Journal article
Emergent Uric Acid Treatment is Synergistic with Mechanical Recanalization in Improving Stroke Outcomes in Male and Female Rats
Neuroscience, Vol.388, pp.263-273
09/15/2018
DOI: 10.1016/j.neuroscience.2018.07.045
PMID: 30077000
Abstract
[Display omitted]
•The effects of uric acid in an ischemic stroke model relevant to mechanical thrombectomy treatment were assessed.•At 24 h after stroke, neurofunctional impairment and infarct were reduced in male and female rats by uric acid treatment.•Beneficial effects of uric acid were better manifested in brain cortex after postischemic hyperperfusion.•After a 7-day follow-up, male rats subjected to uric acid treatment still showed improved outcomes.•Additional clinical testing of uric acid as an adjunctive treatment to mechanical thrombectomy is warranted.
Preclinical and clinical studies support a promising, albeit not definitive, neuroprotective effect of emergent uric acid (UA) administration in ischemic stroke. We assessed the effects of UA in an ischemic stroke model relevant to the current treatment paradigm of mechanical thrombectomy within the STAIR/RIGOR recommendations. A cohort of male and female Wistar rats was subjected to ischemic stroke with mechanical recanalization under physiological monitoring. The effects of transient middle cerebral artery occlusion (tMCAO) with adjunctive UA (IV, 16 mg/kg) or vehicle treatment were assessed at 24 h and 7 days. Outcomes included neurofunctional impairment, brain infarct (TTC staining, MRI imaging and cresyl violet staining) and edema. At 24 h after tMCAO, neurofunctional scores and brain infarct were significantly reduced in rats subjected to UA treatment compared to vehicle, with a selective effect of UA on cortical infarct. No differential effect of UA between male and female rats was evidenced, as no significant interaction of sex with stroke outcomes was found. Rats achieving higher reperfusion levels after tMCAO showed superior reduction of neurofunctional impairment, cortical infarct and edema by UA. After a 7-day follow-up, male rats subjected to UA treatment still showed reductions in neurofunctional impairment and infarct size, compared to vehicle treatment. In conclusion, UA treatment immediately after transient ischemia results in a sex-independent, maintained reduction of brain damage and neurological impairment, better manifested in hyperperfusion conditions. This synergistic effect of UA with mechanical recanalization supports additional clinical testing of UA as an adjunctive treatment to mechanical thrombectomy.
Details
- Title: Subtitle
- Emergent Uric Acid Treatment is Synergistic with Mechanical Recanalization in Improving Stroke Outcomes in Male and Female Rats
- Creators
- Alicia Aliena-Valero - Unidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe – Universidad de Valencia, Valencia, SpainMikahela A López-Morales - Unidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe – Universidad de Valencia, Valencia, SpainMaría C Burguete - Unidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe – Universidad de Valencia, Valencia, SpainMaría Castelló-Ruiz - Unidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe – Universidad de Valencia, Valencia, SpainTeresa Jover-Mengual - Unidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe – Universidad de Valencia, Valencia, SpainDavid Hervás - Unidad de Bioestadística, Instituto de Investigación Sanitaria La Fe, Valencia, SpainGermán Torregrosa - Unidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe – Universidad de Valencia, Valencia, SpainEnrique C Leira - Departments of Neurology and Epidemiology, Carver College of Medicine and College of Public Health, University of Iowa, Iowa City, USAÁngel Chamorro - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, SpainJuan B Salom - Unidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe – Universidad de Valencia, Valencia, Spain
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.388, pp.263-273
- DOI
- 10.1016/j.neuroscience.2018.07.045
- PMID
- 30077000
- NLM abbreviation
- Neuroscience
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/501100004587, name: Instituto de Salud Carlos III, award: RD16/0019/0008, RD16/0019/0014; DOI: 10.13039/501100008530, name: European Regional Development Fund; DOI: 10.13039/100008893, name: University of Iowa
- Language
- English
- Date published
- 09/15/2018
- Academic Unit
- Neurology; Epidemiology; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984070598202771
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