Dataset Information

Delayed Recanalization Promotes Functional Recovery in Rats Following Permanent Middle Cerebral Artery Occlusion.

ABSTRACT: Most large vessel stroke patients have permanent occlusion, for which there are no current treatment options. Recent case studies have indicated delayed recanalization, that is recanalization outside of the 6-h treatment window, may lead to improved outcome. We hypothesized that delayed recanalization will restore cerebral blood flow, leading to improved function in rats. Male SD rats were subjected to pMCAO or sham surgery. Delayed recanalization was performed on either day 3, 7, or 14 after pMCAO in a subset of animals. Cerebral blood flow was monitored during suture insertion, during recanalization, and then at sacrifice. Neurological function was evaluated for 1 week after delayed recanalization and at 4 weeks post-ictus. After sacrifice, cerebral morphology was measured. Compared to no treatment, delayed recanalization restored cerebral blood flow, leading to sensorimotor recovery, improved learning and memory, reduced infarct volume, and increased neural stem/progenitor cells within the infarction. The data indicate that earlier delayed recanalization leads to better functional and histological recovery. Yet, even restoring cerebral blood flow 14 days after pMCAO allows for rats to regain sensorimotor function. This exploratory study suggests that delayed recanalization may be a viable option for treatment of permanent large vessel stroke.

SUBMITTER: McBride DW

PROVIDER: S-EPMC6513323 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Delayed Recanalization Promotes Functional Recovery in Rats Following Permanent Middle Cerebral Artery Occlusion.

McBride Devin William DW Wu Guangyong G Nowrangi Derek D Flores Jerry J JJ Hui Liang L Krafft Paul R PR Zhang John H JH

Translational stroke research 20180121 2

Most large vessel stroke patients have permanent occlusion, for which there are no current treatment options. Recent case studies have indicated delayed recanalization, that is recanalization outside of the 6-h treatment window, may lead to improved outcome. We hypothesized that delayed recanalization will restore cerebral blood flow, leading to improved function in rats. Male SD rats were subjected to pMCAO or sham surgery. Delayed recanalization was performed on either day 3, 7, or 14 after pM ...[more]

PMID: 29354887

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Project description:BackgroundArgon treatment following experimental neurotrauma has been found neuroprotective in an array of in vivo and in vitro models. The inherent cellular and molecular mechanisms are still unknown. We seeked to shed light on these processes by examinig the cellular distribution and the expression of inflammatory markers and growth factors in argon treated brain tissue.MethodsMale adult Sprague-Dawley rats were randomly assigned to one of the study groups: sham surgery + placebo, sham surgery + argon, tMCAO + placebo, and tMCAO + argon. Animals underwent 2 h-transient middle cerebral artery occlusion (tMCAO) using the endoluminal thread model or sham surgery without tMCAO. After the first hour of tMCAO or sham surgery a 1 h inhalative argon (50% argon/50% O2) or placebo (50% N2/50% O2) treatment was performed. Brains were removed and evaluated after 24 h. RealTime-PCR was performed from biopsies of the penumbra and contralateral corresponding regions. Paraffin sections were immunostained with antibodies against GFAP, NeuN, and Iba1. Cell counts of astrocytes, neurons and microglia in different cortical regions were performed in a double-blinded manner.ResultsFifteen animals per tMCAO group and twelve sham + placebo respectively eleven sham + argon animals completed the interventional procedure. We identified several genes (IL-1β, IL-6, iNOS, TGF-β, and NGF) whose transcription was elevated 24 h after the study intervention, and whose expression levels significantly differed between argon treatment and placebo following tMCAO. Except for the core region of ischemia, cell numbers were comparable between different treatment groups.ConclusionIn our study, we found an elevated expression of several inflammatory markers and growth factors following tMCAO + argon compared to tMCAO + placebo. Although conflicting the previously described neuroprotective effects of argon following experimental ischemia, these findings might still be associated with each other. Further studies will have to evaluate their relevance and potential relationship.

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Delayed Recanalization Promotes Functional Recovery in Rats Following Permanent Middle Cerebral Artery Occlusion.

Publications

Delayed Recanalization Promotes Functional Recovery in Rats Following Permanent Middle Cerebral Artery Occlusion.

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