Peripheral Blood Lymphocytes Mitochondrial Function in Children with Traumatic Brain Injury

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Abstract

Backgraund: It is known that mitochondria play an important role in the mechanisms of brain cells damage and death following traumatic brain injury (TBI). However, the relationship between the severity of brain damage following TBI and mitochondrial dysfunction are not well defined. 

Aim: to study activities of NADN- and succinate dehydrogenases, a key enzyme of mitochondrial oxidative phosphorylation in children with TBI of varying severity and different outcomes; to detect ATP content in lymphocytes; the level of NOx and 3-nitrotyrosine in serum and plasma. 

Methods: all parameters were determined in the dynamics of one month following TBI, and in some cases up to the death of patients. The severity of TBI was scored by Glasgow Coma Scale (GCS), the outcome of TBI — Glasgow Outcome Scale (GOS). Based on the clinical examination children with TBI were divided into 3 groups: (1) mild TBI; (2) severe TBI and (3) severe TBI with fatal outcome. 

Results: we found that activity of dehydrogenases is significantly reduced only in patients with the poor neurologic outcome. The greatest decrease in these parameters was observed in patients with severe traumatic brain injury and fatal outcome. A direct correlation was found between the indices of dehydrogenases activity and ATP content in lymphocytes (r =0.97, p =0.005). The levels of NOx metabolites and 3-nitrotyrosine were significantly increased in children with severe TBI. 

Conclusion: obtained results suggest that mitochondrial dysfunction, impaired cerebral energy metabolism and oxidative stress contribute to cell death in the brain and thus represent therapeutic targets for the treatment of TBI.

About the authors

Rustam Shakirovich Zakirov

Scientific Centre of Children Health

Email: cytochemistry@gmail.com
MD Russian Federation

Elena Gennad'evana Sorokina

Scientific Centre of Children Health

Email: sorokelena@mail.ru
PhD Russian Federation

Ol'ga Vital'evna Karaseva

Institute of Urgent Children Surgery and Traumatology

Email: karaseva.o@list.ru
MD, PhD Russian Federation

Zhanna Borisovna Semenova

Scientific Centre of Children Health; Institute of Urgent Children Surgery and Traumatology

Email: jseman@mail.ru
MD, PhD Russian Federation

Svetlana Valentinovna Petrichuk

Scientific Centre of Children Health

Email: cito@list.ru
PhD, Professor Russian Federation

Leonid Mikhaylovich Roshal'

Scientific Centre of Children Health; Institute of Urgent Children Surgery and Traumatology

Email: lmroshal@mail.ru
MD, PhD, Professor Russian Federation

Vsevolod Grigor'evich Pinelis

Scientific Centre of Children Health

Author for correspondence.
Email: pinelis@mail.ru
MD, PhD, Professor Russian Federation

References

  1. Mendes AA, de Souza LF, Walz R, Dafre A. Perspectives on Molecular Biomarkers of Oxidative Stress and Antioxidant Strategies in Traumatic Brain Injury. Biomed Res Int. 2014;2014:1–18. doi: 10.1155/2014/723060
  2. Потапов АА, Рошаль ЛМ, Лихтерман ЛБ, Кравчук АД. Черепно-мозговая травма: проблемы и перспективы. Вопросы нейрохирургии в институте имени Н.Н. Бурденко. 2009;2:3–8.
  3. Валиуллина СА, Семенова ЖБ, Шарова ЕА. Организационно-экономические и управленческие аспекты оказания медицинской помощи детям с черепно-мозговой травмой. Российский педиатрический журнал. 2010;2б:37–48.
  4. Algattas H, Huanq JH. Traumatic brain injury pathophysiology and treatments: early, intermediate, and late phases post injury. Int J Mol. Sci. 2014;15(1):309–341. doi: 10.3390/ijms15010309
  5. Пинелис ВГ, Сорокина ЕГ. Аутоиммунные механизмы модуляции активности глутаматных рецепторов у детей с эпилепсией и черепно-мозговой травмой. Вестник РАМН. 2008;12:44–51.
  6. Stoica BA, Faden AI. Cell death mechanisms and modulation in traumatic brain injury. Neurotherapeutics. 2010;7(1):3–12. doi: 10.1016/j.nurt.2009.10.023
  7. Xiong Y, Gu Q, Peterson PL, Muizelaar JP, Lee CP. Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury. J Neurotrauma. 1997;14:23–34. doi: 10.1089/neu.1997.14.23
  8. Sullivan PG, Rabchevsky AG, Waldmeier PC, Springer JE. Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal cell death? J Neurosci Res. 2005;79(1–2):231–239. doi: 10.1002/jnr.20292
  9. Robertson CL, Scafidi S, McKenna MC, Fiskum G. Mitochondrial mechanisms of cell death and neuroprotection in pediatric ischemic and traumatic brain injury. Exp Neurol. 2009;218(2):371–380. doi: 10.1016/j.expneurol.2009.04.030
  10. Balan IS, Saladino AJ, Aarabi B, Castellani RJ, Wade C, Stein DM, Eisenberg HM, Chen HH, Fiskum G. Cellular alterations in human traumatic brain injury: changes in mitochondrial morphology reflect regional levels of injury severity. J Neurotrauma. 2013; 30(5):367–381. doi: 10.1089/neu.2012.2339
  11. Vinogradov AD. NADH/NAD+ interaction with NADH: ubiquinone oxidoreductase (complex I). Biochim Biophys Acta. 2008;1777(7–8):729–734. doi: 10.1016/j.bbabio.2008.04.014
  12. Нарциссов РП. Анализ изображения клетки — следующий этап развития клинической цитохимии в педиатрии. Педиатрия. 1998;4:101–105.
  13. Vangilder RL, Rosen CL, Barr TL, Huber JD. Targeting the neurovascular unit for treatment of neurological disorders. Pharmacol Ther. 2011;130(3):239–247. doi: 10.1016/j.pharmthera.2010.12.004
  14. Boldyrev AA, Kazey VI, Leinsoo TA, Mashkina AP, Tyulina OV, Johnson P, Tuneva JO, Chittur S, Carpenter DO. Rodent lymphocytes express functionally active glunamate receptors. Biochem Biophys Res Commun. 2004;324(1):133–139. doi: 10.1016/j.bbrc.2004.09.019
  15. Болдырев АА, Брюшкова ЕА, Владыченская ЕА. NMDA–рецепторы в клетках иммунной системы. Биохимия. 2012;77(2):160–168.
  16. Lifshitz J, Friberg H, Neumar RW, Raghupathi R, Welsh FA, Janmey P, Saatman KE, Wieloch T, Grady MS, McIntosh TK. Structural and functional damage sustained by mitochondria after traumatic brain injury in the rat: evidence for differentially sensitive populations in the cortex and hippocampus. J Cereb Blood Flow Metab. 2003;23(2):219–231. doi: 10.1097/00004647-200302000-00009
  17. Denton RM, Rutter GA, Midgley PJ, McCormack JG. Effects of Ca2+ on reactivities of the calcium-sensitive dehydrogenases within the mitochondria of mammalian tissues. J Cardiovasc Pharmacol. 1988;12(Suppl.5):69–72. doi: 10.1097/00005344-198806125-00012
  18. Сурин АМ, Зобова СН, Тухбатова ГР, Сенилова ЯЕ, Пинелис ВГ, Ходоров БИ. Изменения митохондриального NAD(P)H и нарушения кальциевого гомеостаза в культивируемых нейронах мозжечка крысы при гиперстимуляции глутаматных рецепторов. В сб. материалов международной конференции «Рецепция и внутриклеточная сигнализация». М. 2009. С. 157–162.
  19. Surin AM, Gorbacheva LR, Savinkova IG, Sharipov RR, Khodorov BI, Pinelis VG. Study on ATP concentration changes in cytosol of individual cultured neurons during glutamate-induced deregulation of calcium homeostasis. Biochem (Mosc.). 2014;79(2):146–152. doi: 10.1134/S0006297914020084
  20. Lipton SA, Choi YB, Pan ZH, Lei EZ, Chen HS, Sucher NJ, Loscalzo J, Singel DJ, Stamler JS. A redox based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related compounds. Nature. 1993;364:626–632. doi: 10.1038/364626a0
  21. Nag S, Picard P, Stewart DJ. Expression of nitric oxide synthases and nitrotyrosine during blood-brain barrier breakdown and repair after cold injury. Lab Invest. 2001;81(1):41–49. doi: 10.1038/labinvest.3780210
  22. Bayir H, Kagan VE, Clark RS, Janesko-Feldman K, Rafikov R, Huang Z, Zhang X, Vagni V, Billiar TR, Kochanek PM. Neuronal NOS mediated nitration and inactivation of manganese superoxide dismutase in brain after experimental and human brain injury. J Neurochem. 2007;101(1):168–181. doi: 10.1111/j.1471-4159.2006.04353.x
  23. Brown GC, Borutaite V. Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols. Biochim Biophys Acta. 2004;1658(1–2):44–49. doi: 10.1016/j.bbabio.2004.03.016
  24. Readnower RD, Pandya JD, McEwen ML, Pauly JR, Springer JE, Sullivan PG. Post injury administration of the mitochondrial permeability transition pore inhibitor, NIM811, is neuroprotective and improves cognition after traumatic brain injury in rats. J Neurotrauma. 2011;28(9):1845–1853. doi: 10.1089/neu.2011.1755

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