Neuroprotection with NBQX and thrombolysis with rt-PA in rat embolic stroke

Abstract

The efficacy of delayed thrombolysis with recombinant tissue plasminogen activator was tested in combination with the ischaemic protecting drug NBQX in an embolic stroke model. In 113 rats the carotid territory was embolized with a fibrin-rich clot formed in polyethylene tube. Hemispheric cerebral blood flow (CBF) was measured by intra-arterial 133Xenon injection method before and after embolization. Two hours after embolization 67 animals were treated with tissue plasminogen activator 20 mg kg-1, 46 control animals with saline. NBQX was given to 53 animals, of which 41 animals also received thrombolytic therapy and 12 were saline controls. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after two days, evaluated neuropathologically, and infarct volume was measured. Embolization caused a 60-78% reduction of median CBF. The comparison of post-treatment angiography of thrombolytic treated animals to controls showed significant (p < 0.01) reperfusion in thrombolytic treated animals, while NBQX alone did not enhance reperfusion. Thrombolytic therapy significantly reduced the total infarct volume from 19.5% to 4.5% of embolized hemisphere volume (p = 0.006). NBQX alone reduced total infarct volume from 19.5% to 6.5% and cortical infarct volume from 7.9% to 0.3% (p = 0.03). In thrombolytic treated animals NBQX reduced total infarct volume from 4.5% to 2.1%. The more than 50% reduction of total infarction volume caused by NBQX was not statistically significant due to the variation of infarct size in this model. Small haemorrhagic lesions in infarcts were observed in thrombolytic treated animals. The clinical outcome correlated well with infarct volume.(ABSTRACT TRUNCATED AT 250 WORDS)