Background: Neonatal arterial ischemic stroke (NAIS) is caused by large arterial occlusion in the first 28 days of life and often leads to long-term disability, including cerebral palsy and epilepsy. There are currently no approved treatments. Understanding cerebral blood flow dynamics after neonatal stroke is critical for identifying new therapeutic targets. In the present study, we used our clinically relevant piglet model of middle cerebral artery occlusion (MCAO) to trial the impact of MAP augmentation with phenylephrine (PE), a safe and clinically available pressor agent. The overall goal of the study was to assess changes in perfusion and size of ischemic territory following MCAO with and without PE treatment. Methods: 16 piglets (5.88 +/- 0.35 days) were randomly assigned to undergo either MCAO alone (control, n=8) or MCAO followed by PE administration to raise MAP by 20% (PE, n=8) to assess changes in blood flow and area of ischemic region. Blood flow was measured using laser speckle contrast imaging (LSCI) of the entire exposed cortex, as well as within the ischemic penumbra and core. LSCI data were recorded every hour for 3 hours post-MCAO. Core and penumbra areas were quantified to assess ischemic progression. In a separate cohort (n=12), pial, mesenteric and intrarenal resistance vessels were isolated for wire myography to compare responsiveness to PE, norepinephrine, epinephrine, and dopamine. Results: MCAO produced an acute reduction in relative cerebral blood flow (rCBF) in both groups from baseline (68.7% +/- 1.6% PE vs. 70.4% +/- 1.2% control). PE infusion (1 to 4 µg/kg/min) increased MAP by ~20% and significantly improved core perfusion at all time points (increase of 14.8 +/- 2.7% at 1hr, 17.0 +/- 3.5% at 2hr, 16.6 +/- 4.3% at 3hr, p< 0.05). In comparison, there was no significant change observed in perfusion to core area in the control group (69.1%, 69.3% and 65.9% at 1hr, 2hr, and 3hr, respectively). MCAO induced a large ischemic core in both groups (48.6% with PE vs. 45.7% in control) at 0hr. After administration of PE, the core area significantly decreased compared to control (decrease of 27.1% at 1hr, p< 0.01; 27.9% at 2hr, p< 0.01 and 18.5% at 3hr, p< 0.05). The area of the penumbra significantly increased in PE group (increase of 14.5% at 1hr, p< 0.05; 18.4% at 2hr, p< 0.01 and 14.8% at 3hr, p< 0.05) post-MCAO. Wire myography showed PE and norepinephrine had a better cerebral profile, causing less pial arteriole constriction than in mesenteric or intrarenal arteries. Conclusions: PE administration increased rCBF to the core compared to baseline post- MCAO and reduced ischemic core area with a concomitant expansion of the penumbral region. PE also demonstrated a favorable cerebral profile, causing less pial constriction than in mesenteric or renal arteries by wire-myography. These findings suggest that PE-induced MAP augmentation may be a viable therapy to preserve at- risk but viable brain regions during the acute phase of MCAO. Future studies should examine the dose-response relationship between incremental increases in MAP and cerebral perfusion in the ischemic brain, the effect of phenylephrine on ischemic cerebral vessels, and the role of autoregulation. This abstract was presented at the American Physiology Summit 2026 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.
Hong et al. (Fri,) studied this question.