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New method to induce mild traumatic brain injury in rodents produces differential outcomes in female and male Sprague Dawley rats.

ABSTRACT: BACKGROUND:Mild traumatic brain injuries (mTBI) are an increasing health concern due to persistent behavioral and neurological effects. To better understand these effects, researchers frequently rely on animal injury models. Existing models, however, may not adequately reproduce the mechanism of injury as it occurs in humans. NEW METHOD:Our new model for inducing mTBI in rodents entails acceleration of the animal toward a stationary impact zone to produce rapid rotational movement of the head. The aim of the present experiment was to characterize the effects of this injury in female and male rats on behavior, cognition, and neural plasticity. RESULTS:mTBI produced the most widespread effects in females: they were more active during recovery within minutes of mTBI and more active in the center of the open field 4days after mTBI. Spatial learning deficits in the water maze were mild but persistent and accompanied by reduced numbers of immature neurons in the hippocampus along with reductions in sera levels of the neurotrophin, BDNF. By contrast, male mTBI rats mainly exhibited mild spatial learning deficits, with no other observed effects. COMPARISON WITH EXISTING METHODS:Our model induced effects on behavior and biology in rats that aligned with existing models. However, new patterns were observed, particularly when comparing females and males. CONCLUSIONS:Taken together, these findings confirm the validity of this model and point to key differences between females and males in symptom severity and type. Additionally, our model adds a novel injury mechanism that complements existing rodent models.

SUBMITTER: Wirth P

PROVIDER: S-EPMC5790318 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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New method to induce mild traumatic brain injury in rodents produces differential outcomes in female and male Sprague Dawley rats.

Wirth Peter P Yu Waylin W Kimball Amanda L AL Liao Jennifer J Berkner Paul P Glenn Melissa J MJ

Journal of neuroscience methods 20170802

<h4>Background</h4>Mild traumatic brain injuries (mTBI) are an increasing health concern due to persistent behavioral and neurological effects. To better understand these effects, researchers frequently rely on animal injury models. Existing models, however, may not adequately reproduce the mechanism of injury as it occurs in humans.<h4>New method</h4>Our new model for inducing mTBI in rodents entails acceleration of the animal toward a stationary impact zone to produce rapid rotational movement ...[more]

PMID: 28780369

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Project description:Polychlorinated biphenyls (PCBs) are organic chemicals that were traditionally produced and widely used in industry as mixtures and are presently formed as byproducts of pigment and dye manufacturing. They are known to persist and bioaccumulate in the environment. Some have been shown to induce liver cancer in rodents. Although the mechanism of the toxicity of PCBs is unknown, it has been shown that they increase oxidative stress, including lipid peroxidation. We hypothesized that oxidative stress-induced DNA damage could be a contributor for PCB carcinogenesis and analyzed several DNA adducts in female Sprague-Dawley rats exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and a binary mixture (PCB 126 + 153) for 14, 31, and 53 wks. Eight adducts were measured to profile oxidative DNA lesions, including 8-oxo-deoxyguanosine (8-oxo-dG), 1,N(6)-ethenodeoxyadenosine (1,N(6)-εdA), N(2),3-ethenoguanine (N(2),3-εG), 1,N(2)-ethenodeoxyguanosine (1,N(2)-εdG), as well as malondialdehyde (M1dG), acrolein (AcrdG), crotonaldehyde (CrdG), and 4-hydroxynonenal-derived dG adducts (HNEdG) by LC-MS/MS analysis. Statistically significant increases were observed for 8-oxo-dG and 1,N(6)-εdA concentrations in hepatic DNA of female rats exposed to the binary mixture (1000 ng/kg/day + 1000 μg/kg/day) but not in rats exposed to PCB 126 (1000 ng/kg/day) or PCB 153 (1000 μg/kg/day) for 14 and 31 wks. However, exposure to PCB 126 (1000 ng/kg/day) for 53 wks significantly increased 8-oxo-dG, 1,N(6)-εdA, AcrdG, and M1dG. Exposure to PCB 153 (1000 μg/kg/day) for 53 wks increased 8-oxo-dG, and 1,N(6)-εdA. Exposure to the binary mixture for 53 wks increased 8-oxo-dG, 1,N(6)-εdA, AcrdG, 1,N(2)-εdG, and N(2),3-εG significantly above control groups. Increased hepatic oxidative DNA adducts following exposure to PCB 126, PCB 153, or the binary mixture shows that an increase in DNA damage may play an important role in hepatic toxicity and carcinogenesis in female Sprague-Dawley rats.

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New method to induce mild traumatic brain injury in rodents produces differential outcomes in female and male Sprague Dawley rats.

Publications

New method to induce mild traumatic brain injury in rodents produces differential outcomes in female and male Sprague Dawley rats.

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