Neuroprotective Roles of the Adenosine A₃ Receptor Agonist AST-004 in Mouse Model of Traumatic Brain Injury.

ABSTRACT: Traumatic brain injury (TBI) remains one of the greatest public health concerns with increasing morbidity and mortality rates worldwide. Our group reported that stimulation of astrocyte mitochondrial metabolism by P2Y₁ receptor agonists significantly reduced cerebral edema and reactive gliosis in a TBI model. Subsequent data on the pharmacokinetics (PK) and rapid metabolism of these compounds suggested that neuroprotection was likely mediated by a metabolite, AST-004, which binding data indicated was an adenosine A₃ receptor (A₃R) agonist. The neuroprotective efficacy of AST-004 was tested in a control closed cortical injury (CCCI) model of TBI in mice. Twenty-four (24) hours post-injury, mice subjected to CCCI and treated with AST-004 (0.22 mg/kg, injected

SUBMITTER: Bozdemir E 

PROVIDER: S-EPMC8804149 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature