Background: Cerebral pulsatility index (PI) is used as a proxy for downstream vascular resistance in acute ischemic stroke in clinical studies, with PI measurements from the contralateral hemisphere serving as reference value1. We hypothesize that PI and cerebral blood flow changes occur in both hemispheres during acute ischemic stroke and aim to investigate these changes in a mouse model of transient acute ischemic stroke.
Methodology: Cerebral blood flow and PI before, during and after stroke-induction were measured using laser speckle contrast imaging in both brain hemispheres through bilateral cranial windows in five C57BL/6JRj male mice (age: 15-16 weeks). All animals received 10-13 training sessions for both handling2,3 and for head fixation to allow for cerebral blood flow imaging in awake mice, as anaesthesia with isoflurane affects cerebral arteries4. All surgeries were performed under inhalation of isoflurane (induction: 4 %, 100% O2, flow: 0.6 L/min; maintenance: 1,5%, 100% O2, flow: 0.4 L/min).
The middle cerebral artery (MCA) was accessed through a 2-3 mm craniotomy in the right temporal bone, and the MCA was gently compressed for 1 hour with two micropipettes5. Decrease in MCA blood flow was assessed in real-time to validate MCA-occlusion (MCA-O). Cerebral blood flow and PI were measured repeatedly at baseline (awake and anaesthetized mouse), during MCA-O and immediately after pipette retraction (anaesthetized mouse), and on daily follow-ups for seven days (awake mouse).
Data are presented as mean ± SD, and changes between the two MCA were analysed with paired t-test. Longitudinal changes in PI and cerebral blood flow were analysed with two-way repeated measures ANOVA and corrected for multiple comparisons with post-hoc Bonferroni test. Significant effects are defined as p< 0.05.
Results: There were no differences in PI between both MCA at baseline, during MCA-O and follow-up. There were no significant changes in PI for both MCAs over time during MCA-O. Changes in PI for the right MCA were observed during follow-up at 48h (0.15 ± 0.04 vs 0.21 ± 0.03, p=0.0004) and 96h (0.16 ± 0.03 vs 0.21 ± 0.03, p=0.0125) as compared to baseline.
Changes in PI for the left MCA were identified during follow-up at 48h (0.15 ± 0.02 vs 0.22 ± 0.01, p<0.0001) and 96h (0.17 ± 0.03 vs 0.22 ± 0.01, p=0.0053) as compared to baseline.
Blood flow index did not change between both MCA at baseline and during follow-up. There were no changes in blood flow index over time at baseline and follow-up (awake). Blood flow index between the right and left MCA (107.4 ± 45.6 vs 455.2 ± 215.3, p <0.003) was significantly different during MCA-O. Significant changes in blood flow index over time were observed in the right MCA between baseline (anaesthetized) and during MCA-O (360 ± 148.9 vs 107.4 ± 45.6, p<0.0007).
Conclusion: There were no differences between PI in both MCA before, during and after MCA-O. PI from both MCA were reduced during follow-up, as compared to baseline. Blood flow index did not differ between the two MCAs at baseline and during follow-up, except during MCA-O.