Acute etomidate treatment reduces cognitive deficits and histopathology in rats with traumatic brain injury

Dixon, C. Edward; Ma, Xiecheng; Kline, Anthony E.; Yan, Hong; Ferimer, Howard; Kochanek, Patrick M.; Wisniewski, Stephen R.; Jenkins, Larry W.; Marion, Donald W.

doi:10.1097/01.ccm.0000080493.04978.73

Cited by 32 publications

(17 citation statements)

References 40 publications

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“…The impactor tip was leveled with the surface of the brain, and the injury was administered (impact speed: 4 m/sec, injury depth: 2.6 mm, dwell time: 50 msec). The injury settings were consistent with previous studies and designed to generate a brain injury with reproducible motor and cognitive deficits, as well as underlying cortical and hippocampal tissue loss (Dixon et al, 1991(Dixon et al, , 2003. Following injury the anesthesia was stopped, the incision was closed with interrupted silk sutures, and the animals were ventilated on 100% oxygen until spontaneous return of respiration, at which point the endotracheal tube was removed.…”

Section: Traumatic Brain Injurymentioning

confidence: 82%

“…Neuronal counting in the selectively vulnerable CA1 and CA3 regions of the dorsal hippocampus underlying the area of the contusion was also performed using coronal sections 3.5 mm posterior to the bregma (Dixon et al, 1999b(Dixon et al, , 2003. The pyramidal cell layer from CA1 to the dentate gyrus of each hippocampus was sequentially imaged using a 10Âobjective (Nikon), digitally reconstructed into a montage (ImageJ), and the CA1 and CA3 subfields were identified.…”

Section: Tissue Analysesmentioning

confidence: 99%

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Resveratrol Attenuates Behavioral Impairments and Reduces Cortical and Hippocampal Loss in a Rat Controlled Cortical Impact Model of Traumatic Brain Injury

Singleton

Yan

Fellows-Mayle

et al. 2010

Journal of Neurotrauma

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117

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Resveratrol (3,5,4 0 -trihydroxystilbene) is a plant-derived small molecule that is protective against multiple neurological and systemic insults. To date, no studies have explored the potential for resveratrol to provide behavioral protection in adult animals in the setting of traumatic brain injury (TBI). Using 50 male Sprague-Dawley rats, we employed the controlled cortical impact (CCI) model to ascertain whether post-injury administration of resveratrol would reduce the severity of the well-described cognitive and motor deficits associated with the model. Contusion volumes and hippocampal neuronal numbers were also measured to characterize the tissue and neuronal-sparing properties, respectively, of resveratrol. We found that 100 mg/kg, but not 10 mg/kg, of intraperitoneal resveratrol administered after injury provides significant behavioral protection in rats sustaining CCI. Specifically, rodents treated with 100 mg/kg of resveratrol showed improvements in motor performance (beam balance and beam walking) and testing of visuospatial memory (Morris water maze). Behavioral protection was correlated with significantly reduced contusion volumes, preservation of CA1 and CA3 hippocampal neurons, and protection from overt hippocampal loss as a result of incorporation into the overlying cortical contusion in resveratrol-treated animals. Although the mechanisms by which resveratrol mediates its neuroprotection is unclear, the current study adds to the growing literature identifying resveratrol as a potential therapy for human brain injury.

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Section: Traumatic Brain Injurymentioning

confidence: 82%

Section: Tissue Analysesmentioning

confidence: 99%

Resveratrol Attenuates Behavioral Impairments and Reduces Cortical and Hippocampal Loss in a Rat Controlled Cortical Impact Model of Traumatic Brain Injury

Singleton

Yan

Fellows-Mayle

et al. 2010

Journal of Neurotrauma

Self Cite

117

View full text Add to dashboard Cite

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“…In contrast, there are numerous rodent models of acute and chronic degenerative diseases in the young and mature brain, in which standardized and sensitive behavioral outcome measures have been successfully correlated with regional neuropathology due in large part, to an extensive literature in rodent behavioral neuroscience (Almli 2000,Bona 1997,Dixon 2003,Young 1986). Research in swine behavior is historically limited to veterinary science communities, with a focus on neuro-development rather than neuropathology.…”

Section: Introductionmentioning

confidence: 99%

Neurobehavioral functional deficits following closed head injury in the neonatal pig

Friess

Ichord

Owens

et al. 2007

Experimental Neurology

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Neurobehavioral deficits in higher cortical systems have not been described previously in a large animal model of diffuse brain injury. Anesthetized 3-5 day old piglets were subjected to either mild (142 rad/sec) or moderate (188 rad/sec) rapid non-impact axial rotations of the head. Multiple domains of cortical function were evaluated 5 times during the 12 day post-injury period using tests of neurobehavioral function devised for piglets. There were no observed differences in neurobehavioral outcomes between mild injury pigs (N = 8) and instrumented shams (N = 4). Moderately injured piglets (N = 7) had significantly lower interest in exploring their environment and had higher failure rates in visual-based problem solving compared to instrumented shams (N = 5) on Day 1 and 4 after injury. Neurobehavioral functional deficits correlated with neuropathologic damage in the neonatal pigs after inertial head injury. Injured axons detected by immunohistochemistry (β-APP) were absent in mild injury and sham piglets, but were observed in moderately injured piglet brains. In summary, we have developed a quantitative battery of neurobehavioral functional assessments for large animals that correlate with neuropathologic axonal damage and may have wide applications in the fields of cardiac resuscitation, stroke, and hypoxicischemic brain injury.

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“…Several groups have reported a treatment-related improvement in learning and/or memory after experimental TBI in conjunction with CA3 neuronal survival (Sanderson et al, 1999, Leoni et al, 2000, Kline et al, 2001, Philips et al, 2001, Floyd et al, 2002, Kline et al, 2002, Ozdemir et al, 2005, Statler et al, 2006. However, other reports have clearly documented learning deficits in brain-injured animals in the absence of discernable hippocampal damage (Lyeth et al, 1990) or the converse, an improvement in MWM performance after injury without CA3 neuroprotection (Dixon et al, 2003, Hoover et al, 2004.…”

Section: Discussionmentioning

confidence: 95%

Neurotrophin-mediated neuroprotection of hippocampal neurons following traumatic brain injury is not associated with acute recovery of hippocampal function

et al. 2007

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Traumatic brain injury (TBI) causes selective hippocampal cell death which is believed to be associated with the cognitive impairment observed in both clinical and experimental settings. The endogenous neurotrophin NT-4/5, a TrkB ligand, has been shown to be neuroprotective for vulnerable CA3 pyramidal neurons after experimental brain injury. In this study, infusion of recombinant NT-4/5 increased survival of CA2/3 pyramidal neurons to 71% after lateral fluid percussion injury in rats, compared to 55% in vehicle-treated controls. The functional outcome of this NT-4/5-mediated neuroprotection was examined using three hippocampal-dependent behavioral tests. Injury-induced impairment was evident in all three tests, but interestingly, there was no treatment-related improvement in any of these measures. Similarly, injury-induced decreased excitability in the Schaffer collaterals was not affected by NT-4/5 treatment. We propose that a deeper understanding of the factors that link neuronal survival to recovery of function will be important for future studies of potentially therapeutic agents.

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Acute etomidate treatment reduces cognitive deficits and histopathology in rats with traumatic brain injury

Cited by 32 publications

References 40 publications

Resveratrol Attenuates Behavioral Impairments and Reduces Cortical and Hippocampal Loss in a Rat Controlled Cortical Impact Model of Traumatic Brain Injury

Resveratrol Attenuates Behavioral Impairments and Reduces Cortical and Hippocampal Loss in a Rat Controlled Cortical Impact Model of Traumatic Brain Injury

Neurobehavioral functional deficits following closed head injury in the neonatal pig

Neurotrophin-mediated neuroprotection of hippocampal neurons following traumatic brain injury is not associated with acute recovery of hippocampal function

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