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Deletion of the adenosine A 1 receptor gene does not alter neuronal damage following ischaemia in vivo or in vitro
Author(s) -
Olsson Tomas,
Cronberg Tobias,
Rytter Anna,
Asztély Fredrik,
Fredholm Bertil B.,
Smith MajLis,
Wieloch Tadeusz
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2004.03564.x
Subject(s) - adenosine , neuroprotection , hippocampal formation , knockout mouse , pharmacology , adenosine receptor , ischemia , adenosine a1 receptor , excitatory postsynaptic potential , adenosine a3 receptor , in vivo , biology , neurotransmission , inhibitory postsynaptic potential , gene knockout , receptor , neuroscience , medicine , endocrinology , biochemistry , gene , agonist , genetics
Extracellular adenosine is dramatically increased during cerebral ischaemia and is considered to be neuroprotective due to its inhibitory effect on synaptic transmission mediated by the adenosine A 1 receptor (A 1 R). We investigated the importance of the A 1 R in a mouse model of global ischaemia and in a murine hippocampal slice culture model of in vitro ischaemia, using mice with the A 1 R gene deleted. In brains from mice lacking the A 1 R, damage induced by global ischaemia was similar to that in wild‐type animals. In contrast, treatment with a selective A 1 R antagonist [8‐cyclo‐pentyl theophylline (8‐CPT)], administered before the ischaemic insult in naive wild‐type mice, exacerbated the neuronal damage following global ischaemia. Although the inhibitory action of adenosine on excitatory neurotransmission in hippocampal slices was lost in A 1 R knockout mice, there was no difference in damage between slices from wild‐type and knockout mice after in vitro ischaemia. The results suggest that some effects of the A 1 R are compensated for in knockout animals.