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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 Pcorr > .95). However, this preservation was network-dependent, with no significant (Pcorr < .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.
ABBREVIATIONS:
- FWE
- family-wise error
- ICA
- independent component analysis
- MCAO
- middle cerebral artery occlusion
- NEH
- norepinephrine and hydralazine
- rs-fMRI
- resting-state fMRI
- RSN
- resting-state network
- TFCE
- threshold-free cluster enhancement
- © 2024 by American Journal of Neuroradiology