Effects of combination treatment of dexamethasone and melatonin on brain injury in intracerebral hemorrhage model in rats.
The study was performed to investigate the effect of combination therapy with melatonin and dexamethasone (DEX) on brain injury in intracerebral hemorrhage (ICH) model in rats. Compared to the control group, combination therapy group with melatonin (10 mg/kg) and DEX (0.025 mg/kg) significantly reduced the degree of (1) brain edema, (2) the permeability of blood brain barrier (measured by Evans blue), (3) Oxidative stress (evaluated by malondialdehyde assay), (4) cytokines expression (tumor necrosis factor-alpha and interleukin-1beta), and (5) apoptosis (measured by Bax and Bcl-2 expression). In addition, we have also clearly demonstrated that the combination therapy significantly ameliorated neurologic scores. Taken together, our results clearly indicated for the first time that strategies targeting multiple proinflammatory pathways may be more effective than a single effector molecule for the treatment of ICH.
Li
Zhi-qing
ZQ
Department of Neurosurgery, Shenyang Northern Hospital, Shenyang, China.
Liang
Guo-biao
GB
Xue
Yi-xue
YX
Liu
Yun-hui
YH
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003907:Dexamethasone / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D009460:Neurologic Examination; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D053583:Interleukin-1beta; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D003907:Dexamethasone; D009195:Peroxidase; D008550:Melatonin