Neuroprotective effect of aspirin by inhibition of glutamate release after permanent focal cerebral ischaemia in rats.
Aspirin reduces the size of infarcts after ischaemic stroke. Although this fact has been attributed to its anti-platelet actions, direct neuroprotective effects have also been reported. We have recently demonstrated that aspirin is neuroprotective by inhibiting glutamate release in 'in vitro' models of brain ischaemia, via an increase in ATP production. The present study was designed to determine whether the inhibition of glutamate release induced by aspirin might be protective in a whole-animal model of permanent focal brain ischaemia. Focal brain ischaemia was produced in male adult Fischer rats by occluding both the common carotid and middle cerebral arteries. Central and serum glutamate levels were determined at fixed intervals after occlusion. The animals were then killed and infarct volume was measured. Aspirin (30 mg/kg i.p. administered 2 h before the occlusion) produced a significant reduction in infarct volume, an effect that correlated with the inhibition caused by aspirin on ischaemia-induced increase in brain and serum glutamate concentrations after the onset of the ischaemia. Aspirin also inhibited ischaemia-induced decrease in brain ATP levels. Our present findings show a novel mechanism for the neuroprotective effects of aspirin, which takes place at concentrations in the anti-aggregant-analgesic range, useful in the management of patients with risk of ischaemic events.
De Cristóbal
J
J
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid (UCM), Madrid, Spain.
Moro
M A
MA
Dávalos
A
A
Castillo
J
J
Leza
J C
JC
Camarero
J
J
Colado
M I
MI
Lorenzo
P
P
Lizasoain
I
I
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002544:Cerebral Infarction / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid / Q000097:blood / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009994:Osmolar Concentration; D051381:Rats; D011916:Rats, Inbred F344
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D001241:Aspirin