Current concepts of cerebral oxygen transport and energy metabolism after severe traumatic brain injury

Verweij, Bon H.; Amelink, G. J.; Muizelaar, J. Paul

doi:10.1016/s0079-6123(06)61008-x

Cited by 67 publications

(38 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The molecular basis for the reduced aerobic energy metabolism and associated increase in glycolytic lactate production is not completely elucidated [2,3,4]. Oxidative modification and inactivation of one or more mitochondrial metabolic enzymes, and possible impairment of the malate-aspartate shuttle function have been reported [4].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection by Acetyl-<i>L</i>-Carnitine after Traumatic Injury to the Immature Rat Brain

Scafidi

Racz²,

Hazelton³

et al. 2010

Dev Neurosci

110

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in children and is characterized by reduced aerobic cerebral energy metabolism early after injury, possibly due to impaired activity of the pyruvate dehydrogenase complex. Exogenous acetyl-L-carnitine (ALCAR) is metabolized in the brain to acetyl coenzyme A and subsequently enters the tricarboxylic acid cycle. ALCAR administration is neuroprotective in animal models of cerebral ischemia and spinal cord injury, but has not been tested for TBI. This study tested the hypothesis that treatment with ALCAR during the first 24 h following TBI in immature rats improves neurologic outcome and reduces cortical lesion volume. Postnatal day 21–22 male rats were isoflurane anesthetized and used in a controlled cortical impact model of TBI to the left parietal cortex. At 1, 4, 12 and 23 h after injury, rats received ALCAR (100 mg/kg, intraperitoneally) or drug vehicle (normal saline). On days 3–7 after surgery, behavior was assessed using beam walking and novel object recognition tests. On day 7, rats were transcardially perfused and brains were harvested for histological assessment of cortical lesion volume, using stereology. Injured animals displayed a significant increase in foot slips compared to sham-operated rats (6 ± 1 SEM vs. 2 ± 0.2 on day 3 after trauma; n = 7; p < 0.05). The ALCAR-treated rats were not different from shams and had fewer foot slips compared to vehicle-treated animals (2 ± 0.4; n = 7; p< 0.05). The frequency of investigating a novel object for saline-treated TBI animals was reduced compared to shams (45 ± 5% vs. 65 ± 10%; n = 7; p < 0.05), whereas the frequency of investigation for TBI rats treated with ALCAR was not significantly different from that of shams but significantly higher than that of saline-treated TBI rats (68 ± 7; p < 0.05). The left parietal cortical lesion volume, expressed as a percentage of the volume of tissue in the right hemisphere, was significantly smaller in ALCAR-treated than in vehicle-treated TBI rats (14 ± 5% vs. 28 ± 6%; p < 0.05). We conclude that treatment with ALCAR during the first 24 h after TBI improves behavioral outcomes and reduces brain lesion volume in immature rats within the first 7 days after injury.

show abstract

Section: Introductionmentioning

confidence: 99%

Neuroprotection by Acetyl-<i>L</i>-Carnitine after Traumatic Injury to the Immature Rat Brain

Scafidi

Racz²,

Hazelton³

et al. 2010

Dev Neurosci

110

View full text Add to dashboard Cite

show abstract

“…Most studies show that post-traumatic CBF is reduced following focal and diffuse brain damage (Verweij et al, 2007;Werner et al, 2007); however, there is a general understanding that both in humans (Tenjin et al, 1990;Bouma et al, 1991;Bullock et al, 1992;Alexander et al, 1994;Garnett et al, 2001;von Oettingen et al, 2002) and experimental animals (Nilsson et al, 1977;Pollay et al, 1980;Zhuang et al, 1992;Cherian et al, 1994;Bryan, Jr. et al, 1995;Kochanek et al, 1995;Maeda et al, 1997;Hendrich et al, 1999;Liu et al, 2002;Lundblad et al, 2004;Zweckberger et al, 2006) severe reductions of CBF reaching ischemic values are only associated with cortical contusions. The most severe CBF reductions (Ͼ80% of normal CBF) are found in the contused tissue itself (Bouma et al, 1991;Bullock et al, 1992;Alexander et al, 1994;Bryan, Jr. et al, 1995;Kochanek et al, 1995;Schroder et al, 1995;Maeda et al, 1997;Hendrich et al, 1999;Garnett et al, 2001;von Oettingen et al, 2002;Zweckberger et al, 2006) and are observed almost immediately after TBI (Zweckberger et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Changes of Cerebral Blood Flow during the Secondary Expansion of a Cortical Contusion Assessed by¹⁴C-Iodoantipyrine Autoradiography in Mice Using a Non-Invasive Protocol

Engel

Mies

Terpolilli³

et al. 2008

Journal of Neurotrauma

View full text Add to dashboard Cite

Although changes of cerebral blood flow (CBF) in and around traumatic contusions are well documented, the role of CBF for the delayed death of neuronal cells in the traumatic penumbra ultimately resulting in secondary contusion expansion remains unclear. The aim of the current study was therefore to investigate the relationship between changes of CBF and progressive peri-contusional cell death following traumatic brain injury (TBI). CBF and contusion size were measured in C57Bl6 mice under continuous on-line monitoring of (ETp)CO2 before, and at 15 min and 24 h following controlled cortical impact by 14C-iodoantipyrine autoradiography (IAP-AR; n = 5-6 per group) and by Nissl staining, respectively. Contused and ischemic (CBF < 10%) tissue volumes were calculated and compared over time. Cortical CBF in not injured mice varied between 69 and 93 mL/100mg/min depending on the anatomical location. Fifteen minutes after trauma, CBF decreased in the whole brain by approximately 50% (39 +/- 18 mL/100mg/min; p < 0.05), except in contused tissue where it fell by more than 90% (3 +/- 2 mL/100mg/min; p < 0.001). Within 24 h after TBI, CBF recovered to normal values in all brain areas except the contusion where it remained reduced by more than 90% (p < 0.001). Contusion volume expanded from 24.9 to 35.5 mm3 (p < 0.01) from 15 min to 24 h after trauma (+43%), whereas the area of severe ischemia (CBF < 10%) showed only a minimal (+13%) and not significant increase (22.3 to 25.1 mm3). The current data therefore suggest that the delayed secondary expansion of a cortical contusion following traumatic brain injury may not be caused by a reduction of CBF alone.

show abstract

“…Although commonly triggered by ischemia, depressed cerebral metabolism following TBI is a consistent finding that is currently attributed to an initial failure in mitochondrial respiratory function, induced by increased production of reactive oxygen species, ultimately leading to a disruption in calcium homeostasis, and dissipation of mitochondrial transmembrane potential [4,[11][12][13]. The latter, in turn, compromises mitochondrial integrity independent of adequate restoration of CPP and substrates of energy metabolism [14].…”

Section: Discussionmentioning

confidence: 93%

Alterations in Cerebral Oxidative Metabolism following Traumatic Brain Injury

et al. 2011

View full text Add to dashboard Cite

show abstract

Current concepts of cerebral oxygen transport and energy metabolism after severe traumatic brain injury

Cited by 67 publications

References 58 publications

Neuroprotection by Acetyl-<i>L</i>-Carnitine after Traumatic Injury to the Immature Rat Brain

Neuroprotection by Acetyl-<i>L</i>-Carnitine after Traumatic Injury to the Immature Rat Brain

Changes of Cerebral Blood Flow during the Secondary Expansion of a Cortical Contusion Assessed by¹⁴C-Iodoantipyrine Autoradiography in Mice Using a Non-Invasive Protocol

Alterations in Cerebral Oxidative Metabolism following Traumatic Brain Injury

Contact Info

Product

Resources

About

Current concepts of cerebral oxygen transport and energy metabolism after severe traumatic brain injury

Cited by 67 publications

References 58 publications

Neuroprotection by Acetyl-<i>L</i>-Carnitine after Traumatic Injury to the Immature Rat Brain

Neuroprotection by Acetyl-<i>L</i>-Carnitine after Traumatic Injury to the Immature Rat Brain

Changes of Cerebral Blood Flow during the Secondary Expansion of a Cortical Contusion Assessed by14C-Iodoantipyrine Autoradiography in Mice Using a Non-Invasive Protocol

Alterations in Cerebral Oxidative Metabolism following Traumatic Brain Injury

Contact Info

Product

Resources

About

Changes of Cerebral Blood Flow during the Secondary Expansion of a Cortical Contusion Assessed by¹⁴C-Iodoantipyrine Autoradiography in Mice Using a Non-Invasive Protocol