Evolution of blood-brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies

Blood-brain barrier (BBB) strictly controls matter exchange between blood and brain, and severely limits brain penetration of systemically administered drugs, resulting in ineffective drug therapy of brain diseases. However, during the onset and progression of brain diseases, BBB alterations evolve inevitably. In this review, we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer's disease, Parkinson's disease, epilepsy, stroke, traumatic brain injury and brain tumor. The advances on optimization of small molecules for BBB crossing and non-systemic administration routes (

Effect of propofol anesthesia on expression of β-secretase 1 and content of anyloid beta protein 1-42 in neonatal rat hippocampus / 中华麻醉学杂志

Objective To investigate the effect of propofol anesthesia on the expression of β-secretase 1 (BACE1) and content of anyloid beta protein 1-42 (Aβ1-42) in the neonatal rat hippocampus.Methods Ninety Sprague-Dawley rats,aged 7 days,weighing 12-16 g,were randomly divided into 3 groups ( n =30 each):control group (group C),single dose of propofol anesthesia group (group SP),and repeated doses of propofol anesthesia group (group RP).Group C received intraperitoneal normal saline 7.5 ml/kg once a day for 7 consecutive days.Group SP received normal saline 7.5 ml/kg once a day for 6 consecutive days and propofol 75 mg/kg on 7th day.Group RP received propofol 75 mg/kg once a day for 7 consecutive days.Six rats in each group were chosen at 15 min after the end of injection on 7th day and blood samples were taken from the left ventricle for determination of the blood glucose level and for blood gas analysis.Eight animals in each group were sacrificed on 1st,3rd and 7th day after the end of injection on 7th day to determine the expression of BACE1 (using Western blot) and content of Aβ1-42 in the hippocampus (by ELISA).Results Compared with groups C and SP,the expression of BACE1 was up-regulated and the content of Aβ1-42 was significantly increased at each time point in group RP ( P ＜ 0.01 ).There was no significant difference in the expression of BACE1 and content of Aβ1-42 at each time point between groups C and SP ( P ＞ 0.05).Conclusion Repeated doses of propofol up-regulate the expression of BACE1 and increase the content of Aβ1-42 in neonatal rat hippocampus,which may be one of the mechanisms by which propofol leads to long-term cognitive dysfunction.Single dose of propofol does not have the effect.