Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats.

Abstract

We have previously shown that exogenous melatonin improves the preservation of the blood-brain barrier (BBB) and neurovascular unit following cerebral ischemia-reperfusion. Recent evidence indicates that postischemic microglial activation exaggerates the damage to the BBB. Herein, we explored whether melatonin mitigates the cellular inflammatory response after transient focal cerebral ischemia for 90 min in rats. Melatonin (5 mg/kg) or vehicle was given intravenously at reperfusion onset. Immunohistochemistry and flow cytometric analysis were used to evaluate the cellular inflammatory response at 48 hr after reperfusion. Relative to controls, melatonin-treated animals did not have significantly changed systemic cellular inflammatory responses in the bloodstream (P > 0.05). Melatonin, however, significantly decreased the cellular inflammatory response by 41% (P < 0.001) in the ischemic hemisphere. Specifically, melatonin effectively decreased the extent of neutrophil emigration (Ly6G-positive/CD45-positive) and macrophage/activated microglial infiltration (CD11b-positive/CD45-positive) by 51% (P < 0.01) and 66% (P < 0.01), respectively, but did not significantly alter the population composition of T lymphocyte (CD3-positive/CD45-positive; P > 0.05). This melatonin-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction and improved neurobehavioral outcome by 43% (P < 0.001) and 50% (P < 0.001), respectively. Thus, intravenous administration of melatonin upon reperfusion effectively decreased the emigration of circulatory neutrophils and macrophages/monocytes into the injured brain and inhibited focal microglial activation following cerebral ischemia-reperfusion. The finding demonstrates melatonin's inhibitory ability against the cellular inflammatory response after cerebral ischemia-reperfusion, and further supports its pleuripotent neuroprotective actions suited either as a monotherapy or an add-on to the thrombolytic therapy for ischemic stroke patients.

• Authors: Ming-Yang Lee, Yu-Hsiang Kuan, Hung-Yi Chen, Tsung-Ying Chen, Shur-Tzu Chen, Chien-Chih Huang, I-Ping Yang, Yun-Shang Hsu, Tian-Shung Wu, E-Jian Lee
• Journal: Journal of pineal research (J Pineal Res) Vol. 42 Issue 3 Pg. 297-309 (Apr 2007) ISSN: 0742-3098 [Print] England
• PMID: 17349029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Melatonin

Topics

• Animals
• Inflammation (drug therapy)
• Injections, Intravenous
• Ischemic Attack, Transient (drug therapy)
• Leukocytes (drug effects)
• Male
• Melatonin (administration & dosage)
• Microglia (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reperfusion