rmtОбщая реаниматологияGeneral Reanimatology1813-97792411-7110FSBI "SRIGR" RAMS10.15360/1813-9779-2009-5-80rmt-542Research ArticleОБЗОРЫ И КРАТКИЕ СООБЩЕНИЯREVIEWS & SHORT COMMUNICATIONSРоль оксида азота в повреждении нейронов при критических состоянияхRole of Nitric Oxide in Neuronal Damages in Critical ConditionsКиселеваА.В.KiselevaA. V.-ЧурляевЮ. А.ChurlyaevYu. A.-ГригорьевЕ. В.GrigoryevYe. V.grigorievev@mailru20092010200955Том V № 5 2009 г.8080Copyright © Киселева А.V., Чурляев Ю.А., Григорьев Е.В., 20092009Киселева А., Чурляев Ю.А., Григорьев Е.В.Kiseleva A.V., Churlyaev Y.A., Grigoryev Y.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.reanimatology.com/rmt/article/view/542

Представленный литературный обзор включает в себя современные положения о роли оксида азота и его метаболизма в развитии энцефалопатий у больных в критическом состоянии. Описаны механизмы участия оксида азота в нейроток-сичности, индукции апоптоза нейронов, варианты участия оксида азота в развитии ишемии головного мозга, очаговом повреждении головного мозга при тяжелой черепно-мозговой травме. Дается краткий обзор экспериментально обоснованных методов терапии, направленных на коррекцию повреждения нейронов, опосредованных оксидом азота (модуляция синтеза оксида азота, антиоксиданты). Ключевые слова: ишемия головного мозга, травматические повреждения головного мозга, оксид азота, варианты синтазы оксида азота, нейротоксичность, апоптоз, пути коррекции.

The presented review of literature covers the current notions of the role of nitric oxide and its metabolism in the development of encephalopathies in critically ill patients. The mechanisms of nitric oxide involvement in neurotoxicity, neuronal induction of apoptosis, and the types of nitric oxide involvement in the development of brain ischemia, focal cerebral damage in severe brain injury are described. A concise review of the experimentally founded therapy options aimed at correcting nitric oxide-induced neuronal damage (modulation of nitric oxide synthesis, antioxidants) is given. Key words: brain ischemia, brain traumatic injuries, nitric oxide synthase variants, neurotoxicity, apoptosis, correction modes.

ReferencesLam A. A., Hyland K., Heales S. J.Lam A. A., Hyland K., Heales S. J.Morris S. M.Arginine metabolism in vascular biology and disease. Vasc. Med. 2005; 10 (Suppl 1): 83—87.Morris S. M.Arginine metabolism in vascular biology and disease. Vasc. Med. 2005; 10 (Suppl 1): 83—87.Brave S. R., Tucker J. F., Gibson A. et al.Localization of nitric oxide syn-thase within non-adrenergic, non-cholinergic nerves in the mouse anococcygeus. Neurosci Lett. 1993; 161 (1): 93—96.Brave S. R., Tucker J. F., Gibson A. et al.Localization of nitric oxide syn-thase within non-adrenergic, non-cholinergic nerves in the mouse anococcygeus. Neurosci Lett. 1993; 161 (1): 93—96.Викторов И. В.Роль оксида азота и других свободных радикалов в ишемической патологии мозга. Вестник РАМН 2000; 4: 5—10.Викторов И. В.Роль оксида азота и других свободных радикалов в ишемической патологии мозга. Вестник РАМН 2000; 4: 5—10.Метельская В. А., Гуманова Н. Г.Оксид азота: роль в регуляции биологических реакций, методы определения в крови человека. Лабораторная медицина 2005; 7: 19—24.Метельская В. А., Гуманова Н. Г.Оксид азота: роль в регуляции биологических реакций, методы определения в крови человека. Лабораторная медицина 2005; 7: 19—24.Alam M. S., Akaike T., Okamoto S. et al.Role of nitric oxide in host defense in murine Salmonellosis as a function of its antibacterial and antiapoptotic activities. Infect. Immun. 2002; 70 (6): 3130—3142.Alam M. S., Akaike T., Okamoto S. et al.Role of nitric oxide in host defense in murine Salmonellosis as a function of its antibacterial and antiapoptotic activities. Infect. Immun. 2002; 70 (6): 3130—3142.Thippeswamy T., McKay J. S., Quinn J. P., Morris R.Nitric oxide, a biological double-faced janus-is this good or bad? Histol Histopathol. 2006; 21 (4): 445—458.Thippeswamy T., McKay J. S., Quinn J. P., Morris R.Nitric oxide, a biological double-faced janus-is this good or bad? Histol Histopathol. 2006; 21 (4): 445—458.Choi B. M., Pae H. O., Jang S. I. et al.Nitric oxide as a Pro-apoptotic as well as Anti-apoptotic Modulator. J. Bioch. Mol. Biol. 2002; 35 (1): 116—126.Choi B. M., Pae H. O., Jang S. I. et al.Nitric oxide as a Pro-apoptotic as well as Anti-apoptotic Modulator. J. Bioch. Mol. Biol. 2002; 35 (1): 116—126.Sobey C. G., Faraci F. M.Subarachnoid haemorrhage: what happens to the cerebral arteries? Clin. Exp. Pharmacol. Physiol. 1998; 25 (11): 867—876.Sobey C. G., Faraci F. M.Subarachnoid haemorrhage: what happens to the cerebral arteries? Clin. Exp. Pharmacol. Physiol. 1998; 25 (11): 867—876.Pacher P., Beckman J. S., Liaudet L.Nitric oxide and peroxynitrite in health and disease. Physiol. Rev. 2007; 87 (1): 315—424.Pacher P., Beckman J. S., Liaudet L.Nitric oxide and peroxynitrite in health and disease. Physiol. Rev. 2007; 87 (1): 315—424.Alvarez B., Radi R.Peroxynitrite reactivity with amino acids and proteins. Amino Acids 2003; 25 (3—4): 295—3Alvarez B., Radi R.Peroxynitrite reactivity with amino acids and proteins. Amino Acids 2003; 25 (3—4): 295—3Reiter T. A.NO chemistry: a diversity of targets in the cell. Redox Rep. 2006; 11 (5): 194—206.Reiter T. A.NO chemistry: a diversity of targets in the cell. Redox Rep. 2006; 11 (5): 194—206.Szabo C.Multiple pathways of peroxynitrite cytotoxicity. Toxicol Lett. 2003; 140—141: 105—112.Szabo C.Multiple pathways of peroxynitrite cytotoxicity. Toxicol Lett. 2003; 140—141: 105—112.Abe K., Pan L. H., Watanabe M. et al.Upregulation of protein-tyrosine nitration in the anterior horn cells of amyotrophic lateral sclerosis. Neurol. Res. 1997; 19 (2): 124—128.Abe K., Pan L. H., Watanabe M. et al.Upregulation of protein-tyrosine nitration in the anterior horn cells of amyotrophic lateral sclerosis. Neurol. Res. 1997; 19 (2): 124—128.Nieminen A. L.Apoptosis and necrosis in health and disease: role of mitochondria. Int Rev Cytol. 2003; 224: 29—55.Nieminen A. L.Apoptosis and necrosis in health and disease: role of mitochondria. Int Rev Cytol. 2003; 224: 29—55.Kim Y. M., Chung H. T., Simmons R. L., Billiar T. R.Cellular non-heme iron content is a determinant of nitric oxide-mediated apoptosis, necrosis and caspase inhibition. J.Biol.Chem. 2000; 275 (15): 10954—10961.Kim Y. M., Chung H. T., Simmons R. L., Billiar T. R.Cellular non-heme iron content is a determinant of nitric oxide-mediated apoptosis, necrosis and caspase inhibition. J.Biol.Chem. 2000; 275 (15): 10954—10961.Chen J., Qin J., Liu X. et al.Nitric oxide-mediated neuronal apoptosis in rats with recurrent febrile seizures through endoplasmic reticulum stress pathway. Neurosci. Lett. 2008; 443 (3): 134—139.Chen J., Qin J., Liu X. et al.Nitric oxide-mediated neuronal apoptosis in rats with recurrent febrile seizures through endoplasmic reticulum stress pathway. Neurosci. Lett. 2008; 443 (3): 134—139.Perrotta C., De Palma C., Clementi E.Nitric oxide and sphingolipids: mechanisms of interaction and role in cellular pathophysiology. Biol. Chem. 2008; 389 (11): 1391—1397.Perrotta C., De Palma C., Clementi E.Nitric oxide and sphingolipids: mechanisms of interaction and role in cellular pathophysiology. Biol. Chem. 2008; 389 (11): 1391—1397.Peng Z. F., Chen M. J., Yap Y. W. et al.Proteasome inhibition: an early or late event in nitric oxide-induced neuronal death? Nitric Oxide. 2008; 18 (2): 136—145.Peng Z. F., Chen M. J., Yap Y. W. et al.Proteasome inhibition: an early or late event in nitric oxide-induced neuronal death? Nitric Oxide. 2008; 18 (2): 136—145.Perez-Rodriguez R., Fuentes M. P., Olivan A. M. et al.Mechanisms of nitric oxide-induced apoptosis in bovine chromaffin cells: Role of mitochondria and apoptotic proteins. J Neurosci Res. 2007; 85 (10): 2224—2238.Perez-Rodriguez R., Fuentes M. P., Olivan A. M. et al.Mechanisms of nitric oxide-induced apoptosis in bovine chromaffin cells: Role of mitochondria and apoptotic proteins. J Neurosci Res. 2007; 85 (10): 2224—2238.Kim Y. M., Chung H. T., Kim S. S. et al.Nitric oxide protects PC12 cells from serum deprivation-induced apoptosis by cGMP-dependent inhibition of caspase signaling. J. Neurosci. 1999; 19 (16): 6740—6747.Kim Y. M., Chung H. T., Kim S. S. et al.Nitric oxide protects PC12 cells from serum deprivation-induced apoptosis by cGMP-dependent inhibition of caspase signaling. J. Neurosci. 1999; 19 (16): 6740—6747.Kim P. K., Kwon Y. G., Chung H. T., Kim Y. M.Regulation of caspases by nitric oxide. Ann. N. Y. Acad. Sci. 2002; 962: 42—52.Kim P. K., Kwon Y. G., Chung H. T., Kim Y. M.Regulation of caspases by nitric oxide. Ann. N. Y. Acad. Sci. 2002; 962: 42—52.Bobba A., Atlante A., Moro L. et al.Nitric oxide has dual opposite roles during early and late phases of apoptosis in cerebellar granule neurons. Apoptosis 2007; 12 (9): 1597—1610.Bobba A., Atlante A., Moro L. et al.Nitric oxide has dual opposite roles during early and late phases of apoptosis in cerebellar granule neurons. Apoptosis 2007; 12 (9): 1597—1610.Chung H. T., Choi B. M., Kwon Y. G., Kim Y. M.Interactive relations between nitric oxide (NO) and carbon monoxide (CO): heme oxyge-nase-1/CO pathway is a key modulator in NO-mediated antiapoptosis and anti-inflammation. Methods Enzymol. 2008; 441: 329—338.Chung H. T., Choi B. M., Kwon Y. G., Kim Y. M.Interactive relations between nitric oxide (NO) and carbon monoxide (CO): heme oxyge-nase-1/CO pathway is a key modulator in NO-mediated antiapoptosis and anti-inflammation. Methods Enzymol. 2008; 441: 329—338.Guix F. X., Uribesalgo I., Coma M., Munoz F. J.The physiology and pathophysiology of nitric oxide in the brain. Prog. Neurobiol. 2005; 76 (2): 126—152.Guix F. X., Uribesalgo I., Coma M., Munoz F. J.The physiology and pathophysiology of nitric oxide in the brain. Prog. Neurobiol. 2005; 76 (2): 126—152.BolanosJ. P., Almeida A.Roles of nitric oxide in brain hypoxia-ischemia. Biochim. Biophys. Acta 1999; 1411 (2—3): 415—436.BolanosJ. P., Almeida A.Roles of nitric oxide in brain hypoxia-ischemia. Biochim. Biophys. Acta 1999; 1411 (2—3): 415—436.Grandati M., Verrecchia C., Revaud M. L. et al.Calcium-independent NO-synthase activity and nitrites/nitrates production in transient focal cerebral ischemia in mice. Br. J. Pharmacol. 1997; 122 (4): 625—630.Grandati M., Verrecchia C., Revaud M. L. et al.Calcium-independent NO-synthase activity and nitrites/nitrates production in transient focal cerebral ischemia in mice. Br. J. Pharmacol. 1997; 122 (4): 625—630.Moro M. A., Cardenas A., Hurtado O. et al.Role of nitric oxide after brain ischemia. Cell Calcium 2004; 36 (3—4): 265—275.Moro M. A., Cardenas A., Hurtado O. et al.Role of nitric oxide after brain ischemia. Cell Calcium 2004; 36 (3—4): 265—275.Salom J. B., Orti M., Centeno J. M. et al.Reduction of infarct size by the NO donors sodium nitroprusside and spermine/NO after transient focal cerebral ischemia in rats. Brain Res. 2000; 865 (2): 149—156.Salom J. B., Orti M., Centeno J. M. et al.Reduction of infarct size by the NO donors sodium nitroprusside and spermine/NO after transient focal cerebral ischemia in rats. Brain Res. 2000; 865 (2): 149—156.Endres M., Laufs U., Liao J. K., Moskowitz M. A.Targeting eNOS for stroke protection. Trends Neurosci. 2004; 27 (5): 283—289.Endres M., Laufs U., Liao J. K., Moskowitz M. A.Targeting eNOS for stroke protection. Trends Neurosci. 2004; 27 (5): 283—289.Sironi L., Cimino M., Guerrini U. et al.Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage. Arterioscler. Thromb. Vasc. Biol. 2003; 23 (2): 322—327.Sironi L., Cimino M., Guerrini U. et al.Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage. Arterioscler. Thromb. Vasc. Biol. 2003; 23 (2): 322—327.Hafezi-Moghadam A., Simoncini T., Yang Z. et al.Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase. Nat. Med. 2002; 8 (5): 473—479.Hafezi-Moghadam A., Simoncini T., Yang Z. et al.Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase. Nat. Med. 2002; 8 (5): 473—479.Willmot M., Gray L., Gibson C. et al.A systematic review of nitric oxide donors and L-arginine in experimental stroke; effects on infarct size and cerebral blood flow. Nitric Oxide 2005; 12 (3): 141 — 149.Willmot M., Gray L., Gibson C. et al.A systematic review of nitric oxide donors and L-arginine in experimental stroke; effects on infarct size and cerebral blood flow. Nitric Oxide 2005; 12 (3): 141 — 149.Willmot M., Gibson C., Gray L. et al.Nitric oxide synthase inhibitors in experimental ischemic stroke and their effects on infarct size and cerebral blood flow: a systematic review. Free Radic. Biol. Med. 2005; 39 (3): 412—425.Willmot M., Gibson C., Gray L. et al.Nitric oxide synthase inhibitors in experimental ischemic stroke and their effects on infarct size and cerebral blood flow: a systematic review. Free Radic. Biol. Med. 2005; 39 (3): 412—425.Wong D., Dorovini-Zis K., Vincent S. R.Cytokines, nitric oxide, and CGMP modulate the permeability of an in vitro model of the human blood-brain barrier. Exp. Neurol. 2004; 190 (2): 446—455.Wong D., Dorovini-Zis K., Vincent S. R.Cytokines, nitric oxide, and CGMP modulate the permeability of an in vitro model of the human blood-brain barrier. Exp. Neurol. 2004; 190 (2): 446—455.Vasquez-Vivar J, Kalyanaraman B., Martasek P. et al.Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc. Natl. Acad. Sci. USA 1998; 95 (16): 9220—9225.Vasquez-Vivar J, Kalyanaraman B., Martasek P. et al.Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc. Natl. Acad. Sci. USA 1998; 95 (16): 9220—9225.Xie Z., Wei M., Morgan T. E. et al.Peroxynitrite mediates neurotoxicity of amyloid beta-peptide1-42- and lipopolysaccharide-activated microglia. J. Neurosci. 2002; 22 (9): 3484—3492.Xie Z., Wei M., Morgan T. E. et al.Peroxynitrite mediates neurotoxicity of amyloid beta-peptide1-42- and lipopolysaccharide-activated microglia. J. Neurosci. 2002; 22 (9): 3484—3492.Pignitter M., Gorren A. C., Nedeianu S. et al.Inefficient spin trapping of superoxide in the presence of nitric-oxide: implications for studies on nitric-oxide synthase uncoupling. Free Radic. Biol. Med. 2006; 41 (3): 455—463.Pignitter M., Gorren A. C., Nedeianu S. et al.Inefficient spin trapping of superoxide in the presence of nitric-oxide: implications for studies on nitric-oxide synthase uncoupling. Free Radic. Biol. Med. 2006; 41 (3): 455—463.Alderton W. K., Cooper C. E., Knowles R. G.Nitric oxide synthases: structure, function and inhibition. Biochem. J. 2001; 357 (Pt 3): 593—615.Alderton W. K., Cooper C. E., Knowles R. G.Nitric oxide synthases: structure, function and inhibition. Biochem. J. 2001; 357 (Pt 3): 593—615.Gentleman S. M., Leclercq P. D., Moyes L. et al.Long-term intracerebral inflammatory response after traumatic brain injury. Forensic. Sci. Int. 2004; 146 (2—3): 97—104.Gentleman S. M., Leclercq P. D., Moyes L. et al.Long-term intracerebral inflammatory response after traumatic brain injury. Forensic. Sci. Int. 2004; 146 (2—3): 97—104.Wang Y. B., Ou S. W., Li G. Y. et al.Concentrations of nitric oxide in rat brain tissues after diffuse brain injury and neuroprotection by the selective inducible nitric oxide synthase inhibitor aminoguanidine. Chin. Med. Sci. J. 2005; 20 (3): 222.Wang Y. B., Ou S. W., Li G. Y. et al.Concentrations of nitric oxide in rat brain tissues after diffuse brain injury and neuroprotection by the selective inducible nitric oxide synthase inhibitor aminoguanidine. Chin. Med. Sci. J. 2005; 20 (3): 222.Thiel V. E., Audus K. L.Nitric oxide and blood-brain barrier integrity Antioxid. Redox Signal 2001; 3 (2): 273—278.Thiel V. E., Audus K. L.Nitric oxide and blood-brain barrier integrity Antioxid. Redox Signal 2001; 3 (2): 273—278.Unterberg A. W., Stover J, Kress B., Kiening K. L.Edema and brain trauma. Neuroscience 2004; 129 (4): 1021—1029.Unterberg A. W., Stover J, Kress B., Kiening K. L.Edema and brain trauma. Neuroscience 2004; 129 (4): 1021—1029.Yamauchi A., Dohgu S., Nishioku T. et al.An inhibitory role of nitric oxide in the dynamic regulation of the blood-brain barrier function. Cell Mol. Neurobiol. 2007; 27 (3): 263—270.Yamauchi A., Dohgu S., Nishioku T. et al.An inhibitory role of nitric oxide in the dynamic regulation of the blood-brain barrier function. Cell Mol. Neurobiol. 2007; 27 (3): 263—270.Mayhan W. G.Inhibition of nitric oxide synthase does not alter basal permeability of the blood-brain barrier. Brain Res. 2000; 855 (1): 143—149.Mayhan W. G.Inhibition of nitric oxide synthase does not alter basal permeability of the blood-brain barrier. Brain Res. 2000; 855 (1): 143—149.Sharma H. S., Drieu K., Alm P., WestmanJ.Role of nitric oxide in blood-brain barrier permeability, brain edema and cell damage following hyperthermic brain injury. An experimental study using EGB-761 and Gingkolide B pre-treatment in the rat. Acta Neurochir. Suppl. 2000; 76: 81—86.Sharma H. S., Drieu K., Alm P., WestmanJ.Role of nitric oxide in blood-brain barrier permeability, brain edema and cell damage following hyperthermic brain injury. An experimental study using EGB-761 and Gingkolide B pre-treatment in the rat. Acta Neurochir. Suppl. 2000; 76: 81—86.Deng Y., Thompson B. M., Gao X., Hall E. D.Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury. Exp. Neurol. 2007; 205 (1): 154—165.Deng Y., Thompson B. M., Gao X., Hall E. D.Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury. Exp. Neurol. 2007; 205 (1): 154—165.Singh I. N., Sullivan P. G., Deng Y. et al.Time course of post-traumatic mitochondrial oxidative damage and dysfunction in a mouse model of focal traumatic brain injury: implications for neuroprotective therapy. J. Cereb. Blood Flow Metab. 2006; 26 (11): 1407—1418.Singh I. N., Sullivan P. G., Deng Y. et al.Time course of post-traumatic mitochondrial oxidative damage and dysfunction in a mouse model of focal traumatic brain injury: implications for neuroprotective therapy. J. Cereb. Blood Flow Metab. 2006; 26 (11): 1407—1418.Darwish R. S., Amiridze N., Aarabi B.Nitrotyrosine as an oxidative stress marker: evidence for involvement in neurologic outcome in human traumatic brain injury. J. Trauma. 2007; 63 (2): 439—442.Darwish R. S., Amiridze N., Aarabi B.Nitrotyrosine as an oxidative stress marker: evidence for involvement in neurologic outcome in human traumatic brain injury. J. Trauma. 2007; 63 (2): 439—442.Delwing D., Delwing D., Bavaresco C. S., Wyse A. T.Protective effect of nitric oxide synthase inhibition or antioxidants on brain oxidative damage caused by intracerebroventricular arginine administration. Brain Res. 2008; 1193: 120—127.Delwing D., Delwing D., Bavaresco C. S., Wyse A. T.Protective effect of nitric oxide synthase inhibition or antioxidants on brain oxidative damage caused by intracerebroventricular arginine administration. Brain Res. 2008; 1193: 120—127.Hall E. D., Detloff M. R., Johnson K., Kupina N. C.Peroxynitrite-medi-ated protein nitration and lipid peroxidation in a mouse model of traumatic brain injury. J. Neurotrauma 2004; 21 (1): 9—20.Hall E. D., Detloff M. R., Johnson K., Kupina N. C.Peroxynitrite-medi-ated protein nitration and lipid peroxidation in a mouse model of traumatic brain injury. J. Neurotrauma 2004; 21 (1): 9—20.Szaby C., Ischiropoulos H., Radi R.Peroxynitrite: biochemistry, patho-physiology and development of therapeutics. Nat. Rev. Drug Discov. 2007; 6 (8): 662—680.Szaby C., Ischiropoulos H., Radi R.Peroxynitrite: biochemistry, patho-physiology and development of therapeutics. Nat. Rev. Drug Discov. 2007; 6 (8): 662—680.Sharma H. S., Wiklund L., Badgaiyan R. D. et al.Intracerebral administration of neuronal nitric oxide synthase antiserum attenuates traumatic brain injury-induced blood-brain barrier permeability, brain edema formation, and sensory motor disturbances in the rat. Acta Neurochir. Suppl. 2006; 96: 288—294.Sharma H. S., Wiklund L., Badgaiyan R. D. et al.Intracerebral administration of neuronal nitric oxide synthase antiserum attenuates traumatic brain injury-induced blood-brain barrier permeability, brain edema formation, and sensory motor disturbances in the rat. Acta Neurochir. Suppl. 2006; 96: 288—294.Boveri M., Kinsner A., Berezowski V. et al.Highly purified lipoteichoic acid from gram-positive bacteria inducesin vitroblood-brain barrier disruption through glia activation: role of pro-inflammatory cytokines and nitric oxide. Neuroscience 2006; 137 (4): 1193—1209.Boveri M., Kinsner A., Berezowski V. et al.Highly purified lipoteichoic acid from gram-positive bacteria inducesin vitroblood-brain barrier disruption through glia activation: role of pro-inflammatory cytokines and nitric oxide. Neuroscience 2006; 137 (4): 1193—1209.Gahm C., Holmin S., Wiklund P. N. et al.Neuroprotection by selective inhibition of inducible nitric oxide synthase after experimental brain contusion. J. Neurotrauma 2006; 23 (9): 1343—1354.Gahm C., Holmin S., Wiklund P. N. et al.Neuroprotection by selective inhibition of inducible nitric oxide synthase after experimental brain contusion. J. Neurotrauma 2006; 23 (9): 1343—1354.Louin G., Marchand-Verrecchia C., Palmier B. et al.Selective inhibition of inducible nitric oxide synthase reduces neurological deficit but not cerebral edema following traumatic brain injury. Neuropharmacology 2006; 50 (2): 182—190.Louin G., Marchand-Verrecchia C., Palmier B. et al.Selective inhibition of inducible nitric oxide synthase reduces neurological deficit but not cerebral edema following traumatic brain injury. Neuropharmacology 2006; 50 (2): 182—190.Foley L. M., Hitchens T. K., Melick J. A. et al.Effect of inducible nitric oxide synthase on cerebral blood flow after experimental traumatic brain injury in mice. J. Neurotrauma 2008; 25 (4): 299—310.Foley L. M., Hitchens T. K., Melick J. A. et al.Effect of inducible nitric oxide synthase on cerebral blood flow after experimental traumatic brain injury in mice. J. Neurotrauma 2008; 25 (4): 299—310.Huttemann M., Lee I., Kreipke C. W., Petrov T.Suppression of the inducible form of nitric oxide synthase prior to traumatic brain injury improves cytochrome c oxidase activity and normalizes cellular energy levels. Neuroscience 2008; 151 (1): 148—154.Huttemann M., Lee I., Kreipke C. W., Petrov T.Suppression of the inducible form of nitric oxide synthase prior to traumatic brain injury improves cytochrome c oxidase activity and normalizes cellular energy levels. Neuroscience 2008; 151 (1): 148—154.Winter S., Konter J., Scheler S. et al.Permeability changes in response to NONOate and NONOate prodrug derived nitric oxide in a blood-brain barrier model formed by primary porcine endothelial cells. Nitric Oxide 2008; 18 (3): 229—239.Winter S., Konter J., Scheler S. et al.Permeability changes in response to NONOate and NONOate prodrug derived nitric oxide in a blood-brain barrier model formed by primary porcine endothelial cells. Nitric Oxide 2008; 18 (3): 229—239.Cherian L., Hlatky R., Robertson C. S.Nitric oxide in traumatic brain injury. Brain Pathol. 2004; 14 (2): 195—201.Cherian L., Hlatky R., Robertson C. S.Nitric oxide in traumatic brain injury. Brain Pathol. 2004; 14 (2): 195—201.

The authors declare that there are no conflicts of interest present.