D-allose protects the blood brain barrier through PPARγ-mediated anti-inflammatory pathway in the mice model of ischemia reperfusion injury.
Our early experiments confirmed that D-allose was closely involved in the blood brain barrier (BBB) protection from ischemia reperfusion (IR) injury, but the regulatory mechanism is not fully defined. In this study, we aimed to investigate the role of D-allose in the protection of BBB integrity and the relevant mechanisms involved in the mice model of middle cerebral artery occlusion and reperfusion (MCAO/Rep). D-allose was intravenously injected via a tail vein (0.2mg/g and 0.4mg/g, 1h before ischemia), GW9662 was intraperitoneal injected to the mice (4mg/kg) before inducing ischemia 24h. Pretreatment with D-allose ameliorated the neurological deficits, infarct volume and brain edema in brains of MCAO/Rep mice. D-allose inhibited cell apoptosis in the mice model of MCAO/Rep. We observed that D-allose remarkably decreased BBB permeability and prevented the reduction of ZO-1, Occludin and Claudin-5 in mice brains with MCAO/Rep injury. D-allose also repressed the levels of TNF-α, NF-κB, interleukin (IL)-1β and IL-8 in inflammatory responses. The increases of intercellular adhesion molecular-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and CD11b/CD18 were significantly inhibited by D-allose during the MCAO/Rep injury. And D-allose decreased the L-selectin and P-selectin levels after MCAO/Rep. Moreover, D-allose induced up-regulation of peroxisome proliferator-activated receptor γ (PPARγ), and down-regulation of TNF-α and NF-κB after MCAO/Rep, which were abolished by utilization of GW9662. In conclusion, we provided evidences that D-allose may has therapeutic potential against brain IR injury through attenuating BBB disruption and the inflammatory response via PPARγ-dependent regulation of NF-κB.
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.15 Changle West Road, Xincheng District, Xi'an 710032, Shaanxi, China.
Tao
T
Huang
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.15 Changle West Road, Xincheng District, Xi'an 710032, Shaanxi, China.
Dakuan
D
Gao
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.15 Changle West Road, Xincheng District, Xi'an 710032, Shaanxi, China.
Yue
Y
Hei
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.15 Changle West Road, Xincheng District, Xi'an 710032, Shaanxi, China.
Xin
X
Zhang
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.15 Changle West Road, Xincheng District, Xi'an 710032, Shaanxi, China.
Xiaoyan
X
Chen
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.15 Changle West Road, Xincheng District, Xi'an 710032, Shaanxi, China. Electronic address: zhoufeishaanxi@163.com.
Zhou
Z
Fei
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D047495:PPAR gamma / Q000378:metabolism*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D016328:NF-kappa B; D018696:Neuroprotective Agents; D047495:PPAR gamma; C002055:allose; D005947:Glucose
BBB Permeability; D-Allose; IR Injury; PPARγ; TNF-α