Efficacy Assessment of Cerebral Perfusion Augmentation through Functional Connectivity in an Acute Canine Stroke Model.

Abstract

Background and purpose: Ischemic stroke disrupts functional connectivity within the brain's resting-state networks (RSNs), impacting recovery. This study evaluates the effects of norepinephrine and hydralazine (NEH), a cerebral perfusion augmentation therapy, on RSN integrity in a hyperacute canine stroke model.

Materials and methods: Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Postocclusion, the treatment group received intra-arterial norepinephrine (0.1-1.52 µg/kg/min, adjusted for 25-45 mm Hg above baseline mean arterial pressure) and hydralazine (20 mg). Resting-state fMRI (rs-fMRI) data were acquired with a 3T scanner by using a blood oxygen level dependent-EPI sequence (TR/TE = 1400 ms/20 ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm full width at half maximum), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis and weighted whole-brain ROI-to-ROI connectome, pre- and post-MCAO.

Results: NEH therapy significantly maintained connectivity post-MCAO in the higher-order visual and parietal RSNs, as evidenced by thresholded statistical mapping (threshold-free cluster enhancement P _corr > .95). However, this preservation was network-dependent, with no significant (P _corr < .95) changes in the primary visual and sensorimotor networks.

Conclusions: NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity after ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable end point for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation.