Neuroprotective effect of spiradoline and naloxone in focal cerebral ischemia: Promising behavioral and biochemical changes in Wistar rats.

ABSTRACT

Brain ischemia modulates endogenous opioids production and the expression of opioid receptors. The present investigations aim to determine the neuroprotective effect of Spiradoline and Naloxone, administered intraperitoneally, against carotid artery occlusion induced cerebral ischemia in adult male Wistar rats. The ischemic assessment was carried out by evaluation of behavioral (cognitive and sensorimotor), and biochemical (antioxidants, acetylcholinesterase, brain swelling and hemispheric water content) parameters. The groups included sham-operated control, vehicle control, spiradoline-treated and naloxone-treated rats. Carotid artery occlusion induced behavioral impairment as per 8-arm radial maze, elevated plus maze, sensorimotor deficits, free radical production and biochemical changes. The results revealed that spiradoline significantly (p<0.05) antagonized the cognitive and sensorimotor deficits, indicated by reduced working memory errors, increased transfer latency time, and neurologic scores on 24 h and day 7 after ischemia, while naloxone produced transient improvement. The drugs significantly (p<0.05) restored the levels of antioxidants, and acetylcholinesterase on day 7. The brain edema development was significantly antagonized by spiradoline while naloxone showed lesser improvement. The results implied that the opioid agonist spiradoline has better efficacy than opioid antagonist naloxone for brain stroke therapy at tested doses, and spiradoline may be used in future combination therapies as a neuroprotective drug.