Temporal and segmental distribution of constitutive and inducible nitric oxide synthases after traumatic spinal cord injury

Effect of aminoguanidine treatment

Katina Chatzipanteli, Ronaldo Garcia, Alexander Marcillo, Kim E. Loor, Susan Kraydieh, W. Dalton Dietrich

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Nitric oxide (NO) has been shown to play an important role in the pathophysiology of traumatic brain injury (TBI) and cerebral ischemia. However, its contribution to the pathogenesis of traumatic spinal cord injury (SCI) remains to be clarified. This study determined the time course of constitutive and inducible nitric oxide synthases (cNOS and iNOS, respectively) after SCI. Rats underwent moderate SCI at T10 using the NYU impactor device and were allowed to survive for 3, 6, or 24 h and 3 days after SCI (n = 5 in each group). For the determination of enzymatic activities, spinal cords were dissected into five segments, including levels rostral and caudal (remote) to the injury site. Other rats were perfusion fixed for the immunohistochemical localization of iNOS protein levels. cNOS activity was significantly decreased at 3 and 6 h within the traumatized T10 segment and at 3, 6, and 24 h at the rostral (T9) level (p < 0.05). Rostral (T8) and caudal (T11, T12) to the injury site cNOS activity was also decreased at 3 h after injury (p < 0.05). However, cNOS activity returned to control levels within 6 h at T8, T11 and T12 and at one day at T10 and T9 segments. iNOS enzymatic activity was elevated at all time points tested (p < 0.05), with the most robust increase observed at 24 h. Immunostaining for iNOS at 24 h revealed that a significant cellular source of iNOS protein appeared to be invading polymorphonuclear leukocytes (PMNLs). To assess the functional consequences of iNOS inhibition, aminoguanidine treatment was initiated 5 min after SCI and rats tested using the BBB open field locomotor score. Treated rats demonstrated significantly improved hindlimb function up to 7 weeks after SCI. Histopathological analysis of contusion volume showed that aminoguanidine treatment decreased lesion volume by 37% (p < 0.05). In conclusion, these results indicate that (1) cNOS and iNOS activities are regionally and temporally affected after moderate SCI, (2) the early accumulation of PMNLs are a potentially significant source of NO-induced cytotoxic products, and (3) acute aminoguanidine treatment significantly improves functional and histopathological outcome after SCI.

Original languageEnglish
Pages (from-to)639-651
Number of pages13
JournalJournal of Neurotrauma
Volume19
Issue number5
StatePublished - Jun 13 2002

Fingerprint

Nitric Oxide Synthase Type II
Spinal Cord Injuries
Brain Ischemia
Wounds and Injuries
Nitric Oxide
Neutrophils
pimagedine
Contusions
Hindlimb
Spinal Cord
Proteins
Perfusion
Equipment and Supplies

Keywords

  • 3-nitrotyrosine
  • Immunohistochemistry
  • Nitric oxide
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Temporal and segmental distribution of constitutive and inducible nitric oxide synthases after traumatic spinal cord injury : Effect of aminoguanidine treatment. / Chatzipanteli, Katina; Garcia, Ronaldo; Marcillo, Alexander; Loor, Kim E.; Kraydieh, Susan; Dalton Dietrich, W.

In: Journal of Neurotrauma, Vol. 19, No. 5, 13.06.2002, p. 639-651.

Research output: Contribution to journalArticle

Chatzipanteli, Katina ; Garcia, Ronaldo ; Marcillo, Alexander ; Loor, Kim E. ; Kraydieh, Susan ; Dalton Dietrich, W. / Temporal and segmental distribution of constitutive and inducible nitric oxide synthases after traumatic spinal cord injury : Effect of aminoguanidine treatment. In: Journal of Neurotrauma. 2002 ; Vol. 19, No. 5. pp. 639-651.
@article{593203b2bb6149ddb43950420c4fb618,
title = "Temporal and segmental distribution of constitutive and inducible nitric oxide synthases after traumatic spinal cord injury: Effect of aminoguanidine treatment",
abstract = "Nitric oxide (NO) has been shown to play an important role in the pathophysiology of traumatic brain injury (TBI) and cerebral ischemia. However, its contribution to the pathogenesis of traumatic spinal cord injury (SCI) remains to be clarified. This study determined the time course of constitutive and inducible nitric oxide synthases (cNOS and iNOS, respectively) after SCI. Rats underwent moderate SCI at T10 using the NYU impactor device and were allowed to survive for 3, 6, or 24 h and 3 days after SCI (n = 5 in each group). For the determination of enzymatic activities, spinal cords were dissected into five segments, including levels rostral and caudal (remote) to the injury site. Other rats were perfusion fixed for the immunohistochemical localization of iNOS protein levels. cNOS activity was significantly decreased at 3 and 6 h within the traumatized T10 segment and at 3, 6, and 24 h at the rostral (T9) level (p < 0.05). Rostral (T8) and caudal (T11, T12) to the injury site cNOS activity was also decreased at 3 h after injury (p < 0.05). However, cNOS activity returned to control levels within 6 h at T8, T11 and T12 and at one day at T10 and T9 segments. iNOS enzymatic activity was elevated at all time points tested (p < 0.05), with the most robust increase observed at 24 h. Immunostaining for iNOS at 24 h revealed that a significant cellular source of iNOS protein appeared to be invading polymorphonuclear leukocytes (PMNLs). To assess the functional consequences of iNOS inhibition, aminoguanidine treatment was initiated 5 min after SCI and rats tested using the BBB open field locomotor score. Treated rats demonstrated significantly improved hindlimb function up to 7 weeks after SCI. Histopathological analysis of contusion volume showed that aminoguanidine treatment decreased lesion volume by 37{\%} (p < 0.05). In conclusion, these results indicate that (1) cNOS and iNOS activities are regionally and temporally affected after moderate SCI, (2) the early accumulation of PMNLs are a potentially significant source of NO-induced cytotoxic products, and (3) acute aminoguanidine treatment significantly improves functional and histopathological outcome after SCI.",
keywords = "3-nitrotyrosine, Immunohistochemistry, Nitric oxide, Nitric oxide synthase",
author = "Katina Chatzipanteli and Ronaldo Garcia and Alexander Marcillo and Loor, {Kim E.} and Susan Kraydieh and {Dalton Dietrich}, W.",
year = "2002",
month = "6",
day = "13",
language = "English",
volume = "19",
pages = "639--651",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "5",

}

TY - JOUR

T1 - Temporal and segmental distribution of constitutive and inducible nitric oxide synthases after traumatic spinal cord injury

T2 - Effect of aminoguanidine treatment

AU - Chatzipanteli, Katina

AU - Garcia, Ronaldo

AU - Marcillo, Alexander

AU - Loor, Kim E.

AU - Kraydieh, Susan

AU - Dalton Dietrich, W.

PY - 2002/6/13

Y1 - 2002/6/13

N2 - Nitric oxide (NO) has been shown to play an important role in the pathophysiology of traumatic brain injury (TBI) and cerebral ischemia. However, its contribution to the pathogenesis of traumatic spinal cord injury (SCI) remains to be clarified. This study determined the time course of constitutive and inducible nitric oxide synthases (cNOS and iNOS, respectively) after SCI. Rats underwent moderate SCI at T10 using the NYU impactor device and were allowed to survive for 3, 6, or 24 h and 3 days after SCI (n = 5 in each group). For the determination of enzymatic activities, spinal cords were dissected into five segments, including levels rostral and caudal (remote) to the injury site. Other rats were perfusion fixed for the immunohistochemical localization of iNOS protein levels. cNOS activity was significantly decreased at 3 and 6 h within the traumatized T10 segment and at 3, 6, and 24 h at the rostral (T9) level (p < 0.05). Rostral (T8) and caudal (T11, T12) to the injury site cNOS activity was also decreased at 3 h after injury (p < 0.05). However, cNOS activity returned to control levels within 6 h at T8, T11 and T12 and at one day at T10 and T9 segments. iNOS enzymatic activity was elevated at all time points tested (p < 0.05), with the most robust increase observed at 24 h. Immunostaining for iNOS at 24 h revealed that a significant cellular source of iNOS protein appeared to be invading polymorphonuclear leukocytes (PMNLs). To assess the functional consequences of iNOS inhibition, aminoguanidine treatment was initiated 5 min after SCI and rats tested using the BBB open field locomotor score. Treated rats demonstrated significantly improved hindlimb function up to 7 weeks after SCI. Histopathological analysis of contusion volume showed that aminoguanidine treatment decreased lesion volume by 37% (p < 0.05). In conclusion, these results indicate that (1) cNOS and iNOS activities are regionally and temporally affected after moderate SCI, (2) the early accumulation of PMNLs are a potentially significant source of NO-induced cytotoxic products, and (3) acute aminoguanidine treatment significantly improves functional and histopathological outcome after SCI.

AB - Nitric oxide (NO) has been shown to play an important role in the pathophysiology of traumatic brain injury (TBI) and cerebral ischemia. However, its contribution to the pathogenesis of traumatic spinal cord injury (SCI) remains to be clarified. This study determined the time course of constitutive and inducible nitric oxide synthases (cNOS and iNOS, respectively) after SCI. Rats underwent moderate SCI at T10 using the NYU impactor device and were allowed to survive for 3, 6, or 24 h and 3 days after SCI (n = 5 in each group). For the determination of enzymatic activities, spinal cords were dissected into five segments, including levels rostral and caudal (remote) to the injury site. Other rats were perfusion fixed for the immunohistochemical localization of iNOS protein levels. cNOS activity was significantly decreased at 3 and 6 h within the traumatized T10 segment and at 3, 6, and 24 h at the rostral (T9) level (p < 0.05). Rostral (T8) and caudal (T11, T12) to the injury site cNOS activity was also decreased at 3 h after injury (p < 0.05). However, cNOS activity returned to control levels within 6 h at T8, T11 and T12 and at one day at T10 and T9 segments. iNOS enzymatic activity was elevated at all time points tested (p < 0.05), with the most robust increase observed at 24 h. Immunostaining for iNOS at 24 h revealed that a significant cellular source of iNOS protein appeared to be invading polymorphonuclear leukocytes (PMNLs). To assess the functional consequences of iNOS inhibition, aminoguanidine treatment was initiated 5 min after SCI and rats tested using the BBB open field locomotor score. Treated rats demonstrated significantly improved hindlimb function up to 7 weeks after SCI. Histopathological analysis of contusion volume showed that aminoguanidine treatment decreased lesion volume by 37% (p < 0.05). In conclusion, these results indicate that (1) cNOS and iNOS activities are regionally and temporally affected after moderate SCI, (2) the early accumulation of PMNLs are a potentially significant source of NO-induced cytotoxic products, and (3) acute aminoguanidine treatment significantly improves functional and histopathological outcome after SCI.

KW - 3-nitrotyrosine

KW - Immunohistochemistry

KW - Nitric oxide

KW - Nitric oxide synthase

UR - http://www.scopus.com/inward/record.url?scp=0036264281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036264281&partnerID=8YFLogxK

M3 - Article

VL - 19

SP - 639

EP - 651

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 5

ER -