Contribution of polyamine oxidase to brain injury after trauma

View More View Less
  • 1 Department of Neurological Surgery, University of Wisconsin and Veterans Administration Hospital, Madison, Wisconsin; and Department of Neurological Surgery, Louisiana State University Medical Center, Shreveport, Louisiana
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

Object. The possible role of the polyamine interconversion pathway on edema formation, traumatic injury volume, and tissue polyamine levels after traumatic brain injury (TBI) was studied using an inhibitor of the interconversion pathway enzyme, polyamine oxidase.

Methods. Experimental TBI was induced in Sprague—Dawley rats by using a controlled cortical impact device at a velocity of 3 m/second, resulting in a 2-mm deformation. Immediately after TBI was induced, 100 mg/kg of N1,N4-bis(2,3-butadienyl)-1,4-butanediamine 2HCl (MDL 72527) or saline was injected intraperitoneally. Brain water content and tissue polyamine levels were measured at 24 hours after TBI. Traumatic injury volume was evaluated using 2% cresyl violet solution 7 days after TBI occurred. The MDL 72527 treatment significantly reduced brain edema (80.4 ± 0.8% compared with 81.2 ± 1.2%, p < 0.05) and injury volume (30.1 ± 6.6 mm3 compared with 42.7 ± 13.3 mm3, p < 0.05) compared with the saline treatment. The TBI caused a significant increase in tissue putrescine levels at the traumatized site (65.5 ± 26.5 pmol/g in the cortex and 70.9 ± 22.4 pmol/g in the hippocampus) compared with the nontraumatized site (7 ± 2.4 pmol/g in the cortex and 11.4 ± 6.4 pmol/g in the hippocampus). The increase in putrescine levels in both the traumatized and nontraumatized cortex and hippocampus was reduced by a mean of 60% with MDL 72527 treatment.

Conclusions. These results demonstrate, for the first time, that the polyamine interconversion pathway has an important role in the increase of putrescine levels after TBI and that the polyamine oxidase inhibitors, blockers of the interconversion pathway, can be neuroprotective against edema formation and necrotic cavitation after TBI.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address reprint requests to: Robert J. Dempsey, M.D., Department of Neurological Surgery, University of Wisconsin, H4/338 Clinical Science Center, 600 Highland Avenue, Madison, Wisconsin 53792.
  • 1.

    Başkaya MK, , Rao AM, & Doğan A, et al: The biphasic opening of the blood-brain barrier breakdown in the cortex and hippocampus after traumatic brain injury in rats. Neurosci Lett 226:3336, 1997 Başkaya MK, Rao AM, Doğan A, et al: The biphasic opening of the blood-brain barrier breakdown in the cortex and hippocampus after traumatic brain injury in rats. Neurosci Lett 226:33–36, 1997

    • Search Google Scholar
    • Export Citation
  • 2.

    Başkaya MK, , Rao AM, & Prasad MR, et al: Regional activity of ornithine decarboxylase and edema formation after traumatic brain injury. Neurosurgery 38:140145, 1996 Başkaya MK, Rao AM, Prasad MR, et al: Regional activity of ornithine decarboxylase and edema formation after traumatic brain injury. Neurosurgery 38:140–145, 1996

    • Search Google Scholar
    • Export Citation
  • 3.

    Başkaya MK, , Rao AM, & Puckett L, et al: Effect of difluoromethylornithine treatment on regional ornithine decarboxylase activity and edema formation after experimental brain injury. J Neurotrauma 13:8592, 1996 Başkaya MK, Rao AM, Puckett L, et al: Effect of difluoromethylornithine treatment on regional ornithine decarboxylase activity and edema formation after experimental brain injury. J Neurotrauma 13:85–92, 1996

    • Search Google Scholar
    • Export Citation
  • 4.

    Bolkenius FN, , Bey P, & Seiler N: Specific inhibition of polyamine oxidase in vivo is a method for the elucidation of its physiological role. Biochim Biophys Acta 838:6976, 1985 Bolkenius FN, Bey P, Seiler N: Specific inhibition of polyamine oxidase in vivo is a method for the elucidation of its physiological role. Biochim Biophys Acta 838:69–76, 1985

    • Search Google Scholar
    • Export Citation
  • 5.

    Cockroft KM, , Meistrell M III, & Cerami A, et al: Neurotoxicity of polyamines and neuroprotective effects of aminoguanidine. Surg Forum 46:578580, 1995 Cockroft KM, Meistrell M III, Cerami A, et al: Neurotoxicity of polyamines and neuroprotective effects of aminoguanidine. Surg Forum 46:578–580, 1995

    • Search Google Scholar
    • Export Citation
  • 6.

    Cortez SC, , McIntosh TK, & Noble LJ: Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res 482:271282, 1989 Cortez SC, McIntosh TK, Noble LJ: Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res 482:271–282, 1989

    • Search Google Scholar
    • Export Citation
  • 7.

    Dienel GA, , Cruz NF, & Rosenfeld SJ: Temporal profiles of proteins responsive to transient ischemia. J Neurochem 44:600610, 1985 Dienel GA, Cruz NF, Rosenfeld SJ: Temporal profiles of proteins responsive to transient ischemia. J Neurochem 44:600–610, 1985

    • Search Google Scholar
    • Export Citation
  • 8.

    Dixon CE, , Clifton GL, & Lighthall JW, et al: A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Meth 39:253262, 1991 Dixon CE, Clifton GL, Lighthall JW, et al: A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Meth 39:253–262, 1991

    • Search Google Scholar
    • Export Citation
  • 9.

    Gilad GM, , Gilad VH, & Wyatt RJ, et al: Chronic lithium treatment prevents the dexamethasone-induced increase of brain polyamine metabolizing enzymes. Life Sci 50:PL149PL154, 1992 Gilad GM, Gilad VH, Wyatt RJ, et al: Chronic lithium treatment prevents the dexamethasone-induced increase of brain polyamine metabolizing enzymes. Life Sci 50:PL149–PL154, 1992

    • Search Google Scholar
    • Export Citation
  • 10.

    Ha HC, , Woster PM, & Yager JD, et al: The role of polyamine catabolism in polyamine analogue-induced programmed cell death. Proc Natl Acad Sci USA 94:1155711562, 1997 Ha HC, Woster PM, Yager JD, et al: The role of polyamine catabolism in polyamine analogue-induced programmed cell death. Proc Natl Acad Sci USA 94:11557–11562, 1997

    • Search Google Scholar
    • Export Citation
  • 11.

    Henley CM, , Muszynski C, & Cherian L, et al: Activation of ornithine decarboxylase and accumulation of putrescine after traumatic brain injury. J Neurotrauma 13:487496, 1996 Henley CM, Muszynski C, Cherian L, et al: Activation of ornithine decarboxylase and accumulation of putrescine after traumatic brain injury. J Neurotrauma 13:487–496, 1996

    • Search Google Scholar
    • Export Citation
  • 12.

    Ientile R, , De Luca G, & Di Giorgio RM, et al: Glucocorticoid regulation of spermidine acetylation in the rat brain. J Neurochem 51:677682, 1988 Ientile R, De Luca G, Di Giorgio RM, et al: Glucocorticoid regulation of spermidine acetylation in the rat brain. J Neurochem 51:677–682, 1988

    • Search Google Scholar
    • Export Citation
  • 13.

    Ivanova S, , Botchkina GI, & Al-Abed Y, et al: Cerebral ischemia enhances polyamine oxidation: identification of enzymatically formed 3-aminopropanal as an endogenous mediator of neuronal and glial cell death. J Exp Med 188:327340, 1998 Ivanova S, Botchkina GI, Al-Abed Y, et al: Cerebral ischemia enhances polyamine oxidation: identification of enzymatically formed 3-aminopropanal as an endogenous mediator of neuronal and glial cell death. J Exp Med 188:327–340, 1998

    • Search Google Scholar
    • Export Citation
  • 14.

    Kabra PM, , Lee HK, & Lubich WP, et al: Solid-phase extraction and determination of dansyl derivatives of unconjugated and acetylated polyamines by reversed-phase liquid chromatography: improved separation systems for polyamines in cerebrospinal fluid, urine and tissue. J Chromatogr 380:1932, 1986 Kabra PM, Lee HK, Lubich WP, et al: Solid-phase extraction and determination of dansyl derivatives of unconjugated and acetylated polyamines by reversed-phase liquid chromatography: improved separation systems for polyamines in cerebrospinal fluid, urine and tissue. J Chromatogr 380:19–32, 1986

    • Search Google Scholar
    • Export Citation
  • 15.

    Kimelberg HK: Current concepts of brain edema. Review of laboratory investigations. J Neurosurg 83:10511059, 1995 Kimelberg HK: Current concepts of brain edema. Review of laboratory investigations. J Neurosurg 83:1051–1059, 1995

    • Search Google Scholar
    • Export Citation
  • 16.

    Kleihues P, , Hossmann KA, & Pegg AE, et al: Resuscitation of the monkey brain after one hour complete ischemia. III. Indications of metabolic recovery. Brain Res 95:6173, 1975 Kleihues P, Hossmann KA, Pegg AE, et al: Resuscitation of the monkey brain after one hour complete ischemia. III. Indications of metabolic recovery. Brain Res 95:61–73, 1975

    • Search Google Scholar
    • Export Citation
  • 17.

    Koenig H, , Goldstone AD, & Lu CY: Blood brain barrier breakdown in brain edema following cold injury is mediated by microvascular polyamines. Biochem Biophys Res Commun 116:10391048, 1983 Koenig H, Goldstone AD, Lu CY: Blood brain barrier breakdown in brain edema following cold injury is mediated by microvascular polyamines. Biochem Biophys Res Commun 116:1039–1048, 1983

    • Search Google Scholar
    • Export Citation
  • 18.

    Li Y, , Chopp M, & Jiang N, et al: Temporal profile of in situ DNA fragmentation after transient middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 15:389397, 1995 Li Y, Chopp M, Jiang N, et al: Temporal profile of in situ DNA fragmentation after transient middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 15:389–397, 1995

    • Search Google Scholar
    • Export Citation
  • 19.

    Rink A, , Fung KM, & Trojanowski JQ, et al: Evidence of apoptotic cell death after experimental traumatic brain injury in the rat. Am J Pathol 147:15751583, 1995 Rink A, Fung KM, Trojanowski JQ, et al: Evidence of apoptotic cell death after experimental traumatic brain injury in the rat. Am J Pathol 147:1575–1583, 1995

    • Search Google Scholar
    • Export Citation
  • 20.

    Seiler N: Polyamine oxidase, properties and functions. Prog Brain Res 106:333344, 1995 Seiler N: Polyamine oxidase, properties and functions. Prog Brain Res 106:333–344, 1995

    • Search Google Scholar
    • Export Citation
  • 21.

    Seiler N, & Bolkenius FN: Polyamine reutilization and turnover in brain. Neurochem Res 10:529544, 1985 Seiler N, Bolkenius FN: Polyamine reutilization and turnover in brain. Neurochem Res 10:529–544, 1985

    • Search Google Scholar
    • Export Citation
  • 22.

    Shohami E, , Nates JL, & Glantz L, et al: Changes in brain polyamine levels following head injury. Exp Neurol 117:189195, 1992 Shohami E, Nates JL, Glantz L, et al: Changes in brain polyamine levels following head injury. Exp Neurol 117:189–195, 1992

    • Search Google Scholar
    • Export Citation
  • 23.

    Tasdemiroglu E, , Christenberry PD, & Ardell JL, et al: Effects of antioxidants on the blood-brain barrier and postischemic hyperemia. Acta Neurochir 131:302309, 1994 Tasdemiroglu E, Christenberry PD, Ardell JL, et al: Effects of antioxidants on the blood-brain barrier and postischemic hyperemia. Acta Neurochir 131:302–309, 1994

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 197 128 3
Full Text Views 197 15 1
PDF Downloads 103 8 1
EPUB Downloads 0 0 0