Introduction
Structural integrity of the brain tissue during the acute phase following ischemic stroke does not necessarily imply recovery of function (NMR Biomed, 2000; 13: 361–370). In fact, little is known about the region-specific relationship between structural and functional integrities after stroke. Functional magnetic resonance imaging (fMRI) using pharmacological stimulation paradigms inducing a global brain response is a sensitive method to study functional changes in the rodent brain in vivo (MRI, 2002; 20: 447–454).
Methods
We measured changes in local cerebral blood volume (CBV), induced by systemic infusion of the GABAA antagonist bicuculline in ischemic mice following 30 minutes of intraluminal middle cerebral artery (MCA) occlusion, using magnetite nanoparticles as an intravascular contrast agent. T2- and diffusion weighted (DW) images, as well as fMRI were acquired at different time-points after reperfusion (24 hr, 72 hr and 7 days). Changes in CBV were analyzed in various brain areas.
Results
In response to bicuculline stimulation, region-specific increases in CBV were observed in the striatum, cortex and thalamus of control and sham-operated non-ischemic animals. In ischemic animals, on the other hand, functional response to bicuculline displayed a long-lasting reduction in the ischemic striatum and cortex, while structural integrity, as evidenced by T2 and DW signal hyperintensities, was compromised mainly in the striatum, but rarely in the cortex, even at three and seven days after lesioning (Fig. 1).
T2W, DWI and CBV maps acquired during 72 hr reperfusion period following period following 30 min MCAO.
Conclusions
a) bicuculine-induced global brain stimulation is a sensitive and informative method to characterize the functional recovery of post-ischemic mouse brain, b) as previously shown in rats, apparent anatomical integrity does not necessarily translate into functional integrity of certain brain structures in the mouse; on the other hand, an abnormal appearance of edematic tissue does not always imply compromised functional activity. The correlation of anatomical, metabolic and functional read-outs during different post-ischemic recovery periods can be further used to test various neuroprotective compounds for their ability to benefit the recovery of brain function.