Preliminary study on the effect of trauma-induced secondary cellular hypoxia in brain injury.
Secondary cerebral hypoxia has recently been shown to play an important role in the outcome of patients suffering from traumatic brain injury (TBI). However, the precise mechanisms underlying secondary cerebral hypoxia are complex and interrelated. In this study, we investigate the effect of hypoxia within a rat model of trauma-induced late cerebral cortex injury. Using the hypoxia marker pimonidazole, we verified and isolated areas of the cortex that had suffered hypoxic damage. Using subsequent reverse-transcriptase PCR analyses, we found that the expressions of both transforming growth factor beta1 (TGF-beta1) and hypoxia-inducible factor-1alpha (HIF-1alpha) increased significantly under hypoxic conditions induced by TBI compared with uninjured control animals. In addition, the maximum mRNA expression of TGF-beta1 and HIF-1alpha was found at 3 days and 12h after TBI, respectively. Our data suggest that secondary cerebral hypoxia injury involves various cytokines including TGF-beta1 and HIF-1alpha. Furthermore, upon immunohistochemical analysis, both TGF-beta1 and HIF-1alpha expression were almost localized in the same types of cells by using immunohistochemical study. These results may have important implications in the understanding of trauma-induced secondary cerebral hypoxia injury.
Huang
Ren-Qiang
RQ
Department of Neurosurgery, School of Medicine, Second Military Medical University (Shanghai), Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
Cheng
Hui-Lin
HL
Zhao
Xu-Dong
XD
Dai
Wei
W
Zhuang
Zong
Z
Wu
Yi
Y
Liu
Yong
Y
Shi
Ji-Xin
JX
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015687:Cell Hypoxia; D002540:Cerebral Cortex / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D016489:Head Injuries, Closed / Q000378:metabolism / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D009593:Nitroimidazoles / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics
D015415:Biomarkers; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009593:Nitroimidazoles; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C033815:pimonidazole