Abstract | BACKGROUND: METHODS: Using the selective A3AR agonist, MRS5980, we evaluated the effects of A3AR activation on the pathological outcomes and cognitive function in CD1 male mouse models of TBI. RESULTS: When measured 24 h after controlled cortical impact (CCI) TBI, male mice treated with intraperitoneal injections of MRS5980 (1 mg/kg) had reduced secondary tissue injury and brain infarction than vehicle-treated mice with TBI. These effects were associated with attenuated neuroinflammation marked by reduced activation of nuclear factor of kappa light polypeptide gene enhancer in B cells (NFκB) and MAPK (p38 and extracellular signal-regulated kinase (ERK)) pathways and downstream NOD-like receptor pyrin domain-containing 3 inflammasome activation. MRS5980 also attenuated TBI-induced CD4+ and CD8+ T cell influx. Moreover, when measured 4-5 weeks after closed head weight-drop TBI, male mice treated with MRS5980 (1 mg/kg) performed significantly better in novel object-placement retention tests (NOPRT) and T maze trials than untreated mice with TBI without altered locomotor activity or increased anxiety. CONCLUSION: Our results provide support for the beneficial effects of small molecule A3AR agonists to mitigate secondary tissue injury and cognitive impairment following TBI.
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Authors | Susan A Farr, Salvatore Cuzzocrea, Emanuela Esposito, Michela Campolo, Michael L Niehoff, Timothy M Doyle, Daniela Salvemini |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 17
Issue 1
Pg. 339
(Nov 12 2020)
ISSN: 1742-2094 [Electronic] England |
PMID | 33183330
(Publication Type: Journal Article)
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Chemical References |
- Adenosine A3 Receptor Agonists
- Receptor, Adenosine A3
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Topics |
- Adenosine A3 Receptor Agonists
(administration & dosage)
- Animals
- Brain Injuries, Traumatic
(drug therapy, metabolism, pathology)
- Drug Delivery Systems
(methods)
- Male
- Mice
- Mice, Inbred C57BL
- Neurocognitive Disorders
(drug therapy, metabolism, pathology)
- Receptor, Adenosine A3
(metabolism)
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