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Article

Epicortical Brevetoxin Treatment Promotes Neural Repair and Functional Recovery after Ischemic Stroke

1
Department of Pharmacology and Neuroscience, Creighton University, Omaha, NE 68123, USA
2
Center for Marine Biotechnology & Biomedicine, Scripps Institution of Oceanography, San Diego, La Jolla, CA 92093, USA
3
Center for Marine Science University of North Carolina Wilmington, Wilmington, NC 28409, USA
*
Author to whom correspondence should be addressed.
Mar. Drugs 2020, 18(7), 374; https://doi.org/10.3390/md18070374
Received: 25 June 2020 / Revised: 17 July 2020 / Accepted: 17 July 2020 / Published: 21 July 2020
(This article belongs to the Special Issue Marine Natural Products against Brain Diseases and Injuries)
Emerging literature suggests that after a stroke, the peri-infarct region exhibits dynamic changes in excitability. In rodent stroke models, treatments that enhance excitability in the peri-infarct cerebral cortex promote motor recovery. This increase in cortical excitability and plasticity is opposed by increases in tonic GABAergic inhibition in the peri-infarct zone beginning three days after a stroke in a mouse model. Maintenance of a favorable excitatory–inhibitory balance promoting cerebrocortical excitability could potentially improve recovery. Brevetoxin-2 (PbTx-2) is a voltage-gated sodium channel (VGSC) gating modifier that increases intracellular sodium ([Na+]i), upregulates N-methyl-D-aspartate receptor (NMDAR) channel activity and engages downstream calcium (Ca2+) signaling pathways. In immature cerebrocortical neurons, PbTx-2 promoted neuronal structural plasticity by increasing neurite outgrowth, dendritogenesis and synaptogenesis. We hypothesized that PbTx-2 may promote excitability and structural remodeling in the peri-infarct region, leading to improved functional outcomes following a stroke. We tested this hypothesis using epicortical application of PbTx-2 after a photothrombotic stroke in mice. We show that PbTx-2 enhanced the dendritic arborization and synapse density of cortical layer V pyramidal neurons in the peri-infarct cortex. PbTx-2 also produced a robust improvement of motor recovery. These results suggest a novel pharmacologic approach to mimic activity-dependent recovery from stroke. View Full-Text
Keywords: brevetoxin; ischemic stroke; peri-infarct; neuroplasticity brevetoxin; ischemic stroke; peri-infarct; neuroplasticity
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MDPI and ACS Style

Sequeira, E.; Pierce, M.L.; Akasheh, D.; Sellers, S.; Gerwick, W.H.; Baden, D.G.; Murray, T.F. Epicortical Brevetoxin Treatment Promotes Neural Repair and Functional Recovery after Ischemic Stroke. Mar. Drugs 2020, 18, 374. https://doi.org/10.3390/md18070374

AMA Style

Sequeira E, Pierce ML, Akasheh D, Sellers S, Gerwick WH, Baden DG, Murray TF. Epicortical Brevetoxin Treatment Promotes Neural Repair and Functional Recovery after Ischemic Stroke. Marine Drugs. 2020; 18(7):374. https://doi.org/10.3390/md18070374

Chicago/Turabian Style

Sequeira, Erica, Marsha L. Pierce, Dina Akasheh, Stacey Sellers, William H. Gerwick, Daniel G. Baden, and Thomas F. Murray 2020. "Epicortical Brevetoxin Treatment Promotes Neural Repair and Functional Recovery after Ischemic Stroke" Marine Drugs 18, no. 7: 374. https://doi.org/10.3390/md18070374

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