Contribution of polyamine oxidase to brain injury after trauma

Aclan Dogan, A. Muralikrishna Rao, Muştafa K. Baskaya, James Hatcher, Cuneyt Temiz, V. L Raghavendra Rao, Robert J. Dempsey

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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 N',N'-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.

Original languageEnglish (US)
Pages (from-to)1078-1082
Number of pages5
JournalJournal of Neurosurgery
Volume90
Issue number6
StatePublished - Jun 1999
Externally publishedYes

Fingerprint

Brain Injuries
Wounds and Injuries
Polyamines
Putrescine
Hippocampus
Edema
polyamine oxidase
Traumatic Brain Injury
Brain Edema
Sprague Dawley Rats
Equipment and Supplies
MDL 72527
Water
Brain
Enzymes

Keywords

  • Cerebral edema
  • Cerebral ischemia
  • Interconversion pathway
  • N,N- bis(2,3-butadienyl)-1,4-butanediamine 2HCl
  • Polyamine oxidase
  • Rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Dogan, A., Rao, A. M., Baskaya, M. K., Hatcher, J., Temiz, C., Rao, V. L. R., & Dempsey, R. J. (1999). Contribution of polyamine oxidase to brain injury after trauma. Journal of Neurosurgery, 90(6), 1078-1082.

Contribution of polyamine oxidase to brain injury after trauma. / Dogan, Aclan; Rao, A. Muralikrishna; Baskaya, Muştafa K.; Hatcher, James; Temiz, Cuneyt; Rao, V. L Raghavendra; Dempsey, Robert J.

In: Journal of Neurosurgery, Vol. 90, No. 6, 06.1999, p. 1078-1082.

Research output: Contribution to journalArticle

Dogan, A, Rao, AM, Baskaya, MK, Hatcher, J, Temiz, C, Rao, VLR & Dempsey, RJ 1999, 'Contribution of polyamine oxidase to brain injury after trauma', Journal of Neurosurgery, vol. 90, no. 6, pp. 1078-1082.
Dogan A, Rao AM, Baskaya MK, Hatcher J, Temiz C, Rao VLR et al. Contribution of polyamine oxidase to brain injury after trauma. Journal of Neurosurgery. 1999 Jun;90(6):1078-1082.
Dogan, Aclan ; Rao, A. Muralikrishna ; Baskaya, Muştafa K. ; Hatcher, James ; Temiz, Cuneyt ; Rao, V. L Raghavendra ; Dempsey, Robert J. / Contribution of polyamine oxidase to brain injury after trauma. In: Journal of Neurosurgery. 1999 ; Vol. 90, No. 6. pp. 1078-1082.
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abstract = "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 N',N'-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.",
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AU - Rao, A. Muralikrishna

AU - Baskaya, Muştafa K.

AU - Hatcher, James

AU - Temiz, Cuneyt

AU - Rao, V. L Raghavendra

AU - Dempsey, Robert J.

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N2 - 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 N',N'-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.

AB - 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 N',N'-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.

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