Validity of Laser Doppler Flowmetry in Predicting Outcome in Murine Intraluminal Middle Cerebral Artery Occlusion Stroke

Abstract

Background—Laser Doppler flowmetry (LDF) can reliably reflect brain perfusion in experimental stroke
by monitoring both the degree and the duration of relative regional cerebral blood flow (rCBF). Variation in
rCBF was continuously monitored in 68 mice undergoing middle cerebral artery occlusion (MCAO) and 25
mice undergoing sham-operation and documented as LDF (%). Transcranial LDF changes in the territory of
right middle cerebral artery during MCAO procedure were correlated with corrected infarct volume (CIV)
and neurological deficit score (NDS).
Methods—Ninety-three C57BL/6 mice (Harlan Laboratories, Indianapolis, IN) between 9 and 11 weeks
old were randomly selected and assigned to either MCAO for 45 minutes (n = 68) or sham group (n = 25).
Ischemia was induced using the transient intraluminal filament model of MCAO based on Koizumi’s
method and transcranial LDF was used to measure CBF during the procedure. Neurological deficits were
measured at 2 and 23 hours after MCA reperfusion with NDS and 2% triphenyltetrazolium chloride (TTC)
staining of carefully dissected brains was performed at 23 hours after reperfusion to determine infarct area.
Results—After common carotid artery occlusion (CCAO), there was a negative association between LDF
drop from base line and NDS at 2 hours (r = −0.43, P = 0.038) and 23 hours (r = −0.61, P = 0.003). Also, a
negative correlation was noted between MCA reperfusion LDF and NDS at 23 hours (r = −0.53, P =
0.001). Moreover, post-MCA reperfusion LDF had a positive association with initial CCAO LDF (r =
0.761, P = 0.000) and MCA occlusion LDF (r = 0.31, P = 0.036) in predicting neurological outcome. NDS
at 23 hours corresponded well with the infarct volume (r = 0.31, P = 0.005).
Conclusions—Greater augmentation of rCBF after MCA reperfusion was associated with improved neurological deficit scoring. Interestingly, greater reduction of regional cerebral blood flow after CCAO was
also associated with improved neurological outcomes. The favorable neurological outcome is possibly due
to interplay of factors such as vascular reserve, collaterals, and autoregulation mechanisms. We propose
LDF changes as an additional noninvasive prognosticator of stroke outcome in the setting of experimental
brain ischemia.