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Brevetoxin Induced Dendritic Arborization and Functional Recovery in a Murine Post‐Stroke Model
Author(s) -
Sequeira Erica,
Pierce Marsha,
Gomez Dina,
Murray Thomas
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.815.15
Subject(s) - glutamatergic , neuroscience , excitatory postsynaptic potential , neuroplasticity , dendritic spine , nmda receptor , synaptic plasticity , chemistry , stroke (engine) , medicine , biology , glutamate receptor , receptor , hippocampal formation , biochemistry , mechanical engineering , engineering , inhibitory postsynaptic potential
RATIONALE Stroke is a leading cause of long term disability rendering most survivors incapable of walking without assistance. This condition triggers structural and physiological changes in neuronal circuits adjacent to the infarct region, termed peri‐infarct area, that plays a key role in recovery and represents a potential therapeutic target. Pyramidal neurons are abundant in the cerebral cortex and form excitatory glutamatergic synaptic contacts. These glutamatergic neuron dendritic domains play a role in excitability and neuronal plasticity. Synaptic plasticity is largely mediated through N‐methyl D‐aspartate receptors (NMDARs) and calcium [[Ca 2+ ]] dependent signaling pathways. Intracellular sodium [[Na + ] i ] acts as a signaling molecule in as much as it exerts and regulates NMDAR channel activity. Brevetoxin‐2 (PbTx‐2) is a voltage‐gated sodium channel (VGSC) gating modifier that increases [Na + ] i , upregulates NMDAR function and increases downstream Ca 2+ dependent signaling pathways. OBJECTIVE Purpose of this study was to develop a sensitive and a reproducible behavioral test to evaluate motor movements post‐stroke in mice and to test the effect of PbTx‐2 on recovery of movement. In addition, this study aimed to examine the effect of PbTx‐2 on dendritic arbor complexity of cerebral cortical layer V pyramidal cells. METHODS A stroke was produced by administration of an intraperitoneal injection of Rose Bengal dye followed by a 12.5 min light illumination of the caudal forelimb area of the motor cortex region. Hydrogel surgery was then performed on Day 5 post stroke which involves drilling the skull to inject Hydrogel vehicle or Hydrogel + 100 pmol PbTx‐2 using a Hamilton syringe. A Pasta Matrix Reach Task was used to determine the number of pieces of pasta retrieved post‐stroke and post‐Hydrogel treatment from a 5×5 matrix of pasta. Brain slices were imaged using Leica TCS SP8 MP confocal microscope that produces 3D images which were then analyzed with Imaris 8.3 software to measure dendritic arbor complexity by Sholl analysis. RESULTS The results demonstrated that the number of pastas retrieved was significantly impaired on Day 1 post‐stroke with a subsequent improvement following treatment with 100 pmol PbTx‐2 as compared to the control mice. In addition, PbTx‐2 treated layer V pyramidal neurons also had a greater dendritic arbor complexity in comparison to controls. CONCLUSION Preclinical research in a murine stroke model provided a behavioral assessment of neural insult‐induced functional deficits and PbTx‐2 induced motor recovery. The Pasta Matrix Reach Task proved to be a sensitive behavioral measurement for the study of neural impairment and recovery. Increased dendritic arbor complexity in layer V pyramidal cells indicates that PbTx‐2 can potentially aid neuroplasticity at the peri‐infarct region. Support or Funding Information NIH R01NS053398