Age-Dependent Differences in Glutathione Peroxidase Activity after Traumatic Brain Injury

Fan, Pichuan; Yamauchi, Toshihiro; Noble, Linda; Ferriero, Donna M.

doi:10.1089/089771503765355513

Cited by 83 publications

(69 citation statements)

References 37 publications

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“…There is ongoing research in experimental TBI to define the age threshold and injury severity that coincides with findings of higher morbidity and mortality. Cognitive and morphological differences have been previously noted in aged experimental brain-injured rats (Fan et al, 2003;Hamm et al, 1991;Hoane et al, 2004;Shah et al, 2006;Shao et al, 2006), and also if injury occurs in the very early stages of development (Casey et al, 2008;Robertson et al, 2007Robertson et al, , 2009Scafidi et al, 2009).…”

Section: Discussionmentioning

confidence: 78%

Age-Related Mitochondrial Changes after Traumatic Brain Injury

Gilmer

Ansari

Roberts

et al. 2010

Journal of Neurotrauma

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Mitochondrial dysfunction is known to occur following traumatic brain injury (TBI) and has been well characterized. This study assessed possible age-related changes in the cortical mitochondrial bioenergetics following TBI. Three hours following a moderate TBI, tissue from the ipsilateral hemisphere (site of impact and penumbra) and the corresponding contralateral region were harvested from young (3-to 5-month-old) and aged (22-to 24-month-old) Fischer 344 rats. Synaptic and extrasynaptic mitochondria were isolated using a Ficoll gradient, and several bioenergetic parameters were examined using a Clark-type electrode. Injury-related respiration deficits were observed in both young and aged rats. Synaptic mitochondria showed an age-related decline in the rate of ATP production, and a decline in respiratory control ratios (RCR), which were not apparent in the extrasynaptic fraction. Following respiration analysis, mitochondrial samples were probed for oxidative damage (3-nitrotyrosine [3-NT], 4-hydroxynonenal [4-HNE], and protein carbonyls [PC]). All markers of oxidative damage were elevated with injury and age in the synaptic fraction, but only with injury in the extrasynaptic fraction. Synaptic mitochondria displayed the highest levels of oxidative damage and may contribute to the synaptic bioenergetic deficits seen following injury. Data indicate that cortical synaptic mitochondria appear to have an increased susceptibility to perturbation with age, suggesting that the increased mitochondrial dysfunction observed following injury may impede recovery in aged animals.

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Section: Discussionmentioning

confidence: 78%

Age-Related Mitochondrial Changes after Traumatic Brain Injury

Gilmer

Ansari

Roberts

et al. 2010

Journal of Neurotrauma

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“…sustained more severe injuries than 4-week-old toddler animals when evaluated 6 h after injury than would have been expected based on brain mass and stiffness. Several researchers have investigated the response of the immature brain in comparison to the adult in rodent (Adelson et al, 2001;Biagas et al, 1996;Fan et al, 2003;Prins et al, 1996) and porcine (Raghupathi and Margulies, 2002) models, highlighting both the vulnerability and plasticity of the immature brain. However, few investigators have explored age-related differences in brain injury response within the pediatric age range (i.e., between infants and toddlers).…”

Section: Discussionmentioning

confidence: 99%

Physiological and Pathological Responses to Head Rotations in Toddler Piglets

Ibrahim

Ralston

Smith

et al. 2010

Journal of Neurotrauma

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Closed head injury is the leading cause of death in children less than 4 years of age, and is thought to be caused in part by rotational inertial motion of the brain. Injury patterns associated with inertial rotations are not well understood in the pediatric population. To characterize the physiological and pathological responses of the immature brain to inertial forces and their relationship to neurological development, toddler-age (4-week-old) piglets were subjected to a single non-impact head rotation at either low (31.6 AE 4.7 rad/sec 2 , n ¼ 4) or moderate (61.0 AE 7.5 rad/sec 2 , n ¼ 6) angular acceleration in the axial direction. Graded outcomes were observed for both physiological and histopathological responses such that increasing angular acceleration and velocity produced more severe responses. Unlike low-acceleration rotations, moderate-acceleration rotations produced marked EEG amplitude suppression immediately post-injury, which remained suppressed for the 6-h survival period. In addition, significantly more severe subarachnoid hemorrhage, ischemia, and axonal injury by b-amyloid precursor protein (b-APP) were observed in moderate-acceleration animals than low-acceleration animals. When compared to infant-age (5-day-old) animals subjected to similar (54.1 AE 9.6 rad/sec 2 ) acceleration rotations, 4-week-old moderate-acceleration animals sustained similar severities of subarachnoid hemorrhage and axonal injury at 6 h post-injury, despite the larger, softer brain in the older piglets. We conclude that the traditional mechanical engineering approach of scaling by brain mass and stiffness cannot explain the vulnerability of the infant brain to acceleration-deceleration movements, compared with the toddler.

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“…65 Although GPx is upregulated in the adult brain after TBI, no such upregulation occurs in the immature brain. 89 Similarly, GPx expression actually decreases in the neonatal brain after hypoxia/ischemia while catalase activity remains unchanged. 78 This inability of the immature brain to respond to injury by upregulating GPx may therefore play a role in the vulnerability of the immature brain to injury.…”

Section: Oxidative Damagementioning

confidence: 98%

Traumatic injury to the immature brain: Inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets

Potts

Koh

Whetstone

et al. 2006

NeuroRX

143

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Summary: Traumatic brain injury (TBI) is the leading cause of morbidity and mortality among children and both clinical and experimental data reveal that the immature brain is unique in its response and vulnerability to TBI compared to the adult brain. Current therapies for pediatric TBI focus on physiologic derangements and are based primarily on adult data. However, it is now evident that secondary biochemical perturbations play an important role in the pathobiology of pediatric TBI and may provide specific therapeutic targets for the treatment of the head-injured child. In this review, we discuss three specific components of the secondary pathogenesis of pediatric TBIinflammation, oxidative injury, and iron-induced damage -and potential therapeutic strategies associated with each. The inflammatory response in the immature brain is more robust than in the adult and characterized by greater disruption of the blood-brain barrier and elaboration of cytokines. The immature brain also has a muted response to oxidative stress compared to the adult due to inadequate expression of certain antioxidant molecules. In addition, the developing brain is less able to detoxify free iron after TBI-induced hemorrhage and cell death. These processes thus provide potential therapeutic targets that may be tailored to pediatric TBI, including anti-inflammatory agents such as minocycline, antioxidants such as glutathione peroxidase, and the iron chelator deferoxamine.

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Age-Dependent Differences in Glutathione Peroxidase Activity after Traumatic Brain Injury

Cited by 83 publications

References 37 publications

Age-Related Mitochondrial Changes after Traumatic Brain Injury

Age-Related Mitochondrial Changes after Traumatic Brain Injury

Physiological and Pathological Responses to Head Rotations in Toddler Piglets

Traumatic injury to the immature brain: Inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets

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