Anemonin Alleviates Nerve Injury After Cerebral Ischemia and Reperfusion (I/R) in Rats by Improving Antioxidant Activities and Inhibiting Apoptosis Pathway

• Published in: Journal of molecular neuroscience Vol. 53; no. 2; pp. 271 - 279
• Main Authors: Jia, Dong, Han, Bin, Yang, Shaowei, Zhao, Junying
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2014; Springer Nature B.V
• Subjects: Animals; Antioxidants; Apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Carotid arteries; Catalase - metabolism; Cell Biology; Free radicals; Furans - pharmacokinetics; Furans - pharmacology; Furans - therapeutic use; Glutathione - metabolism; Hospitals; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - metabolism; Ischemia; Male; Malondialdehyde - metabolism; Neurochemistry; Neurology; Neuroprotective Agents - pharmacokinetics; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Neurosurgery; Proteomics; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism; Superoxide Dismutase - metabolism; Veins & arteries; Oxidative stress; Neuroprotection; Cerebral ischemia/reperfusion injury; Blood-brain barrier; Anemonin; Apoptosis
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-013-0217-z

In the present study, we aimed at evaluating the potential neuroprotective effect and the underlying mechanism of anemonin against cerebral ischemia and reperfusion (I/R) injury. Anemonin was administered to rats by the intraperitoneally (i.p.) route once daily for 7 days before middle cerebral artery occlusion (MCAO). Focal cerebral ischemia was induced by 90 min of MCAO followed by 24 h of reperfusion. After that, animals were sacrificed by decapitation, brain was removed, and various biochemical estimations, neurological status, and assessment of cerebral infarct size were carried out. MCAO followed by 24 h of reperfusion caused a significant increase in infarct size, neurological deficit score, malondialdehyde (MDA) content, reactive oxygen species (ROS) level, and DNA fragmentation, as well as a decrease in the activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and Na + , K + -ATPase in the brain. Furthermore, elevated Bax expression, increased caspase-3 cleavage, and decreased Bcl-2 expression were observed in nontreated rats in response to focal cerebral I/R injury. However, pretreatment with anemonin significantly reversed these levels of biochemical parameters, reduced cerebral infarct size, and improved the neurologic score in cerebral ischemic animals. Additionally, a wide distribution of anemonin in plasma and brain tissues and the brain-to-plasma partition coefficient (Ri) ratio of 0.7 at 90 min indicated that this compound could penetrate the blood-brain barrier (BBB). These results showed that pretreatment with anemonin provided a significant protection against cerebral I/R injury in rats by, at least in part, its antioxidant action and consequent inhibition of apoptosis.