RT Journal Article
SR Electronic
T1 Blood–Brain Barrier Disruption in Preclinical Mouse Models of Stroke Can Be an Experimental Artifact Caused by Craniectomy
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0343-22.2022
DO 10.1523/ENEURO.0343-22.2022
VO 9
IS 5
A1 Che-Wei Liu
A1 Eric Yuhsiang Wang
A1 Hwai-Lee Wang
A1 Kate Hsiurong Liao
A1 Hsiao-Yun Chen
A1 Hank Szuhan Chen
A1 Ted Weita Lai
YR 2022
UL http://www.eneuro.org/content/9/5/ENEURO.0343-22.2022.abstract
AB The pathophysiological features of ischemia-related blood–brain barrier (BBB) disruption are widely studied using preclinical stroke models. However, in many of these models, craniectomy is required to confirm arterial occlusion via laser Doppler flowmetry or to enable direct ligation of the cerebral artery. In the present study, mice were used to construct a distal middle cerebral artery occlusion (dMCAO) model, a preclinical stroke model that requires craniectomy to enable direct ligation of the cerebral artery, or were subjected to craniectomy alone. dMCAO but not craniectomy caused neurodegeneration and cerebral infarction, but both procedures induced an appreciable increase in BBB permeability to Evans blue dye, fluorescein, and endogenous albumin but not to 10 kDa dextran-FITC, leading to cerebral edema. Using rats, we further showed that BBB disruption induced by craniectomy with no evidence of dural tearing was comparable to that induced by craniectomy involving tearing of the dura. In conclusion, our data demonstrated that craniectomy can be a major contributor to BBB disruption and cerebral edema in preclinical stroke models. The implications of this experimental artifact for translational stroke research and preclinical data interpretation are discussed.