Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Apr;173(2):e73-81.
doi: 10.1016/j.jss.2011.09.056. Epub 2011 Oct 24.

Cardiac reactive oxygen species after traumatic brain injury

Brett E Larson  1 , David W Stockwell, Stefan Boas, Trevor Andrews, George C Wellman, Warren Lockette, Kalev Freeman
Affiliations

Cardiac reactive oxygen species after traumatic brain injury

Brett E Larson et al. J Surg Res. 2012 Apr.

Abstract

Background: Cardiovascular complications after traumatic brain injury (TBI) contribute to morbidity and mortality and may provide a target for therapy. We examined blood pressure and left ventricle contractility after TBI, and tested the hypothesis that β-adrenergic blockade would decrease oxidative stress after TBI.

Material and methods: Rodents received fluid-percussion injury or sham surgery, confirmed with magnetic resonance imaging (MRI) and histopathology. We followed recovery with sensorimotor coordination testing and blood pressure measurements. We assessed left ventricular ejection fraction using ECG-gated cardiac MRI and measured myocardial reactive oxygen species (ROS) with dihydroethidium. We randomized additional TBI and sham animals to postoperative treatment with propranolol or control, for measurement of ROS.

Results: Blood pressure and cardiac contractility were elevated 48 h after TBI. Myocardial tissue sections showed increased ROS. Treatment with propranolol diminished ROS levels following TBI.

Conclusions: TBI is associated with increased cardiac contractility and myocardial ROS; decreased myocardial ROS after β-blockade suggests that sympathetic stimulation is a mechanism of oxidative stress.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A. Neuroimaging with Achieva 3.0T TX magnet after TBI surgery (trauma) or sham surgery (control). Imaging obtained from animals under isofluorane anesthesia 36–48 hours following surgery. Representative sequences are shown with enhancement indicating structural injury (T2-weighted gradient and spin echo [GRaSE]), surrounding edema (fluid-attenuated inversion recovery [FLAIR]) and larger ischemic penumbra (diffusion weighted images [DWI]). B. Neurological function assessment after TBI surgery or sham surgery. Animals were pre-acclimated to the rotarod test, subjected to surgery, and allowed to recover. On the third day after surgery, animals were tested in five consecutive trials to measure length of time on the rotating rod. Values are expressed as mean +/− SEM (control, n = 17; trauma, n=16). *Different from control, two-tailed t test (P < 0.05).
Figure 1
Figure 1
A. Neuroimaging with Achieva 3.0T TX magnet after TBI surgery (trauma) or sham surgery (control). Imaging obtained from animals under isofluorane anesthesia 36–48 hours following surgery. Representative sequences are shown with enhancement indicating structural injury (T2-weighted gradient and spin echo [GRaSE]), surrounding edema (fluid-attenuated inversion recovery [FLAIR]) and larger ischemic penumbra (diffusion weighted images [DWI]). B. Neurological function assessment after TBI surgery or sham surgery. Animals were pre-acclimated to the rotarod test, subjected to surgery, and allowed to recover. On the third day after surgery, animals were tested in five consecutive trials to measure length of time on the rotating rod. Values are expressed as mean +/− SEM (control, n = 17; trauma, n=16). *Different from control, two-tailed t test (P < 0.05).
Figure 2
Figure 2
A. Immunohistochemistry for reactive gliosis after TBI surgery (trauma) or sham surgery (control). Rats were euthanized 7–10 days after surgery for acquisition of ipsilateral cortical tissue adjacent to the area of injury. Confocal microscopy was used to detect fluorescence targeted by an antibody specific to glial fibrillary acidic protein (GFAP) in frozen tissue. Representative slides are shown. B. Graph depicts GFAP fluorescence from cortical tissue sections. At least 3 microscope fields per animal were normalized to background and averaged to determine total area of fluorescence per animal. Values are expressed as mean +/− SEM (control, n = 9; trauma, n=9). *Different from control, two-tailed t test (P < 0.05).
Figure 3
Figure 3
A. Fluid percussion injury measured using high frequency pressure transducer in line with fluid column during procedure. The maximum pressure is shown (49 PSI) over the 500 msec time period. B. Representative tracing of systolic blood pressure after fluid percussion injury (60 second tracing). Intra-operative blood pressure was transduced from the tail artery using an indwelling line placed under anesthesia. The blood pressure increased from 100 mmHg to 153 mmHg over 3 seconds, and then returned to baseline within 30 seconds. B. Blood pressure after TBI surgery (trauma) or sham surgery (control) measured with a non-invasive tail cuff. Representative cuff pressure tracings are shown for control and trauma animals. B. Summary blood pressure data at 2 days after injury. Five to ten readings were taken and averaged for each animal. Values are expressed as mean +/− SEM (control, n=8; trauma, n=8). *Different from control, two-tailed t test (P < 0.05).
Figure 4
Figure 4
A. Cardiac MRI to measure left ventricular ejection fraction (LVEF) after TBI surgery (trauma) or sham surgery (control). Rats recovered from surgery for 2 days and were then placed under isofluorane anesthesia for respiratory and ECG-gated cardiac MRI. LVEF was estimated by determining the average ratio of biplane area of short-axis images of the ventricle in end-systole and end-diastole at three different LV sections (base, mid-LV, and apex) for each animal. Representative images from diastole and systole are shown with the LV cavity highlighted. B. Summary LVEF data. Values are expressed as mean +/− SEM (control, n=4; trauma, n=6). *Different from control, two-tailed t test (P < 0.05).
Figure 5
Figure 5
A. Reactive oxygen species (ROS) in LV myocardium after sham surgery (control, n=12), TBI surgery (trauma, n=12), or TBI surgery followed by treatment with propranolol (trauma + propranolol, n=12). Rats were euthanized 7– 10 days after surgery for acquisition of myocardial tissue and fresh frozen sections were incubated with dihydroethidium (DHE) to determine levels of ROS detected by fluorescence using Zeiss LSM 510 META Laser Scanning Microscope. Negative control slides for each animal were incubated with super oxide dismutase (SOD) immediately prior to addition of DHE (trauma + SOD, n=9). Representative images are shown. B. Graph depicts DHE fluorescence from myocardial tissue sections. Values are expressed as mean +/− SEM *Different from control, ANOVA (P < 0.05).
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Faul MXL, Wald MM, Coronado VG. Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations and Deaths 2002–2006. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; Atlanta (GA): 2010.
    1. Bybee KA, Prasad A. Stress-related cardiomyopathy syndromes. Circulation. 2008 Jul 22;118(4):397–409. - PubMed
    1. Clifton GL, Robertson CS, Kyper K, Taylor AA, Dhekne RD, Grossman RG. Cardiovascular response to severe head injury. Journal of neurosurgery. 1983 Sep;59(3):447–454. - PubMed
    1. Clifton GL, Ziegler MG, Grossman RG. Circulating catecholamines and sympathetic activity after head injury. Neurosurgery. 1981 Jan;8(1):10–14. - PubMed
    1. Robertson CS, Clifton GL, Grossman RG. Oxygen utilization and cardiovascular function in head-injured patients. Neurosurgery. 1984 Sep;15(3):307–314. - PubMed

Publication types

Substances