Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Role of the Nrf2-ARE pathway in early brain injury after experimental subarachnoid hemorrhage.

Authors: Chen, G  Fang, Q  Zhang, J  Zhou, D  Wang, Z 
Citation: Chen G, etal., J Neurosci Res. 2011 Apr;89(4):515-23. doi: 10.1002/jnr.22577. Epub 2011 Jan 21.
Pubmed: (View Article at PubMed) PMID:21259333
DOI: Full-text: DOI:10.1002/jnr.22577

The nuclear factor erythroid 2-related factor 2 and antioxidant-response element (Nrf2-ARE) pathway is a key regulator for modulating inflammation and oxidative damage, which are involved in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Previous studies have demonstrated that Nrf2-ARE pathway play neural protective roles in traumatic brain injury, cerebral ischemia, and intracerebral hemorrhage models; however, it has not been investigated whether, and to what degree, the Nrf2-ARE pathway is induced by SAH, and the role of the Nrf2-ARE pathway in development of EBI following SAH remains unknown. Experiment 1 sought to investigate the time course of Nrf2-ARE activation in the cortex in the early stage of SAH. In experiment 2, we assessed the effect of sulforaphane (SUL; a specific Nrf2 activator) on regulation of the Nrf2-ARE pathway in the SAH model and evaluated the impact of SUL on EBI after SAH. The rat SAH model was used injection of 0.3 ml fresh arterial, nonheparinized blood into the prechiasmatic cistern over 20 sec. As a result, Nrf2 and its target gene product, heme oxygenase-1 (HO-1), were up-regulated in the cortex after SAH and peaked at 24 hr post-SAH. After intraperitoneal SUL administration, the elevated expression of Nrf2-ARE-related factors such as Nrf2, HO-1, NAD(P)H:quinone oxidoreductase 1 (NQO1), and glutathione S-transferase-alpha1 (GST-alpha1) was detected in the cortex at 48 hr following blood injection. In the SUL-treated group, early brain damage such as brain edema, blood-brain barrier (BBB) impairment, cortical apoptosis, and motor deficits was significantly ameliorated compared with vehicle-treated SAH rats. Our results suggest that the Nrf2-ARE pathway is activated in the brain after SAH, playing a beneficial role in EBI development, possibly through inhibiting cerebral oxidative stress by inducing antioxidant and detoxifying enzymes.

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
RGD Object Information
RGD ID: 5133235
Created: 2011-06-08
Species: All species
Last Modified: 2011-06-08
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.