Spatial and Temporal Assessment of Cerebral Blood Flow in a Novel Piglet Model of Neonatal Arterial Ischemic Stroke

Neonatal arterial ischemic stroke (NAIS) is associated with considerable pediatric morbidity and mortality but lacks effective treatment options compared to adult stroke, highlighting the need for clinically relevant translational models. This study aimed to develop a novel middle cerebral artery occlusion (MCAO) model in neonatal piglets with exceptional clinical relevance and the opportunity for long-term survival. Piglets were randomly assigned to undergo either MCAO (n=8) or sham surgery (n=6). MCAO was achieved by occluding MCAs using 7mm aneurysm clips via craniotomy. Laser speckle contrast imaging was used to measure changes in relative cerebral blood flow (rCBF) in three cortical regions (anterior cerebral artery territory, penumbra, and ischemic core). Open field testing was performed in a subset of piglets at baseline, 24h post-MCAO, and 48h post-MCAO. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was used to identify infarcts at 48h post-MCAO. By 10 minutes post-MCAO, the rCBF had risen approximately 22.4% in the ischemic core compared to immediately post-MCAO ( p <0.05), with the area of the core as a percentage of the ipsilateral hemisphere decreasing by 38%. Furthermore, MCAO piglets showed increased ipsiversive circling at 48h post-MCAO (16±4 vs 7.3±1.4 ipsiversive rotations, p <0.05) compared to baseline and higher infarct volumes compared to sham piglets (31.6±6.4%, p <0.01). Overall, our model creates a reproducible infarct with consistent neuromotor deficits, real-time assessment of rCBF dynamics, and long-term survival, thus offering insights that may inform the development of novel therapies and improve NAIS outcomes.