Carvacrol alleviates cerebral edema by modulating AQP4 expression after intracerebral hemorrhage in mice.
Carvacrol is a natural compound extracted from many plants of the family Lamiaceae. Previous studies have demonstrated that carvacrol has potential neuroprotective effects in central nervous system diseases such as Alzheimer's disease and cerebral ischemia. In this study, we investigated the preclinical effect of carvacrol on cerebral edema after intracerebral hemorrhage (ICH) using a bacterial collagenase-induced ICH mouse model. Mice were randomly divided into sham (n=43), vehicle-treated (n=51), and carvacrol-treated groups (n=101). In carvacrol-treated group, carvacrol was administrated to mice at 0h, 1h, or 3h after ICH induction. Carvacrol was injected intraperitoneally with single doses of 10, 25, 50, or 100mg/kg. Neurologic dysfunctions, brain water content, aquaporins (AQPs) mRNAs level and AQP4 protein expression in the perihematomal area were evaluated post ICH. Our results showed that carvacrol administration improved neurological deficits after day 3 following ICH (p<0.05). Carvacrol reduced cerebral edema and Evans Blue leakage at day 3 (p<0.05). We also found that carvacrol treatment decreased AQP4 mRNA in a dose-dependent manner at 24h. Furthermore, AQP4 protein expression in the perihematomal area was reduced by carvacrol significantly at day 3 after ICH (p<0.05). Our findings suggest that carvacrol may exert its protective effect on ICH injury by ameliorating AQP4-mediated cerebral edema.
Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
Zhihong
Z
Zhong
Baofeng
B
Wang
Minchao
M
Dai
Yuhao
Y
Sun
Qingfang
Q
Sun
Guoyuan
G
Yang
Liuguan
L
Bian
D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D000081007:Cymenes; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D000081007:Cymenes; D039821:Monoterpenes; D018696:Neuroprotective Agents; C073316:carvacrol
AQP; Aquaporin-4; BBB; Carvacrol; Cerebral edema; ICH; Intracerebral hemorrhage; aquaporin; blood–brain barrier; intracerebral hemorrhage