Effects of intracarotid arterial injection of cyclosporin A and spontaneous hypothermia on brain damage incurred after a long period of global ischemia

A recent study showed that a single intracarotid arterial injection of cycl osporin A (CsA) can dramatically reduce infarct volume in rats subjected to transient focal ischemia. The present experiments were undertaken to inves tigate whether intracarotid arterial injection of CsA reduces brain damage after global ischemia. Since hypothermia is also an efficacious factor in p reventing ischemic brain damage, in the second part of the experiments we t ested whether a combination of hypothermia and CsA would provide additional brain protection. Global ischemia of a 30-min duration was induced in the rat. CsA (10 mg/kg) was injected into the carotid artery immediately after reperfusion. Hypothermia was instituted after ischemia by allowing spontane ous head temperature to fall to 30-32 degreesC, while body temperature was upheld at 37 degreesC. The results demonstrated that vehicle-treated animal s could not survive beyond 1-2 days after reperfusion, and the histopatholo gical outcome in a separate group of rats perfusion-fixed after 1 day reper fusion showed 80-100% brain damage in the caudoputamen, and in the hippocam pal CA1, CA3, CA4 and dentate gyrus subregions. Microinfarction and grade 3 damage were frequently observed in the cingulate and parietal cortex and i n the thalamus. CsA moderately prolonged animal survival to 3 days after re perfusion and reduced brain damage to grade 2 in the cortical areas and the thalamus. Hypothermia further increased animal survival to at least 6 days after reperfusion and reduced brain damage to 30% in the caudoputamen, to close to zero in the CA3, CA4, and dentate gyrus, and to grade 1-2 in the c ortical areas and the thalamus. The combination of hypothermia and CsA did not give additional protection. (C) 2001 Elsevier Science B.V. All rights r eserved.