Abstract
Impaired cerebral energy metabolism may be a major contributor to the secondary injury cascade that occurs following traumatic brain injury (TBI). To estimate the cortical energy metabolic state following mild and severe controlled cortical contusion (CCC) TBI in rats, ipsi-and contralateral cortical tissues were frozen in situ at 15 and 40 min post-injury and adenylate (ATP, ADP, AMP) levels were analyzed using high-performance liquid chromatography (HPLC) and the energy charge (EC) was calculated. At 15 min post-injury, mildly brain-injured animals showed a 43% decrease in cortical ATP levels and a 2.4-fold increase in AMP levels (P < 0.05), and there was a significant reduction of the ipsilateral cortical EC when compared to sham-injured animals (P < 0.05). At 40 min post-injury, the ipsilateral adenylate levels and EC had recovered to the values observed in the sham-injury group. In the severe CCC group, there was a 51% decrease in ipsilateral cortical ATP levels and a 5.3-fold increase in AMP levels with a significant reduction of cortical EC at 15 min post-injury (P < 0.05). At 40 min post-injury, a 2.6-fold ipsilateral increase in AMP levels and an 11% and 44% decrease in EC and ATP levels, respectively, remained (P < 0.05). A 37–38% reduction of the total adenylate pool was observed ipsilaterally in both CCC severity groups at the early time-point, and a 19% and 28% decrease remained in the mild and severe CCC groups, respectively, at 40 min post-injury. Significant contralateral ATP and EC changes were only observed in the severe CCC group at 40 min post-injury (P < 0.05). The energy-requiring secondary injury cascades that occur early post-injury do not challenge the brain tissue to the extent of ATP depletion and may provide a window of opportunity for therapeutic intervention.
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Acknowledgments
Mr. Åke Eriksson for the HPLC analysis of adenylates. Ms Ulla Carlsson for good technical skills and assistance. Professor Urban Pontén for valuable suggestions on the in situ freezing technique. This study was supported by The Swedish Medical Research Council (project no 7888), the Laerdal Foundation for Acute Medicine, the Selander Foundation, the 1987 Foundation for Stroke Research, The Åhlén Foundation and King Gustav V and Queen Victoria’s Foundation.
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Marklund, N., Salci, K., Ronquist, G. et al. Energy Metabolic Changes in the Early Post-injury Period Following Traumatic Brain Injury in Rats. Neurochem Res 31, 1085–1093 (2006). https://doi.org/10.1007/s11064-006-9120-0
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DOI: https://doi.org/10.1007/s11064-006-9120-0