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[Activation of the adenosine A2A receptor at the acute stage of moderate traumatic brain injury enhances the neuroprotective effects of oxaloacetate].
- Source :
-
Sheng li xue bao : [Acta physiologica Sinica] [Sheng Li Xue Bao] 2022 Aug 25; Vol. 74 (4), pp. 505-512. - Publication Year :
- 2022
-
Abstract
- The purpose of the present study was to investigate the effect of glutamate scavenger oxaloacetate (OA) combined with CGS21680, an adenosine A2A receptor (A2AR) agonist, on acute traumatic brain injury (TBI), and to elucidate the underlying mechanisms. C57BL/6J mice were subjected to moderate-level TBI by controlled cortical impact, and then were treated with OA, CGS21680, or OA combined with CGS21680 at acute stage of TBI. At 24 h post TBI, neurological severity score, brain water content, glutamate concentration in cerebrospinal fluid (CSF), mRNA and protein levels of IL-1β and TNF-α, mRNA level and activity of glutamate oxaloacetate aminotransferase (GOT), and ATP level of brain tissue were detected. The results showed that neurological deficit, brain water content, glutamate concentration in CSF, and the inflammatory cytokine IL-1β and TNF-α production were exacerbated in CGS21680 treated mice. Administrating OA suppressed the rise of both glutamate concentration in CSF and brain water content, and elevated the ATP level of cerebral tissue. More interestingly, neurological deficit, brain edema, glutamate concentration, IL-1β and TNF-α levels were ameliorated significantly in mice treated with OA combined with CGS21680. The combined treatment exhibited better therapeutic effects than single OA treatment. We also observed that GOT activity was enhanced in single CGS21680 treatment group, and both the GOT mRNA level and GOT activity were up-regulated in early-stage combined treatment group. These results suggest that A2AR can improve the efficiency of GOT and potentiate the ability of OA to metabolize glutamate. This may be the mechanism that A2AR activation in combination group augmented the neuroprotective effect of OA rather than aggravated the brain damages. Taken together, the present study provides a new insight for the clinical treatment of TBI with A2AR agonists and OA.
- Subjects :
- Adenosine Triphosphate
Animals
Brain Injuries drug therapy
Brain Injuries genetics
Brain Injuries metabolism
Glutamic Acid
Mice
Mice, Inbred C57BL
RNA, Messenger
Tumor Necrosis Factor-alpha genetics
Water
Adenosine A2 Receptor Agonists pharmacology
Adenosine A2 Receptor Agonists therapeutic use
Brain Injuries, Traumatic drug therapy
Brain Injuries, Traumatic genetics
Brain Injuries, Traumatic metabolism
Neuroprotective Agents pharmacology
Neuroprotective Agents therapeutic use
Oxaloacetic Acid pharmacology
Oxaloacetic Acid therapeutic use
Receptor, Adenosine A2A genetics
Receptor, Adenosine A2A metabolism
Subjects
Details
- Language :
- Chinese
- ISSN :
- 0371-0874
- Volume :
- 74
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Sheng li xue bao : [Acta physiologica Sinica]
- Publication Type :
- Academic Journal
- Accession number :
- 35993201