1. Tempol alleviates intracerebral hemorrhage-induced brain injury possibly by attenuating nitrative stress.
- Author
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Wanyong Y, Zefeng T, Xiufeng X, Dawei D, Xiaoyan L, Ying Z, and Yaogao F
- Subjects
- Animals, Antioxidants pharmacology, Apoptosis drug effects, Apoptosis physiology, Blood-Brain Barrier drug effects, Blood-Brain Barrier metabolism, Blood-Brain Barrier pathology, Brain pathology, Brain physiopathology, Brain Edema drug therapy, Brain Edema etiology, Brain Edema pathology, Brain Edema physiopathology, Brain Injuries etiology, Brain Injuries pathology, Brain Injuries physiopathology, Cerebral Hemorrhage complications, Cerebral Hemorrhage pathology, Cerebral Hemorrhage physiopathology, Collagenases, Disease Models, Animal, Male, Random Allocation, Rats, Sprague-Dawley, Spin Labels, Tyrosine analogs & derivatives, Tyrosine metabolism, Zonula Occludens-1 Protein metabolism, Brain drug effects, Brain Injuries drug therapy, Cerebral Hemorrhage drug therapy, Cyclic N-Oxides pharmacology, Neuroprotective Agents pharmacology
- Abstract
Intracerebral hemorrhage (ICH)-induced brain injury leads to irreversible disruption of the blood-brain barrier (BBB) and fatality brain edema with massive cell death. Although secondary damage could, in principle, be preventable, no effective treatment approaches currently exist for patients with ICH. Tempol, a catalytic scavenger of peroxynitrite (ONOO)-derived free radicals, has been proven to ameliorate brain injury in several types of brain insults. This study aims to investigate the potential neuroprotective effect of tempol after ICH and to explore the underlying mechanisms. Collagenase-induced ICH was performed in rats. Tempol was administered immediately after ICH. The effects of tempol on ICH were evaluated by assessing neurological deficits, BBB permeability, brain edema, and apoptotic cell death. The mechanisms of action of tempol, with its clear ability on the derivative of ONOO [3-nitrotyrosine (3-NT), ONOO, and its derivative-mediated nitration marker] and expression of tight junction protein [zonula occludens-1 (ZO-1)], were also investigated. Perihematomal 3-NT increased significantly following ICH and expressed around vessels accompanied by reduced and discontinuous expression of ZO-1. Tempol treatment significantly suppressed 3-NT formation and preserved ZO-1 levels, and led to improvement in neurological outcomes and reduction of BBB leakiness, brain edema, and apoptosis. In conclusion, tempol has neuroprotective potential in experimental ICH and may help combat ICH-induced brain injury in patients.
- Published
- 2015
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