Summary
The role of nitric oxide (NO) in traumatic brain injury (TBI)-induced sensory motor function and brain pathology was examined using intracerebral administration of neuronal nitric oxide synthase (nNOS) antiserum in a rat model. TBI was produced by a making a longitudinal incision into the right parietal cerebral cortex limited to the dorsal surface of the hippocampus. Focal TBI induces profound edematous swelling, extravasation of Evans blue dye, and up-regulation of nNOS in the injured cerebral cortex and the underlying subcortical areas at 5 hours. The traumatized animals exhibited pronounced sensory motor deficit, as seen using Rota-Rod and grid-walking tests. Intracerebral administration of nNOS antiserum (1 : 20) 5 minutes and 1 hour after TBI significantly attenuated brain edema formation, Evans blue leakage, and nNOS expression in the injured cortex and the underlying subcortical regions. The nNOS antiserum-treated rats showed improved sensory motor functions. However, administration of nNOS antiserum 2 hours after TBI did not influence these parameters significantly. These novel observations suggest that NO participates in blood-brain barrier disruption, edema formation, and sensory motor disturbances in the early phase of TBI, and that nNOS antiserum has some potential therapeutic value requiring additional investigation.
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Ahn MJ, Sherwood ER, Prough DS, Lin CY, DeWitt DS (2004) The effects of traumatic brain injury on cerebral blood flow and brain tissue nitric oxide levels and cytokine expression. J Neurotrauma 21: 1431–1442
Bayir H, Kagan VE, Borisenko GG, Tyurina YY, Janesko KL, Vagni VA, Billiar TR, Williams DL, Kochanek PM (2005) Enhanced oxidative stress in iNOS-deficient mice after traumatic brain injury: support for a neuroprotective role of iNOS. J Cereb Blood Flow Metab 25: 673–684
Calingasan NY, Park LC, Calo LL, Trifiletti RR, Gandy SE, Gibson GE (1998) Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism. Am J Pathol 153: 599–610
Cipolla MJ, Crete R, Vitullo L, Rix RD (2004) Transcellular transport as a mechanism of blood-brain barrier disruption during stroke. Front Biosci 9: 777–785
Dey PK, Sharma HS (1983) Ambient temperature and development of traumatic brain oedema in anaesthetized animals. Indian J Med Res 77: 554–563
Dey PK, Sharma HS (1984) Influence of ambient temperature and drug treatments on brain oedema induced by impact injury on skull in rats. Indian J Physiol Pharmacol 28: 177–186
Hooper DC, Scott GS, Zborek A, Mikheeva T, Kean RB, Koprowski H, Spitsin SV (2000) Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. FASEB J 14: 691–698
Hurst RD, Clark JB (1997) Nitric oxide-induced blood-brain barrier dysfunction is not mediated by inhibition of mitochondrial respiratory chain activity and/or energy depletion. Nitric Oxide 1: 121–129
Hurst RD, Azam S, Hurst A, Clark JB (2001) Nitric-oxide-induced inhibition of glyceraldehyde-3-phosphate dehydrogenase may mediate reduced endothelial cell monolayer integrity in an in vitro model blood-brain barrier. Brain Res 894: 181–188
Jaworowicz DJ Jr, Korytko PJ, Singh Lakhman S, Boje KM (1998) Nitric oxide and prostaglandin E2 formation parallels blood-brain barrier disruption in an experimental rat model of bacterial meningitis. Brain Res Bull 46: 541–546
Martinez-Lara E, Canuelo AR, Siles E, Hernandez R, Del Moral ML, Blanco S, Pedrosa JA, Rodrigo J, Peinado MA (2005) Constitutive nitric oxide synthases are responsible for the nitric oxide production in the ischemic aged cerebral cortex. Brain Res 1054: 88–94
Mayhan WG (1995) Role of nitric oxide in disruption of the blood-brain barrier during acute hypertension. Brain Res 686: 99–103
Munoz-Fernandez MA, Fresno M (1998) The role of tumour necrosis factor, interleukin 6, interferon-gamma and inducible nitric oxide synthase in the development and pathology of the nervous system. Prog Neurobiol 56: 307–340
Park EM, Cho S, Frys KA, Glickstein SB, Zhou P, Anrather J, Ross ME, Iadecola C (2005) Inducible nitric oxide synthase contributes to gender differences in ischemic brain injury. J Cereb Blood Flow Metab [Epub ahead of print]
Sharma HS (2005) Pathophysiology of blood-spinal cord barrier in traumatic injury and repair. Curr Pharm Des 11: 1353–1389
Sharma HS (2005) Alterations of amino acid neurotransmitters in hyperthermic brain injury. J Neural Transm [in press]
Sharma HS, Alm P (2002) Nitric oxide synthase inhibitors influence dynorphin A (1–17) immunoreactivity in the rat brain following hyperthermia. Amino Acids 23: 247–259
Sharma HS, Winkler T (2002) Assessment of spinal cord pathology following trauma using spinal cord evoked potentials: a pharmacological and morphological study in the rat. Muscle Nerve [Suppl] 11: S83–S91
Sharma HS, Alm P (2004) Role of nitric oxide on the blood-brain and the spinal cord barriers. In: Sharma HS, Westman J (eds) Blood-spinal cord and brain barriers in health and disease. Elsevier Academic Press, San Diego, pp 191–230
Sharma HS, Westman J (2004) Blood-spinal cord and brain barriers in health and disease. Academic Press, San Diego, pp 1–617
Sharma HS, Cervós-Navarro J, Gosztonyi G, Dey PK (1992) Role of serotonin in traumatic brain injury. An experimental study in the rat. In: Globus M, Dietrich WD (eds) The role of neurotransmitters in brain injury. Plenum Press, New York, pp 147–152
Sharma HS, Westman J, Olsson Y, Alm P (1996) Involvement of nitric oxide in acute spinal cord injury: an immunocytochemical study using light and electron microscopy in the rat. Neurosci Res 24: 373–384
Sharma HS, Nyberg F, Gordh T, Alm P, Westman J (1997) Topical application of insulin like growth factor-1 reduces edema and upregulation of neuronal nitric oxide synthase following trauma to the rat spinal cord. Acta Neurochir [Suppl] 70: 130–133
Sharma HS, Westman J, Alm P, Sjoquist PO, Cervos-Navarro J, Nyberg F (1997) Involvement of nitric oxide in the pathophysiology of acute heat stress in the rat. Influence of a new antioxidant compound H-290/51. Ann NY Acad Sci 813: 581–590
Sharma HS, Alm P, Westman J (1998) Nitric oxide and carbon monoxide in the brain pathology of heat stress. Prog Brain Res 115: 297–333
Sharma HS, Nyberg F, Westman J, Alm P, Gordh T, Lindholm D (1998) Brain derived neurotrophic factor and insulin like growth factor-1 attenuate upregulation of nitric oxide synthase and cell injury following trauma to the spinal cord. An immunohistochemical study in the rat. Amino Acids 14: 121–129
Sharma HS, Nyberg F, Gordh T, Alm P, Westman J (1998) Neurotrophic factors attenuate neuronal nitric oxide synthase upregulation, microvascular permeability disturbances, edema formation and cell injury in the spinal cord following trauma. In: Stålberg E, Sharma HS, Olsson Y (eds) Spinal cord monitoring: basic principles, regeneration, pathophysiology, and clinical aspects. Springer, New York, pp 118–148
Sharma HS, Drieu K, Alm P, Westman J (2000) 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 pretreatment in the rat. Acta Neurochir [Suppl] 76: 81–86
Sharma HS, Winkler T, Stalberg E, Mohanty S, Westman J (2000) p-Chlorophenylalanine, an inhibitor of serotonin synthesis reduces blood-brain barrier permeability, cerebral blood flow, edema formation and cell injury following trauma to the rat brain. Acta Neurochir [Suppl] 76: 91–95
Sharma HS, Sjoquist PO, Alm P (2003) A new antioxidant compound H-290151 attenuates spinal cord injury induced expression of constitutive and inducible isoforms of nitric oxide synthase and edema formation in the rat. Acta Neurochir [Suppl] 86: 415–420
Sharma HS, Winkler T, Stalberg E, Gordh T, Alm P, Westman J (2003) Topical application of TNF-alpha antiserum attenuates spinal cord trauma induced edema formation, microvascular permeability disturbances and cell injury in the rat. Acta Neurochir [Suppl] 86: 407–413
Sharma HS, Badgaiyan RD, Mohanty S, Alm P, Wiklund L (2005) Neuroprotective effects of nitric oxide synthase inhibitors in spinal cord injury induced pathophysiology and motor functions. An experimental study in the rat. Ann NY Acad Sci 1053: 422–434
Tan KH, Harrington S, Purcell WM, Hurst RD (2004) Peroxynitrite mediates nitric oxide-induced blood-brain barrier damage. Neurochem Res 29: 579–587
Warner DS, Sheng H, Batinic-Haberle I (2004) Oxidants, antioxidants and the ischemic brain. J Exp Biol 207: 3221–3231
Zhou P, Qian L, Iadecola C (2005) Nitric oxide inhibits caspase activation and apoptotic morphology but does not rescue neuronal death. J Cereb Blood Flow Metab 25: 348–357
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Sharma, H.S., Wiklund, L., Badgaiyan, R.D., Mohanty, S., Alm, P. (2006). 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. In: Hoff, J.T., Keep, R.F., Xi, G., Hua, Y. (eds) Brain Edema XIII. Acta Neurochirurgica Supplementum, vol 96. Springer, Vienna. https://doi.org/10.1007/3-211-30714-1_62
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DOI: https://doi.org/10.1007/3-211-30714-1_62
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