Spatial and Longitudinal Assessment of Cerebral Perfusion in A Novel Piglet Model of Neonatal Arterial Ischemic Stroke

Background: Neonatal arterial ischemic stroke (NAIS) is a significant pediatric health problem associated with long-term morbidity. LMAs are a network of pial arteriole-to-arteriole anastomotic connections between two major cerebral vessels supplying two major cortical territories, such as the middle cerebral artery (MCA) and the anterior cerebral artery (ACA). In the setting of large vessel occlusion (e.g., stroke), blood flow in LMAs can reverse direction, providing retrograde perfusion to ischemic but salvageable tissue (penumbra). Few studies have investigated the role of LMAs in the pathophysiology of NAIS. In addition, the lack of large animal models of NAIS makes translational studies in the NAIS field difficult, particularly with respect to the development and testing of therapeutics. Hypothesis: MCAO in neonatal piglets will be associated with an increase in relative cerebral blood flow (rCBF) in the penumbra. Methods: Fourteen Yorkshire piglets were assigned to either the MCAO group (n=8) or the sham (n=6). Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2), and body temperature (temp) were monitored during surgery. A microsurgical craniotomy was used to approach and occlude the MCAs with 7mm aneurysm clips. Laser speckle contrast imaging (LSCI) was used to measure rCBF before, immediately after, and 10 min post-MCAO. Open field tests (OFT) assessed neuromotor behavior 1 d before surgery and at 24 and 48 h post-MCAO. Infarction volumes were measured via 1% TTC staining at 48 h after MCAO. Results: No significant differences were observed in the basic vital parameters between the MCAO and sham groups. rCBF in the MCAO group reduced significantly (p<0.0001, compared with sham surgery group) in all three regions (ACA, penumbra, and ischemic core) at immediately post-MCAO (-52.3, -67.9, and -68.1% respectively), compared to baseline. At 10 min post MCAO, CBF in the ACA region showed a 35% increase compared to immediately post MCAO, and there was no significant difference (p=0.07) compared with sham surgery group. CBF at penumbra the region showed a 26% increase compared with same region immediately post MCAO. OFT showed increased circling behavior at 48 hours post-MCAO (rotations: MCAO vs Sham: 23±9 vs 12±2). The infarct volume in the MCAO group was 36.0±17.8% of the hemisphere volume, significantly higher than the sham group (0%).Conclusions: This neonatal piglet MCAO model produced cerebral infarction with high reproducibility. LSCI provided a reliable, spatial and longitudinal assessment of CBF dynamics, confirming successful MCAO. Furthermore, in the MCAO group, blood flow decreased immediately after clip placement and then partially recovered at 10 min, suggesting functional recruitment of LMAs. In addition, this model produced a phenotype consistent with MCA stroke demonstrated in prior studies in other species. These characterizations suggest that our novel neonatal piglet MCAO model provides a reliable and reproducible platform for studying neonatal stroke, offering insights into CBF dynamics, ischemic injury, and potential therapeutic strategies for NAIS. This study was supported by internal funding from the Department of Anesthesiology and Critical Care Medicine at Johns Hopkins University. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.