Acute ischemic stroke results from sudden decrease or loss of blood supply to an area of the brain, resulting in a coinciding loss of neurological function. The antioxidant action of melatonin is an important mechanism among its known effects to protective activity during ischemic/reperfusion injury. The focus of this research, therapeutic efficacy of melatonin on recovery of neurological function following long term treatment in ischemic brain injured rats. Male Sprague-Dawley rats (n=40; 8 weeks old) were divided into the control group, and MCAo groups (Vehicle, MT7 : MCAo+ melatonin injection at 7:00, MT19 : MCAo+melatonin injection at 19:00, and MT7,19 : MCAo+melatonin injection at 7:00 and 19:00). Rat body weight and neurological function were measured every week for 8 weeks. After 8 weeks, the rats were anesthetized with a mixture of zoletil (40 mg/kg) and xylazine (10 mg/kg) and sacrificed for further analysis. Tissues were then collected for RNA isolation from brain tissue. Also, brain tissues were analyzed by histological procedures. We elucidated that melatonin was not toxic in vital organs. MT7,19 was the most rapidly got back to mild symptom on test of neurological parameter. Also, exogenous melatonin induces both the down-regulation of detrimental genes, such as NOSs and the up-regulation of beneficial gene, including BDNF during long term administration after focal cerebral ischemia. Melatonin treatment reduced the loss of primary motor cortex. Therefore, we suggest that melatonin could be act as prophylactic as well as therapeutic agent for neurorehabilitative intervention.

ABSTRACT   INTRODUCTION   MATERIALS AND METHODS    Animals    Focal Cerebral Ischemia/Reperfusion Surgery    Melatonin Treatment    Measurement of Neurological Dysfunction    2% 2,3,5-Triphenyltetrazolium Chloride (TTC) Staining    H and E Staining    Gene Analysis    Statistical Analysis   RESULTS    Physiological General Feature of MCAo rats   DISCUSSION   REFERENCES

• Seunghoon(Department Rehabilitation Science in Interdisciplinary PhD Program, Graduate School of Inje University)
• Jinhee Shin(Department Physical Therapy, Graduate School of Inje University)
• Minkyung Lee(Department Physical Therapy, Graduate School of Inje University)
• Sang-Kil Lee(Cardiovascular and Metabolic Disease Center, College of Biomedical Science and Engineering)
• Sang-Rae Lee(National Primate Research Center, Korea Research Institute of Biotechnology)
• Kyu-Tae Chang(National Primate Research Center, Korea Research Institute of Biotechnology) Corresponding author
• Yonggeun Hong(Department Rehabilitation Science in Interdisciplinary PhD Program, Graduate School of Inje University, Department Physical Therapy, Graduate Shcool of Inje University, Cardiovascular and Metabolic Disease Center, College of Biomedical Science and Engineering, National Primate Research Center, Korea Research Institute of Biotechnology) Corresponding author