Noninvasive and Tran sient Blood - Brain

The spatio-tem po ral na ture of fo cused ul tra sound-in duced blood-brain bar rier (BBB) open ing as a brain drug de liv ery method was in ves ti gated in Alz hei mer’s dis ease model mice. The left hip po cam pus of trans gen ic (APP/PS1, n = 3) and nontransgenic (n = 3) mice was sonicated (fre quency: 1.525 MHz, peak-neg a tive pres sure: 600 kPa, pulse length: 20 ms, duty cy cle: 20%, du ra tion: 1 min) in vivo, through their in tact skin and skull, af ter in tra ve nous in jec tion of microbubbles (SonoVue; 25 μl). Se quen tial, high-field MR im ages (9.4 Tesla) were ac quired be fore and af ter in jec tion of gad o lin ium (OmniscanTM; 0.75 ml, mo lec u lar weight: 573.7 Da) on two sep a rate days for each mouse. Gad o lin ium de pos its through the ul tra sound-in duced BBB open ing in the left hip po cam pus re vealed sig nif i cant con trast-en hance ment in the MRI. On the fol low ing day, MRI re vealed sig nif i cant BBB clo sure within the same re gion. How ever, the BBB open ing ex tent and BBB clos ing timeline var ied in dif fer ent re gions within the same sonicated lo ca tion. This in di cates that open ing and clos ing were de pend ent on the brain re gion tar geted. No sig nif i cant dif fer ence in BBB open ing or clos ing be hav iors was ob served be tween the APP/PS1 and the nontransgenic mice. In con clu sion, a BBB-im per me able mol e cule was noninvasively, tran siently and reproducibly de liv ered to the hip po cam pus of Alz hei mer’s APP/PS1 mice.