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Seizure-related Brain Injuries in Organophosphate Poisoning

Hur, Gyeung-Haeng  
  • 초록

    The features of seizure-related brain injuries in rats poisoned i.p. with diisopropylfiuorophosphate were investigated. Pyridostigmine bromide (0.1 mg/kg) and atropine methylnitrate (20 mg/kg), which are centrally inactive, were pretreated i.m. 30 min and 10 min, respectively. before diisopropylfluorophosphate (10 mg /kg, $2LD_50$ ) poisoning to reduce the mortality and eliminate peripheral signs. Diisopropylfluorophosphate induced severe limbic seizures, and early necrotic and delayed apoptotic brain injuries. The necrotic brain injury, which was closely related to seizure intensity, was exerted as early as 1 hr predominently in hippocampus and piriform cortex. showing spongiform change (malacia) of neurophils in severe cases, in contrast to a typical apoptotic (TUNEL-positive)pattern after 12 hr in thalamus, and a mixed type in amygdala. Nitric oxide content in cerebrospinal fiuid significantly increased after 2 hr, reaching a maximal level at 6 hr. Pretreatment with $_L-N^G$ -nitroarginine, an inhibitor of nitric oxide synthase, reduced nitric oxide content and attenuated only apoptotic brain injury in all four brain regions examined without affecting seizure intensity and necrotic injury. Taken together, early necrotic and delayed apoptotic brain injuries induced by diisopropylfiuorophosphate poisoning in rats may be related to seizure intensity and nitric oxide production, respectively.


  • 주제어

    Organophosphates .   Seizures .   Brain injuries .   Nitric oxide .   Apoptosis.  

  • 참고문헌 (45)

    1. Chondrocyte apoptosis induced by nitric oxide , Blanco, F.J.;Ochs, R.L.;Schwartz, H.;Lotz, M. , Am. J. Pathol. / v.146,pp.75-85,
    2. Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures , Dawson, V.L.;Dawson, T.M.;London, E.D.;Bredt, D.S. , Proc. Natl. Acad. Sci. USA / v.88,pp.6368-6371,
    3. Nitric oxide induces apoptosis in mouse thymocytes , Fehsel, K.;Kroncke, K.-D.;Meyer, K.L.;Huber, H.;Wahn, V.;Kolb-Bachofen, V. , J. Immunol. / v.155,pp.2858-2865,
    4. Apoptosis in splenic B lymphocytes , Illera, V.A.;Perandones, C.E.;Stunz, L.L.;Mower, D.A.Jr.;Ashman, R.F. , J. Immunol. / v.151,pp.2965-2973,
    5. Role of NO production in NMDA receptor-mediated neurotransmitter release in cerebral cortex , Montague, P.R.;Gancayco, C.D.;Winn, M.J.;Marchase, R.B.;Fieldlander, M.J. , Science / v.263,pp.973-977,
    6. Seizure-related brain damage induced by cholinergic agents , Olney, J.W.;de Gubareff, T.;Labruyere, J. , Nature / v.301,pp.520-522,
    7. Evidence of apoptotic cell death after experimental traumatic brain injury in the rat , Rink, A.;Fung, K.-M.;Trojanowski, J.Q.;Lee, V.M.-Y.;Neugebauer, E.;McIntosh, T.K. , Am. J. Pathol. / v.147,pp.1575-1583,
    8. Nitric oxide synthase induces macrophage death by apoptosis , Sarih, M.;Souvannavong, V.;Adam, A. , Biochem. Biophys. Res. Comm. / v.191,pp.503-508,
    9. Anticonvulsants for poisoning by the organophosphorus compound soman : pharmacological mechanisms , Shih, T.-M.;Koviak, T.A.;Capricio, B.R. , Neurosci. Biobehav. Rev. / v.15,pp.349-362,
    10. Histochemical mapping of nitric oxide synthase in the rat brain , Vincent, S.R.;Kimura, H. , Neuroscience / v.46,pp.755-784,
    11. Reactive astrocytes express NADPH-diaphorase in vivo after transient ischemia , Endoh, M.;Maiese, K.;Pulsinelli, W.A.;Wagner, J.A. , Neurosci. Lett. / v.154,pp.125-128,
    12. Kainate-induced apoptosis cell death in hippocampal neurons , Pollard, H.;Charriaut-Marlangue, C.;Cantagrel, S.;Represa, A.;Robain, O.;Moreau, J.;Ben-Ari, Y. , Neuroscience / v.63,pp.7-18,
    13. Apoptosis and necrosis after reversible focal ischemia : an in situ DNA fragmentation analysis , Charriaut-Marlangue, C.;Margaill, I.;Represa, A.;Popovici, T.;Plotkine, M.;Ben-Ari, Y. , J. Cereb. Blood Flow Metab. / v.16,pp.186-194,
    14. Nitric oxide in cells , Lancaster, J.R., Jr. , Am. Scientist / v.80,pp.248-259,
    15. Apoptosis in the pathogenesis and treatment of disease , Thompson, C.B. , Science / v.267,pp.1456-1462,
    16. Organophosphate-induced brain induries : delayed apoptosis mediated by nitric oxide , Kim, Y.-B.;Hur, K.-H.;Shin, S.;Kang, J.-K.;Sok, D.-E. , Neuroscience / v.,pp.,
    17. NMDA-dependent superoxide production and neurotoxicity , Lafon-Cazal, M.;Pietri, S.;Culcasi, M.;Bockaert, J. , Nature / v.363,pp.535-537,
    18. Paradoxical facilitation of pilocarpine-induced seizures in the mouse by MK-801 and the nitric oxide inhibitor$_L$-NAME , Starr, M.S.;Starr, B.S. , Pharmacol. Biochem. Behav. / v.45,pp.321-325,
    19. Apoptosis and necrosis : two distinct events induced, respectively, by mild and intense insults with N-methyl-$_p$-aspartate or nitric oxide/superoxide in cortical cultures , Bonfoco, E.;Krainc, D.;Ankarcrona, M.;Nicotera, P.;Lipton, S.A. , Proc. Natl. Acad. Sci. USA / v.92,pp.7162-7166,
    20. Effects of soman-induced seizures on different extracellular amino acid levels and glutamate uptake in rat hippocampus , Lallement, G.;Carpentier, P.;Collet, A.;Pernot-Marino, I.;Baubichon, D.;Blanchet, G. , Brain Res. / v.563,pp.234-240,
    21. Histomorphogenesis of soman-induced encephalocardiomyopathy in Sprague-Dawley rats , Tryphonas, L.;Clement, J.G. , Toxicol. Pathol. / v.23,pp.393-409,
    22. Protection against nerve agent-induced neuropathology, but not cardiac pathology, is associated with the anticonvulsant action of drug treatment , McDonough, J.H., Jr.;Dochterman, L.W.;Smith, C.D.;Shih, T.-M. , Neurotoxicology / v.15,pp.123-132,
    23. Increase in IL-6, IL-1 and TNF levels in rat brain following traumatic lesion , Taupin, V.;Toulmond, S.;Serrano, A.;Benevides, J.;Zavala, F. , J. Neuroimmunol / v.42,pp.177-186,
    24. Microtubule-associated protein 2 (MAP-2) : a sensitive marker of seizure-related brain damage , Ballough, G.P.H.;Martin, L.J.;Cann, F.J.;Graham, J.S.;Smith, C.D.;Kling, C.E.;Forster, J.S.;Phann, S.;Filbert, M.G. , J. Neurosci. Meth. / v.61,pp.23-32,
    25. Internucleosomal DNA cleavage involved in ischemia-induced neuronal death , Okamoto, M.;Matsumoto, M.;Chtsuki, T.;Taguchi, A.;Mikoshiba, K.;Yanagihara, T.;Kamada, T. , Biochem. Biophys. Res. Comm. / v.196,pp.1356-1362,
    26. Suppression of adjuvant-induced arthritis by selective inhibition of inducible nitric oxide synthase , Connor, J.R.;Manning, P.T.;Settle, S.L.;Moore, W.M.;Jerome, G.M.;Webber, R.K.;Tjoeng, F.S.;Currie M.G. , Eur. J. Pharmacol. / v.273,pp.15-24,
    27. Selective potentiation of NMDA-induced neuronal injury following induction of astrocytic iNOS , Hewett, S.J.;Csernansky, C.A.;Choi, D.W. , Neuron / v.13,pp.487-494,
    28. Neurotoxicity of excitatory amino acid receptor agonists in young rat hippocampal slices , Garthwaite, G.;Garthwaite, J. , J. Neurosci. Meth. / v.29,pp.33-42,
    29. NMDA receptor activation produces concurrent generation of nitric oxide and reactive oxygen species : implication for cell death , Gunasekar, P.G.;Kanthasamy, A.G.;Borowitz, J.L.;Isom, G.E. , J. Neurochem. / v.65,pp.2016-2021,
    30. Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by soman , Sparenborg, S.;Brennecke, L.H.;Jaax, N.K.;Braitman, D.J. , Neuropharmacology / v.31,pp.357-368,
    31. The role of nitric oxide in soman-induced seizures, neuropathology, and lethality , Lallement, G.;Shih, T.-M.;Pernot-Marino, I.;Baubichon, D.;Foquin, A.;McDonough, J.H., Jr. , Pharmacol. Biochem. Behav. / v.54,pp.731-737,
    32. Glutamateinduced neuronal death is not a programmed cell death in cerebellar culture , Dessi, F.;Charriaut-Marlangue, C.;Khrestchatisky, M.;Ben-Ari, Y. , J. Neurochem. / v.60,pp.1953-1955,
    33. Nerve cell death induced in vivo by kainic acid and quinolinic acid does not involve apoptosis , Ignatowicz, E.;Vezzani, A.-M.;Rizzi, M.;D'Incalci, M. , Neuroreport / v.2,pp.651-654,
    34. Nitric oxide synthase generates superoxide and nitric oxide in argininedepleted cells leading to peroxynitrite-mediated cellular injury , Xia, Y.;Dawson, V.L.;Dawson, T.M.;Snyder, S.H.;Zweier, J.L. , Proc. Natl. Acad. Sci. USA / v.93,pp.6770-6774,
    35. Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures , Dawson, V.L.;Dawson, T.M.;Bartley, D.A.;Uhl, G.R.;Snyder, S.H. , J. Neurosci. / v.13,pp.2651-2661,
    36. Tacrine-induced seizure and brain damage in LiCl-treated rats can be prevented by $N^w$-nitro-Larginine methyl ester , Bagetta, G.;Iannone, M.;Scorsa, A.M.;Nistico, G. , Eur. J. Pharmacol. / v.213,pp.301-304,
    37. Nitric oxide-mediated mitochondrial damage in the brain : mechanisms and implications for neurodegenerative diseases , Bolanos, J.P.;Almeida, A.;Stewart, V.;Peuchen, S.;Land, J.M.;Clark, J.B.;Heales, S.J.R. , J. Neurochem. / v.68,pp.2227-2240,
    38. $_L$-Arginine potentiates excitatory amino acid-induced seizures elicited in the deep prepiriform cortex , De Sarro, G.;Di Paola, E.D.;De Sarro, A.;Vidal, M.J. , Eur. J. Pharmacol. / v.230,pp.151-158,
    39. Glutamate triggers internucleosomal DNA cleavage in neuronal cells , Kure, S.;Tominaga, T.;Yoshimoto, T.;Tada, K.;Narisawa, K. , Biochem. Biophys. Res. Comm. / v.179-,pp.39-45,
    40. The nitric oxide-cyclic GMP signalling pathway in rat brain , Southam, E.;Garthwaite, J. , Neuropharmacology / v.32,pp.1267-1277,
    41. Glutamate-induced neuronal death : a succession of necrosis and apoptosis depending on mitochondrial function , Ankarcrona, M.;Dypbukt, J.M.;Bonfoco, E.;Zhivotovsky, B.;Orrenius, S.;Lipton, S.A.;Nicotera, P. , Neuron / v.15,pp.961-973,
    42. Direct microinjection of soman or ⅤⅩ into the amygdala produces repetitive limbic convulsions and neuropathology , McDnough, J.H., Jr.;McLeod, C.G., Jr.;Nipwoda, M.T. , Brain Res. / v.435,pp.123-137,
    43. A role of nitric oxide in organophosphate-induced convulsions , Kim, Y.-B.;Hur, K.-H.;Lee, Y.-S.;Han, B.-G.;Shin, S. , Environ. Toxicol. Pharmacol. / v.3,pp.53-56,
    44. Glutamate neurotoxicity in cortical cell culture , Choi, D.W.;Maulucci-Gedde, M.;Kriegstein, A.R. , J. Neurosci. / v.7,pp.357-368,
    45. Apparent hydroxy1 radical production by peroxynitrite : implications for endothelial injury from nitric oxide and superoxide , Beckman, J.S.;Beckman, T.W.;Chen, J.;Marshall, P.A.;Freeman, B.A. , Proc. Natl. Acad. Sci. USA / v.87,pp.1620-1624,

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