The Effect of Pentoxifylline on IL-1beta and TNF-alpha mRNA Gene Expression in Hypoxic-Ischemic Brain Injury of Immature Rat.
- Author:
Kyoung Burm KIM
1
;
Gi Hyun JEON
;
Young Rae KIM
;
Jung Hwa LEE
;
Kee Hyoung LEE
;
Baik Lin EUN
;
Soon Kyum KIM
Author Information
1. Department of Pediatrics, College of Medicine and School of Medicine, Korea University, Korea.
- Publication Type:Original Article
- Keywords:
IL-1beta;
TNF-alpha;
Pentoxifylline;
Hypoxia-ischemia;
Immature brain
- MeSH:
3',5'-Cyclic-AMP Phosphodiesterases;
Animals;
Anoxia;
Brain Injuries*;
Brain*;
Carotid Arteries;
Central Nervous System;
Cytokines;
DNA, Complementary;
Gene Expression*;
Hypoxia-Ischemia, Brain;
Incidence;
Ischemia;
Ligation;
Necrosis;
Pentoxifylline*;
Polymerase Chain Reaction;
Rats*;
Reverse Transcription;
RNA, Messenger*;
Tumor Necrosis Factor-alpha*
- From:
Journal of the Korean Child Neurology Society
1999;7(2):181-187
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Interleukin-1beta(IL-1beta) and Tumor necrosis factor-alpha(TNF-alpha) are multifunctional cytokines that may play important roles both in the normal development of central nervous system and in the response of brain to diverse forms of injury. IL-1beta and TNF-alpha have potent proinflammatory action and the potential to modulate cell growth. Cerebral hypoxia-ischemia selectively stimulates IL-1beta and TNF-alpha gene expression in brain regions susceptible to irreversible injury in perinatal rats. Pentoxifylline, a cAMP phosphodiesterase inhibitor, attenuates hypoxic-ischemic brain injury in immature rats and inhibits TNF-alpha expression at the transcription level. We hypothesize that pentoxifylline would attenuate the expression of IL-1beta and TNF-alpha mRNA gene expression on hypoxic-ischemic brain injury in immature rats. METHODS: To elicit focal hypoxic-ischemic brain injury, 7-d-old(P7) rats underwent right carotid artery ligation, followed by 3 hr of hypoxia(fractional concentration of inspired O2=0.08). In 3 rats, pentoxifylline(40mg/kg) was injected into the intraperitoneal cavity immediately before and after hypoxia. The other 4 rats were given PBS solutions. IL-1beta and TNF-alpha mRNA content were measured by reverse transcription followed by polymerase chain reaction amplification(RT-PCR) in the samples prepared from the lesioned and contralateral hemispheres killed 4 hr post-hypoxia. cDNA were amplified with primers specific for IL-1beta and TNF-alpha. and also amplified with GAPDH primers which served as an internal control. RESULTS: In control group, hypoxia-ischemia induced IL-1beta and TNF-alpha mRNA expression from the lesioned hemisphere in immature rat brain. In pentoxifylline treated group, IL-1beta and TNF-alpha mRNA expression were attenuated at 4 hr post hypoxia- ischemia. CONCLUSION: Preteatment with pentoxifylline decreased incidence and severity of hypoxic-ischemic injury in immature rat brain. Pentoxifylline attenuated the expression of IL-1beta and TNF-alpha gene on hypoxic-ischemic injury in immature rat brain. IL-1beta and TNF-alpha may play important roles in the response of the developing brain to acute hypoxic-ischemic injury.
