Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury.
RatTBIWeight-drop / impact-accelerationSprague-DawleyMalen = n = 10 per group across six groups (control, mild, moderate…Stereotactic intracerebroventricular injection into the right lateral ventricle (coordinates -0.8 mm anteroposterior, 1.6 mm mediolateral, -4.0 mm dorsoventral from bregma)DAPT solution at 1 microgram per microlitre, dissolved in 0…30 minutes after injury
Model: Weight-drop craniocerebral injury through a 5 mm parietal bone window under 1% pentobarbital anaesthesia (30 mg/kg intraperitoneally); mild injury a 20 g hammer dropped 10 cm, moderate and severe injury a 40 g hammer dropped 15 cm or 25 cm respectively
Notch, Hes1 and Hes5 expression rose in proportion to injury severity. In severe injury, DAPT reduced Notch, Hes1 and Hes5 protein and mRNA, lowered the number of TUNEL-positive cells, decreased Bax, caspase-3 and caspase-9 and increased Bcl-2, reduced malondialdehyde and raised superoxide dismutas…
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