indicate that the complexity of TBI outcomes is due in part to distinct, genetically controlled, age- and diet-regulated mechanisms that promote secondary injuries and that involve a subset of innate immune response genes.

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Patterns of Behavioral Deficits in Rodents Following Brain Injury Across Species, Gender, and Experimental Model

Hartman

Thorndyke

2016

Acta Neurochirurgica Supplement

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Behavioral data were collected from several hundred mice and rats using a variety of experimental models of brain injury. The use of consistent protocols allowed compilation of these data, facilitating analyses of animal behaviors across experimental models, species, and gender. Spatial learning and sensorimotor/coordination data are presented, suggesting that, in general, rats performed better than mice both in the water maze and on the rotarod. Compared with females, males performed slightly better in the water maze and slightly worse on the rotarod. However, gender by species interactions accounted for both of these differences. Male rats performed better in the water maze than female rats, male mice, and female mice, which did not differ. Male mice performed worse on the rotarod than female mice, male rats, and female rats, which performed similarly. Furthermore, animals with subcortical injury were impaired in the water maze, but performed better than animals with cortical injuries. However, only animals with cortical injuries were impaired on the rotarod. Additional covariates, such as edema and lesion size, may further clarify these phenotypes. Overall, we provide evidence that abbreviated test batteries can be specifically designed to test deficits, depending on the species, gender, and model.

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Tissue vulnerability is increased following repetitive mild traumatic brain injury in the rat

Cited by 45 publications

References 49 publications

Reduced bone mass accrual in mouse model of repetitive mild traumatic brain injury

Reduced bone mass accrual in mouse model of repetitive mild traumatic brain injury

Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

Patterns of Behavioral Deficits in Rodents Following Brain Injury Across Species, Gender, and Experimental Model

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