Melatonin Improves Vasogenic Edema via Inhibition to Water Channel Aquaporin-4 (AQP4) and Metalloproteinase-9 (MMP-9) Following Permanent Focal Cerebral Ischemia
Ai-Hua Lee,
Shih-Huang Tai,
Sheng-Yang Huang,
Li-Der Chang,
Liang-Yi Chen,
Yu-Ning Chen,
Hao-Hsiang Hsu,
E-Jian Lee
Affiliations
Ai-Hua Lee
Neurophysiology Laboratory, Neurosurgical Service, Departments of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
Shih-Huang Tai
Neurophysiology Laboratory, Neurosurgical Service, Departments of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
Sheng-Yang Huang
Neurophysiology Laboratory, Neurosurgical Service, Departments of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
Li-Der Chang
Neurophysiology Laboratory, Neurosurgical Service, Departments of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
Liang-Yi Chen
Neurophysiology Laboratory, Neurosurgical Service, Departments of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
Yu-Ning Chen
Neurophysiology Laboratory, Neurosurgical Service, Departments of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
Hao-Hsiang Hsu
Neurophysiology Laboratory, Neurosurgical Service, Departments of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
E-Jian Lee
Neurophysiology Laboratory, Neurosurgical Service, Departments of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
Background: The efficacy of melatonin in reducing vasogenic and cytotoxic edema was investigated using a model of permanent middle cerebral artery occlusion (pMCAO). Methods: Rats underwent pMCAO, followed by intravenous administration of either melatonin (5 mg/kg) or a vehicle 10 min post-insult. Brain infarction and edema were assessed, and Western blot analyses were conducted to examine the expression levels of aquaporin-4 (AQP4), metalloproteinase-9 (MMP-9), and the neurovascular tight-junction protein ZO-1 upon sacrifice. The permeability of the blood–brain barrier (BBB) was measured using spectrophotometric quantification of Evans blue dye leakage. Results: Compared to controls, melatonin-treated rats exhibited a significant reduction in infarct volume by 26.9% and showed improved neurobehavioral outcomes (p p p Conclusions: Therefore, melatonin offers neuroprotection against brain swelling induced by ischemia, possibly through its modulation of AQP4 and MMP-9 activities in glial cells and the extracellular matrix (ECM) during the early phase of ischemic injury.
