Unilateral Cortical Contusion Injury in the Rat: Vascular Disruption and Temporal Development of Cortical Necrosis

Sutton, Richard L.; Lescaudron, Laurent; Stein, Donald G.

doi:10.1089/neu.1993.10.135

Cited by 170 publications

(113 citation statements)

References 27 publications

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“…The previously characterized CCI injury device (Sutton et al, 1993;Lindner et al, 1998;Kelly et al, 2000) was used to generate a cortical contusion to the left hemisphere. Each animal was placed under inhalation anesthesia with isoflurane (4% for induction, 2.0% for maintenance, in 100% O 2 at 1.5 l/min).…”

Section: Injurymentioning

confidence: 99%

“…The bone flap was removed and the dura left intact in all animals to receive CCI. An electronically controlled pneumatic piston cylinder (Hydraulics Control Inc., Emeryville, CA, USA) mounted onto a stereotaxic micromanipulator (Kopf Instruments, Tujunga, CA, USA) was used to allow for precise localization and control of the impact (Sutton et al, 1993). The piston cylinder was angled 19° away from vertical to allow the flat (5 mm diameter) impactor tip to make contact perpendicular to the brain's surface.…”

mentioning

confidence: 99%

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Voluntary exercise or amphetamine treatment, but not the combination, increases hippocampal brain-derived neurotrophic factor and synapsin I following cortical contusion injury in rats

et al. 2008

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Prior work has shown that d-amphetamine (AMPH) treatment or voluntary exercise improves cognitive functions after traumatic brain injury (TBI). In addition, voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF). The current study was conducted to determine how AMPH and exercise treatments, either alone or in combination, affect molecular events that may underlie recovery following controlled cortical impact (CCI) injury in rats. We also determined if these treatments reduced injury-induced oxidative stress. Following a CCI or sham injury, rats received AMPH (1 mg/kg/day) or saline treatment via an ALZET ® pump and were housed with or without access to a running wheel for 7 days. CCI rats ran significantly less than sham controls, but exercise level was not altered by drug treatment. On day 7 the hippocampus ipsilateral to injury was harvested and BDNF, synapsin I and phosphorylated (P) -synapsin I proteins were quantified. Exercise or AMPH alone significantly increased BDNF protein in sham and CCI rats, but this effect was lost with the combined treatment. In sham-injured rats synapsin I increased significantly after AMPH or exercise, but did not increase after combined treatment. Synapsin levels, including the Psynapsin/total synapsin ratio, were reduced from sham controls in the saline-treated CCI groups, with or without exercise. AMPH treatment significantly increased the P-synapsin/total synapsin ratio after CCI, an effect that was attenuated by combining AMPH with exercise. Exercise or AMPH treatment alone significantly decreased hippocampal carbonyl groups on oxidized proteins in the CCI rats, compared with saline-treated sedentary counterparts, but this reduction in a marker of oxidative stress was not found with the combination of exercise and AMPH treatment. These results indicate that, whereas exercise or AMPH treatment alone may induce plasticity and reduce oxidative stress after TBI, combining these treatments may cancel each other's therapeutic effects. Keywordscontrolled cortical impact; norepinephrine; oxidized proteins; running wheel; traumatic brain injury *Corresponding author. Tel: +1-310-825-1904; fax: +1-310-794-2147. E-mail address: ggriesbach@mednet.ucla.edu (G. S. Griesbach). 1 G.S.G. and R.L.S. contributed equally to this work. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 June 27. Published in final edited form as:Neuroscience. 2008 June 23; 154(2): 530-540. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptTraumatic brain injury (TBI) continues to be one of the leading causes of mortality and morbidity, with approximately 5.3 million Americans suffering from enduring disabilities resulting from TBI (Binder et al., 2005). Despite many experimental and clinical efforts using numerous therapeutic approaches, there are currently no proven treatments to alleviate the sequelae of TBI or to enhance recovery of function.Our laboratories have been investigating treatment strategies that may faci...

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Section: Injurymentioning

confidence: 99%

mentioning

confidence: 99%

Voluntary exercise or amphetamine treatment, but not the combination, increases hippocampal brain-derived neurotrophic factor and synapsin I following cortical contusion injury in rats

et al. 2008

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“…The previously characterized CCI injury model (Dixon et al 1991;Sutton et al 1993) was used to generate a focal TBI to the left hemisphere. Following a midline incision, the skull was exposed and a 6-mm diameter craniotomy was drilled over the left hemisphere under a microscope, centered at ) 4 mm anteriorposterior (AP), 5 mm midlateral (ML) relative to bregma.…”

Section: Injurymentioning

confidence: 99%

Increased cerebral uptake and oxidation of exogenous βHB improves ATP following traumatic brain injury in adult rats

Prins

Lee

Fujima

et al. 2004

Journal of Neurochemistry

101

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There is growing evidence of the brain's ability to increase its reliance on alternative metabolic substrates under conditions of energy stress such as starvation, hypoxia and ischemia. We hypothesized that following traumatic brain injury (TBI), which results in immediate changes in energy metabolism, the adult brain increases uptake and oxidation of the alternative substrate b-hydroxybutyrate (bHB). Arterio-venous differences were used to determine global cerebral uptake of bHB and production of 14 CO 2 from [ 14 C]3-bHB 3 h after controlled cortical impact (CCI) injury. Quantitative bioluminescence was used to assess regional changes in ATP concentration. As expected, adult sham and CCI animals with only endogenously available bHB showed no significant increase in cerebral uptake of bHB or 14 CO 2 production. Increasing arterial bHB concentrations 2.9-fold with 3 h of bHB infusion failed to increase cerebral uptake of bHB or 14 CO 2 production in adult sham animals. Only CCI animals that received a 3-h bHB infusion showed an 8.5-fold increase in cerebral uptake of bHB and greater than 10.7-fold increase in 14 CO 2 production relative to sham bHB-infused animals. The TBI-induced 20% decrease in ipsilateral cortical ATP concentration was alleviated by 3 h of bHB infusion beginning immediately after CCI injury. Keywords: alternative substrates, b-hydroxybutyrate, metabolism, traumatic brain injury. Although glucose remains the primary cerebral metabolic substrate under normal conditions, there are many physiological states during which the brain's reliance on glucose shifts to alternative substrates (Owen et al. 1967;Hawkins et al. 1971;Dahlquist and Persson 1976;Kries and Ross 1992;Vannucci and Vannucci 2000). In vitro studies have documented uptake and oxidation of 14 C-labeled glycerol (McKenna et al. 1986a) (Edmond et al. 1987). However, ketone bodies such as bHB are the only endogenously circulating alternative substrates that have been shown significantly to supplement cerebral metabolism (Owen et al. 1967;Hawkins et al. 1971;Dahlquist and Persson 1976). In normally fed adult mammals bHB metabolism comprises less than 3% of total cerebral metabolism and bHB is present in low circulating concentrations (0.1 mM) with negligible uptake into the brain (Hawkins et al. 1971). However, upon increasing bHB arterial concentrations by starvation for 2 days or more, cerebral uptake is significantly enhanced (Hawkins et al. 1971). Increased cerebral uptake of bHB has also been shown during development (Hawkins et al. 1971;Dahlquist and Persson 1976), following starvation (Owen et al. 1967) and in diabetes (Kries and Ross 1992). The brain's ability to increase its reliance on bHB appears to be a common form of cerebral metabolic adaptation under conditions of insufficient glucose availability and developmental increases in cerebral energy demand.The evidence for the use of bHB by the brain under conditions of cerebral metabolic stress suggests a role for this alternative substrate in cerebral metabolism after ...

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“…In contusion brain injuries, rapid local brain deformation causes cell shearing and membrane rupture, resulting in irreversible cell injury and necrosis of affected tissues [7,8]. In penumbral regions where cells undergo delayed neurodegeneration, other mechanisms can dominate, including apoptosis, which is a programmed cell death cascade regulated by effector proteins and caspase protease activation [9,10], and autophagy, which is the lysosomal degradation of components within the cell [11][12][13].…”

Section: Regulation Of Cell Deathmentioning

confidence: 99%

Genetic Manipulation of Cell Death and Neuroplasticity Pathways in Traumatic Brain Injury

2012

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Traumatic brain injury (TBI) initiates a complex cascade of secondary neurodegenerative mechanisms contributing to cell dysfunction and necrotic and apoptotic cell death. The injured brain responds by activating endogenous reparative processes to counter the neurodegeneration or remodel the brain to enhance functional recovery. A vast array of genetically altered mice provide a unique opportunity to target single genes or proteins to better understand their role in cell death and endogenous repair after TBI. Among the earliest targets for transgenic and knockout studies in TBI have been programmed cell death mediators, such as the Bcl-2 family of proteins, caspases, and caspaseindependent pathways. In addition, the role of cell cycle regulatory elements in the posttraumatic cell death pathway has been explored in mouse models. As interest grows in neuroplasticity in TBI, the use of transgenic and knockout mice in studies focused on gliogenesis, neurogenesis, and the balance of growth-promoting and growth-inhibiting molecules has increased in recent years. With proper consideration of potential effects of constitutive gene alteration, traditional transgenic and knockout models can provide valuable insights into TBI pathobiology. Through increasing sophistication of conditional and cell-type specific genetic manipulations, TBI studies in genetically altered mice will be increasingly useful for identification and validation of novel therapeutic targets.

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Unilateral Cortical Contusion Injury in the Rat: Vascular Disruption and Temporal Development of Cortical Necrosis

Cited by 170 publications

References 27 publications

Voluntary exercise or amphetamine treatment, but not the combination, increases hippocampal brain-derived neurotrophic factor and synapsin I following cortical contusion injury in rats

Voluntary exercise or amphetamine treatment, but not the combination, increases hippocampal brain-derived neurotrophic factor and synapsin I following cortical contusion injury in rats

Increased cerebral uptake and oxidation of exogenous βHB improves ATP following traumatic brain injury in adult rats

Genetic Manipulation of Cell Death and Neuroplasticity Pathways in Traumatic Brain Injury

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