Key result
Middle cerebral artery occlusion in rats led to increasingly chaotic microvascular flows in the ischemic penumbra over 4 hours, with up to 25% of capillaries showing flow reversal.
Why the study?
Neuroimaging studies in acute ischemic stroke suggest penumbral tissue is characterized by hypoperfusion and microvascular flow disturbances that strongly affect tissue outcome, but microscopic distribution changes remain unclear.
Microvascular flow disturbances, such as capillary stalls and flow reversals, progressively worsen in the ischemic penumbra and severely limit tissue oxygenation independently of macrovascular blood flow.
Evolving penumbral flow instability in rodent stroke models; hypothesis-generating for human microvascular-targeted therapies.
Acute ischemic stroke (AIS) is a frequent cause of death and adult disability. AIS patient management targets the ischemic penumbra: Hypoperfused, electrically silent brain tissue, which can be salvaged by restoring blood flow during the first, critical hours after symptom onset. Neuroimaging studies in AIS patients suggest that penumbral tissue is characterized not only by hypoperfusion, but also by microvascular flow disturbances that strongly affect tissue outcome. Here, we demonstrate that microvascular flows become increasingly chaotic in the ischemic penumbra in the hours after middle cerebral artery occlusion in a rat model of AIS. Biophysical models suggest that these disturbances are accompanied by increasing hypoxia in the absence of blood flow changes. Unlike findings in severe ischemia, pericyte constrictions do not appear to occlude penumbral capillaries. We propose that microvascular flow disturbances represent a critical feature of penumbral tissue, and a potential target for neuroprotective therapy after AIS.
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Iversen et al. (2023) studied Acute ischemic stroke (n=38). Middle cerebral artery occlusion (MCAo) vs. Control animals was evaluated on Microvascular flow disturbances (capillary transit time heterogeneity, RBC flow reversal and stalls). Middle cerebral artery occlusion in rats led to increasingly chaotic microvascular flows in the ischemic penumbra over 4 hours, with up to 25% of capillaries showing flow reversal.