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Mouse spinal cord compression injury is reduced by either activation of the adenosine A2A receptor on bone marrow-derived cells or deletion of the A2A receptor on non-bone marrow-derived cells.

Abstract：

:Activation of the adenosine A(2A) receptor (A(2A)R) at the time of reperfusion has been shown to reduce ischemia-reperfusion injury in peripheral tissues and spinal cord. In this study we show that treating mice with the A(2A)R agonist, 4-{3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid methyl ester for four days beginning before or just after the onset of reperfusion after compression-induced spinal cord injury rapidly (within 1 day) and persistently (>42 days) reduces locomotor dysfunction and spinal cord demyelination. Protection is abolished in knockout/wild type bone marrow chimera mice selectively lacking the A(2A)R only on bone marrow-derived cells but retaining receptors on other tissues including blood vessels. Paradoxically, reduced spinal cord injury is also noted in A(2A)R -/- mice, and in wild type/knockout bone marrow chimera mice selectively lacking the A(2A)R on non-bone marrow-derived cells, or in mice treated with the A(2A) antagonist, 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol. The greatest protection is seen in knockout/wild type bone marrow chimera mice treated with 4-{3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid methyl ester, i.e. by activating the A(2A)R in mice expressing the receptor only in bone marrow-derived cells. The data suggest that inflammatory bone marrow-derived cells are the primary targets of A(2A) agonist-mediated protection. We conclude that A(2A) agonists or other interventions that inhibit inflammation during and after spinal cord ischemia may be effective in reducing spinal cord injury in patients, but excessive or prolonged stimulation of the A(2A)R may be counterproductive. It may be possible to devise strategies to produce optimal spinal cord protection by exploiting temporal differences in A(2A)R-mediated responses.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Li Y,Oskouian RJ,Day YJ,Rieger JM,Liu L,Kern JA,Linden J

doi

10.1016/j.neuroscience.2006.05.014

subject

Has Abstract

pub_date

2006-09-15 00:00:00

pages

2029-39

issue

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(06)00666-X

journal_volume

141

pub_type

杂志文章

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Mouse spinal cord compression injury is reduced by either activation of the adenosine A2A receptor on bone marrow-derived cells or deletion of the A2A receptor on non-bone marrow-derived cells.