Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with... AbstractOBJECTIVEWe investigated the time course of inducible nitric oxide synthase (iNOS) enzymatic activity and immunocy to chemical localization of iNOS expression after traumatic brain injury (TBI), as well as the possible role of iNOS in the pathogenesis of TBI.METHODSMale 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 100mg/kg aminoguanidine [n=9] or vehicle [n=8], twice each day) was conducted for 3 days.RESULTSSignificantly 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 macro phages 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).CONCLUSIONThese 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Inducible N itric O xide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats Kojiro Wada, M.D., Katina Chatzipanteli, Ph.D., Susan Kraydieh, B.S., Raul Busto, B.S., W. Dalton Dietrich, Ph.D. Departments of Neurology (KW, KC, RB, W D D ) and Neurological Surgery (WDD), Neurotrauma Research Center (KW, KC, RB, W D D ), and The Miami Project to Cure Paralysis (SK, W D D ), University of Miami School of Medicine, Miami, Florida, and Department of Neurosurgery (KW), National Defense Medical College, Tokorozawa, Japan O B JE C T IV E : W e i n v e s t i g a t e d t h e t i m e c o u r s e o f i n d u c i b l e n i t r i c o x i d e s y n t h a s e ( i N O S ) e n z y m a t i c a c t i v i t y a n d i m m u n o c y t o c h e m i c a l l o c a l i z a t i o n o f i N O S e x p r e s s i o n a f t e r t r a u m a t i c b r a i n i n j u r y ( T B I ) , a s w e l l a s t h e p o s s i b l e role o f i N O S i n t h e p a t h o g e n e s i s o f T B I . M E T H O D S : M a l e S p r a g u e - D a w l e y r a t s w e r e a n e s t h e t i z e d a n d u n d e r w e n t m o d e r a t e p a r a s a g i t t a l f l u i d - p e r c u s s i o n b rain i n j u r y . R a t s w e r e d e c a p i t a t e d 5 m i n u t e s , 6 h o u r s , 1 d a y , 3 d a y s , 7 d a y s , o r 1 4 d a y s l a t e r , a n d i N O S e n z y m a t i c a c t i v i t i e s w e r e m e a s u r e d ( n = 6 - 8 ) . T o d e t e r m i n e w h e t h e r n i t r i c o x i d e p r o d u c e d b y i N O S c o n t r i b u t e d to t h e h i s t o p a t h o l o g i c a l c o n s e q u e n c e s o f T B I , i n h i b i t i o n o f i N O S a c t i v i t y u s i n g a m i n o g u a n i d i n e ( i n t r a p e r i t o n e a l i n j e c t i o n s o f 1 0 0 m g / k g a m i n o g u a n i d i n e [ n = 9 ] o r v e h i c l e [ n = 8 ] , t w i c e e a c h d a y ) w a s c o n d u c t e d f o r 3 d a y s . RESULTS: S i g n i f i c a n t l y e l e v a t e d i N O S a c t i v i...
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Publisher
Oxford University Press
Copyright
© Published by Oxford University Press.
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1097/00006123-199812000-00096
Publisher site
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Abstract

AbstractOBJECTIVEWe investigated the time course of inducible nitric oxide synthase (iNOS) enzymatic activity and immunocy to chemical localization of iNOS expression after traumatic brain injury (TBI), as well as the possible role of iNOS in the pathogenesis of TBI.METHODSMale 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 100mg/kg aminoguanidine [n=9] or vehicle [n=8], twice each day) was conducted for 3 days.RESULTSSignificantly 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 macro phages 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).CONCLUSIONThese 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.

Journal

NeurosurgeryOxford University Press

Published: Dec 1, 1998

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