Details

Autor(en) / Beteiligte

• Zhou, Xiao-Ming
• Zhang, Xin
• Zhang, Xiang-Sheng
• Zhuang, Zong
• Li, Wei
• Sun, Qing
• Li, Tao
• Wang, Chun-Xi
• Zhu, Lin
• Shi, Ji-Xin
• Zhou, Meng-Liang

Titel

SIRT1 inhibition by sirtinol aggravates brain edema after experimental subarachnoid hemorrhage

Ist Teil von

• Journal of neuroscience research, 2014-06, Vol.92 (6), p.714-722

Ort / Verlag

United States: Blackwell Publishing Ltd

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Secondary brain injury following subarachnoid hemorrhage (SAH) is poorly understood. We utilized a rat model of SAH to investigate whether SIRT1 has a protective role against brain edema via the tumor suppressor protein p53 pathway. Experimental SAH was induced in adult male Sprague‐Dawley rats by prechiasmatic cistern injection. Brain SIRT1 protein levels were examined in the sham controls and in rats 6, 12, 24, 48, and 72 hr after SAH induction. The SIRT1 inhibitor sirtinol was administered by intracerebroventricular infusion. Neurological functions, blood–brain barrier (BBB) disruption, and brain water content were assessed. Endothelial cell apoptosis, caspase 3 protein expression, p53 acetylation, and matrix metalloproteinase‐9 (MMP‐9) activity were examined. Compared with the control, SIRT1 protein expression increased remarkably, reaching a maximum at 24 hr after SAH. Sirtinol treatment significantly lowered SIRT1 expression, accompanied by deteriorated neurologic function, BBB disruption, brain edema, increased endothelial cell apoptosis, and increased MMP‐9 gelatinase activity compared with the rats treated with vehicle only. Our results suggest that increased expression of endogenous SIRT1 may play a neuroprotective role against brain edema after SAH. © 2014 Wiley Periodicals, Inc.