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 language | English |
|---|---|
| Pages (from-to) | 1427-1436 |
| Number of pages | 10 |
| Journal | Neurosurgery |
| Volume | 43 |
| Issue number | 6 |
| State | Published - Dec 1 1998 |
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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 journal › Article
}
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 -