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

Autor: Stacey Sellers, Erica Sequeira, Daniel G. Baden, Dina Akasheh, Marsha L. Pierce, William H. Gerwick, Thomas F. Murray
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Aging
Synaptogenesis
Pharmaceutical Science
Gating
Transgenic
Mice
0302 clinical medicine
Drug Discovery
Excitatory Amino Acid Agonists
Pharmacology
Toxicology and Pharmaceutics (miscellaneous)
Stroke
lcsh:QH301-705.5
Cerebral Cortex
Neuronal Plasticity
Chemistry
Oxocins
Rehabilitation
Pharmacology and Pharmaceutical Sciences
medicine.anatomical_structure
Cerebral cortex
Neurological
NMDA receptor
Physical Chemistry (incl. Structural)
Neurite
Medicinal & Biomolecular Chemistry
neuroplasticity
Mice
Transgenic
Motor Activity
Article
Injections
03 medical and health sciences
Bacterial Proteins
Neuroplasticity
medicine
ischemic stroke
Animals
cardiovascular diseases
Animal
Sodium channel
peri-infarct
Neurosciences
Recovery of Function
medicine.disease
Brain Disorders
Disease Models
Animal
Luminescent Proteins
030104 developmental biology
lcsh:Biology (General)
Disease Models
Marine Toxins
Thrombotic Stroke
Neuroscience
030217 neurology & neurosurgery
brevetoxin
Zdroj: Marine Drugs, Vol 18, Iss 374, p 374 (2020)
Marine drugs, vol 18, iss 7
Marine Drugs
Volume 18
Issue 7
ISSN: 1660-3397
Popis: 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&ndash
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.
Databáze: OpenAIRE
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