The predictive value of peri-infarct flow transients in focal brain ischemia

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Animal studies havebeen shown that spreading depolarizations(SD)play an importantrolein lesion progression during focal ischemia. Therefore SDs might serve as biomarkers of injury progressin ischemic stroke and in other SD related disordersin order to overcome translational roadblocks. Electrophysiological recordings of SDs havealreadybeenperformedin human studies, where the patient’scondition requirescraniotomy (for example subarachnoidhaemorrhage, malignant middle cerebral artery infarctionandsevere traumatic brain injury).However, anon-invasive, extracranialmonitoring of SDs would allow investigators to enroll a largerpatient population (all the patients with ischemic stroke and minor head trauma) immediately after the injury onset into the studies. The limitationsof extracranial recording of SDs turn the interest intomonitoring alternativebiomarkerssuch as peri-infarct flow transients(PIFTs)whichare the hemodynamical correlatesof SDsin stroke. The aim of this thesis was to investigate if the parameters of the PIFTs (number and the amplitudes) alone or combined with other flow parameters(intra-ischemic flow, level of reperfusion) collected by laser Doppler can predict histological outcomein experimental ischemic stroke.We hypothesizedalso that the amplitude and the morphology of flow transients show regional heterogeneity and therefore it can be helpful in distinguishing the ischemic core, penumbra and peri-ischemic area. We first determined the coupling rate between the DC deflections and PIFTs in amodel of filament occlusion (n=32) andfound that 93 % of the PIFTs recorded by an LD probe are tightlycoupled to DC deflections recordedby epidural silver chloride electrodes. The post hoc analysis of filament occluded animals (n=55) revealed that the combination of intra-ischemic blood flow and the number of PIFTs together is a good, earlypredictor ofhistological outcome. The spatial distribution of the amplitudes and the morphology were analyzed both inthefilament occlusionmodel(n=10)andin thephotochemically induced distal occlusion of the middle cerebral artery(n=8).We found thatlower residual flow, smaller amplitudes anda higher percentage of hypoperfusive flow transients is characteristic for penumbral areas, especiallycloser to the core. Ahigher residual blood flow andamplitude of flow transients along with alarger percentage ofhyperemicand hyperemia dominant biphasicflow transients indicatesperi-ischemic area.We conclude that PIFTs arepotential biomarkersin human studies.

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