Glibenclamide Attenuates Blood-Brain Barrier Disruption in Adult Mice after Traumatic Brain Injury.
Glibenclamide is a hypoglycemic drug that is widely used for the treatment of diabetes mellitus type 2 (DM II), but it also plays a protective role following injury to the central nervous system (CNS). However, the precise mechanisms underlying its neuroprotective actions remain to be elucidated. Therefore, the present study evaluated the effects of glibenclamide on the blood-brain barrier (BBB) in a mouse model of traumatic brain injury (TBI). In the present study, 86 adult male C57BL/6 mice were exposed to a controlled cortical impact (CCI) injury and then received glibenclamide (10 μg) for 3 days. Tight junction (TJ) protein levels, BBB permeability, and tissue hemoglobin levels were evaluated following the CCI injury. Additionally, a biaxial stretch injury was applied to cell cultures of bEnd.3 cells using the Cell Injury Controller II system to explore the mechanisms by which glibenclamide inhibits apoptosis-signaling pathways. Compared with the control group, glibenclamide-treated mice exhibited decreases in brain water content (p < 0.05), tissue hemoglobin levels (p < 0.05), and Evans Blue extravasation (p < 0.01) after the CCI injury. Glibenclamide primarily attenuated apoptosis via the JNK/c-jun signaling pathway and resulted in an elevation of stretch injury-induced ZO-1 expression in bEnd.3 cells (p < 0.01).Glibenclamide downregulated the activity of the JNK/c-jun apoptosis-signaling pathway which, in turn, decreased apoptosis in endothelial cells (ECs). This may have prevented the disruption of the BBB in a mouse model of TBI.
Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .
Zhi-Ming
ZM
Xu
Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .
Fang
F
Yuan
Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .
Ying-Liang
YL
Liu
Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .
Jun
J
Ding
Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China .
Heng-Li
HL
Tian
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D018696:Neuroprotective Agents; D005905:Glyburide
BBB; TBI; animal studies; apoptosis