Inducible nitric oxide synthase expression after traumatic brain injury and neuroprotection with aminoguanidine treatment in rats

Kojiro Wada, Katina Chatzipanteli, Susan Kraydieh, Raul Busto, W. Dalton Dietrich

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

OBJECTIVE: We investigated the time course of inducible nitric oxide synthase (iNOS) enzymatic activity and immunocytochemical localization of iNOS expression after traumatic brain injury (TBI), as well as the possible role of iNOS in the pathogenesis of TBI. METHODS: Male Sprague-Dawley rats were anesthetized and underwent moderate parasagittal fluid-percussion brain injury. Rats were decapitated 5 minutes, 6 hours, 1 day, 3 days, 7 days, or 14 days later, and iNOS enzymatic activities were measured (n = 6-8). To determine whether nitric oxide produced by iNOS contributed to the histopathological consequences of TBI, inhibition of iNOS activity using aminoguanidine (intraperitoneal injections of 100 mg/kg aminoguanidine [n = 9] or vehicle [n = 8], twice each day) was conducted for 3 days. RESULTS: Significantly elevated iNOS activity was detected at 3 days (276.8 ± 72.3% of contralateral value, means ± standard errors; P < 0.05), and the most robust increase occurred 7 days after TBI (608.0 ± 127.0%, P < 0.01) in the injured parietal cerebral cortex. Immunostaining for iNOS and glial fibrillary acidic protein, at 3 and 7 days after TBI, revealed that the major cellular sources of iNOS expression were cortical Layer 1 astrocytes and macrophages within the subarachnoid space. Administration of aminoguanidine did not reduce contusion volume significantly; however, treatment reduced total cortical necrotic neuron counts (1367.6 ± 210.3; P < 0.01, compared with vehicle, 2808.5 ± 325.1). CONCLUSION: These data indicate that iNOS is expressed after moderate parasagittal fluid-percussion brain injury, in a time-dependent manner, and that inhibition of iNOS synthesis improves histopathological outcomes. Thus, inhibition of iNOS activation may represent a potential therapeutic strategy for the treatment of TBI.

Original languageEnglish
Pages (from-to)1427-1436
Number of pages10
JournalNeurosurgery
Volume43
Issue number6
StatePublished - Dec 1 1998

Fingerprint

Nitric Oxide Synthase Type II
Therapeutics
Percussion
Brain Injuries
pimagedine
Traumatic Brain Injury
Neuroprotection
Parietal Lobe
Subarachnoid Space
Contusions
Glial Fibrillary Acidic Protein
Intraperitoneal Injections
Astrocytes
Cerebral Cortex
Sprague Dawley Rats
Nitric Oxide
Macrophages
Neurons

Keywords

  • Aminoguanidine
  • Fluid-percussion brain injury
  • Inducible nitric oxide synthase
  • Nitric oxide
  • Nitric oxide inhibitor
  • Rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Inducible nitric oxide synthase expression after traumatic brain injury and neuroprotection with aminoguanidine treatment in rats. / Wada, Kojiro; Chatzipanteli, Katina; Kraydieh, Susan; Busto, Raul; Dalton Dietrich, W.

In: Neurosurgery, Vol. 43, No. 6, 01.12.1998, p. 1427-1436.

Research output: Contribution to journalArticle

Wada, Kojiro ; Chatzipanteli, Katina ; Kraydieh, Susan ; Busto, Raul ; Dalton Dietrich, W. / Inducible nitric oxide synthase expression after traumatic brain injury and neuroprotection with aminoguanidine treatment in rats. In: Neurosurgery. 1998 ; Vol. 43, No. 6. pp. 1427-1436.
@article{71d659578688475e9fed9e8e65b7a397,
title = "Inducible nitric oxide synthase expression after traumatic brain injury and neuroprotection with aminoguanidine treatment in rats",
abstract = "OBJECTIVE: We investigated the time course of inducible nitric oxide synthase (iNOS) enzymatic activity and immunocytochemical localization of iNOS expression after traumatic brain injury (TBI), as well as the possible role of iNOS in the pathogenesis of TBI. METHODS: Male Sprague-Dawley rats were anesthetized and underwent moderate parasagittal fluid-percussion brain injury. Rats were decapitated 5 minutes, 6 hours, 1 day, 3 days, 7 days, or 14 days later, and iNOS enzymatic activities were measured (n = 6-8). To determine whether nitric oxide produced by iNOS contributed to the histopathological consequences of TBI, inhibition of iNOS activity using aminoguanidine (intraperitoneal injections of 100 mg/kg aminoguanidine [n = 9] or vehicle [n = 8], twice each day) was conducted for 3 days. RESULTS: Significantly elevated iNOS activity was detected at 3 days (276.8 ± 72.3{\%} of contralateral value, means ± standard errors; P < 0.05), and the most robust increase occurred 7 days after TBI (608.0 ± 127.0{\%}, P < 0.01) in the injured parietal cerebral cortex. Immunostaining for iNOS and glial fibrillary acidic protein, at 3 and 7 days after TBI, revealed that the major cellular sources of iNOS expression were cortical Layer 1 astrocytes and macrophages within the subarachnoid space. Administration of aminoguanidine did not reduce contusion volume significantly; however, treatment reduced total cortical necrotic neuron counts (1367.6 ± 210.3; P < 0.01, compared with vehicle, 2808.5 ± 325.1). CONCLUSION: These data indicate that iNOS is expressed after moderate parasagittal fluid-percussion brain injury, in a time-dependent manner, and that inhibition of iNOS synthesis improves histopathological outcomes. Thus, inhibition of iNOS activation may represent a potential therapeutic strategy for the treatment of TBI.",
keywords = "Aminoguanidine, Fluid-percussion brain injury, Inducible nitric oxide synthase, Nitric oxide, Nitric oxide inhibitor, Rat",
author = "Kojiro Wada and Katina Chatzipanteli and Susan Kraydieh and Raul Busto and {Dalton Dietrich}, W.",
year = "1998",
month = "12",
day = "1",
language = "English",
volume = "43",
pages = "1427--1436",
journal = "Neurosurgery",
issn = "0148-396X",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Inducible nitric oxide synthase expression after traumatic brain injury and neuroprotection with aminoguanidine treatment in rats

AU - Wada, Kojiro

AU - Chatzipanteli, Katina

AU - Kraydieh, Susan

AU - Busto, Raul

AU - Dalton Dietrich, W.

PY - 1998/12/1

Y1 - 1998/12/1

N2 - OBJECTIVE: We investigated the time course of inducible nitric oxide synthase (iNOS) enzymatic activity and immunocytochemical localization of iNOS expression after traumatic brain injury (TBI), as well as the possible role of iNOS in the pathogenesis of TBI. METHODS: Male Sprague-Dawley rats were anesthetized and underwent moderate parasagittal fluid-percussion brain injury. Rats were decapitated 5 minutes, 6 hours, 1 day, 3 days, 7 days, or 14 days later, and iNOS enzymatic activities were measured (n = 6-8). To determine whether nitric oxide produced by iNOS contributed to the histopathological consequences of TBI, inhibition of iNOS activity using aminoguanidine (intraperitoneal injections of 100 mg/kg aminoguanidine [n = 9] or vehicle [n = 8], twice each day) was conducted for 3 days. RESULTS: Significantly elevated iNOS activity was detected at 3 days (276.8 ± 72.3% of contralateral value, means ± standard errors; P < 0.05), and the most robust increase occurred 7 days after TBI (608.0 ± 127.0%, P < 0.01) in the injured parietal cerebral cortex. Immunostaining for iNOS and glial fibrillary acidic protein, at 3 and 7 days after TBI, revealed that the major cellular sources of iNOS expression were cortical Layer 1 astrocytes and macrophages within the subarachnoid space. Administration of aminoguanidine did not reduce contusion volume significantly; however, treatment reduced total cortical necrotic neuron counts (1367.6 ± 210.3; P < 0.01, compared with vehicle, 2808.5 ± 325.1). CONCLUSION: These data indicate that iNOS is expressed after moderate parasagittal fluid-percussion brain injury, in a time-dependent manner, and that inhibition of iNOS synthesis improves histopathological outcomes. Thus, inhibition of iNOS activation may represent a potential therapeutic strategy for the treatment of TBI.

AB - OBJECTIVE: We investigated the time course of inducible nitric oxide synthase (iNOS) enzymatic activity and immunocytochemical localization of iNOS expression after traumatic brain injury (TBI), as well as the possible role of iNOS in the pathogenesis of TBI. METHODS: Male Sprague-Dawley rats were anesthetized and underwent moderate parasagittal fluid-percussion brain injury. Rats were decapitated 5 minutes, 6 hours, 1 day, 3 days, 7 days, or 14 days later, and iNOS enzymatic activities were measured (n = 6-8). To determine whether nitric oxide produced by iNOS contributed to the histopathological consequences of TBI, inhibition of iNOS activity using aminoguanidine (intraperitoneal injections of 100 mg/kg aminoguanidine [n = 9] or vehicle [n = 8], twice each day) was conducted for 3 days. RESULTS: Significantly elevated iNOS activity was detected at 3 days (276.8 ± 72.3% of contralateral value, means ± standard errors; P < 0.05), and the most robust increase occurred 7 days after TBI (608.0 ± 127.0%, P < 0.01) in the injured parietal cerebral cortex. Immunostaining for iNOS and glial fibrillary acidic protein, at 3 and 7 days after TBI, revealed that the major cellular sources of iNOS expression were cortical Layer 1 astrocytes and macrophages within the subarachnoid space. Administration of aminoguanidine did not reduce contusion volume significantly; however, treatment reduced total cortical necrotic neuron counts (1367.6 ± 210.3; P < 0.01, compared with vehicle, 2808.5 ± 325.1). CONCLUSION: These data indicate that iNOS is expressed after moderate parasagittal fluid-percussion brain injury, in a time-dependent manner, and that inhibition of iNOS synthesis improves histopathological outcomes. Thus, inhibition of iNOS activation may represent a potential therapeutic strategy for the treatment of TBI.

KW - Aminoguanidine

KW - Fluid-percussion brain injury

KW - Inducible nitric oxide synthase

KW - Nitric oxide

KW - Nitric oxide inhibitor

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=0031761348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031761348&partnerID=8YFLogxK

M3 - Article

VL - 43

SP - 1427

EP - 1436

JO - Neurosurgery

JF - Neurosurgery

SN - 0148-396X

IS - 6

ER -