Imaging Reveals the Focal Area of Spreading Depolarizations and a Variety of Hemodynamic Responses in a Rat Microembolic Stroke Model

Abstract

Spreading depolarizations (SDs) occur in stroke, but the spatial association between SDs and the corresponding hemodynamic changes is incompletely understood. We applied multimodal imaging to visualize the focal area of selected SDs, and hemodynamic responses with SDs propagating over the ischemic cortex. The intracarotid infusion of polyethylene microspheres (d ¼ 45 to 53 mm) produced multifocal ischemia in anesthetized rats (n ¼ 7). Synchronous image sequences captured through a cranial window above the frontoparietal cortex revealed: Changes in membrane potential (voltage-sensitive (VS) dye method); cerebral blood flow (CBF; laser speckle contrast (LSC) imaging); and hemoglobin (Hb) deoxygenation (red intrinsic optical signal (IOS) at 620 to 640 nm). A total of 31 SD events were identified. The foci of five SDs were seen in the cranial window, originating where CBF was the lowest (56.9±9%), but without evident signs of infarcts. The hyperemic CBF responses to propagating SDs were coupled with three types of Hb saturation kinetics. More accentuated Hb desaturation was related to a larger decrease in CBF shortly after ischemia induction. Microsphere-induced embolization triggers SDs in the rat brain, relevant for small embolic infarcts in patients. The SD occurrence during the early phase of ischemia is not tightly associated with immediate infarct evolution. Various kinetics of Hb saturation may determine the metabolic consequences of individual SDs.

Characterization of Intrinsic Optical Signal during Spreading Depolarization

“…Also, different propagation patterns of SD are observed in OIS. Bere et al using OIS in multi-focal stroke model in rats found that some SD waves gradually got extinguished and some SD waves might avoid the cortical region with lowest perfusion within the field of view during the propagation [34]. Santos et al detected diverse expansion patterns of SD with OIS in the cortex of swine: spiral wave, reverberating wave, and collision of two waves ( Figure 5) [16].…”

“…However, in pathological states, such as reduced perfusion pressure and ischemia, SD may trigger spreading ischemia and are owing to changes in light scattering, blood volume, and hemoglobin and cytochrome oxidation state. OIS is particularly appropriate for studying SD, because 1) a large-scale cerebral cortex can be studied simultaneously and numerous timepoints can be got over time as SD waves propagate; 2) OIS is able to provide information about propagating patterns of SD [16]; 3) OIS in multi-wavelength studies can correlate perfusion-related changes to electrophysiological changes of SD [17]; 4) it is important to identify the optical profile of SD, since OIS studies involving seizure, electrical stimulation, or mechanical perturbation of the cortex can inadvertently induce SD. In the past few years, OIS has been used to study SD in normal and pathological conditions [18].…”

The impact of aging on spreading depolarization in the intact and ischemic rat brain

“…In the present study, the longer duration of SD in the ischemic brain is attributed to the collective, lower rate of depolarization and repolarization, rather than the prolongation of complete depolarization itself 65 . 67 .…”

“…Ischemia shifts this balance toward the domination of the initial vasoconstrictive (hypoemic) element of the pattern, possibly as a function of decreasing perfusion pressure 28,65 . Matching this concept, we have identified 6 types of CBF kinetics ranging from dominating hyperemia to prolonged cortical spreading ischemia with intermediate forms.…”

Live, optical experimental neuroimaging reveals variations of the cerebral blood flow response to ischemic spreading depolarization

“…At present, the deficiency of the SD-associated CBF response is accepted to mediate neurodegeneration, because the insufficient CBF response sustains the state of depolarization and delays repolarization by depriving the tissue at risk of essential nutrients required to maintain ionic balance across neuronal cell membranes [14,32]. Baseline CBF (100%) is given as a horizontal line [34].…”