Ischemic preconditioning as induction of ischemic tolerance after transient ischemic attacks in human brain: its clinical relevance

Ischemic preconditioning has been well-established in different animal models of cerebral ischemia. Suggesting that transient ischemic attack (TIAs) may represent a clinical model of ischemic tolerance, patients with ipsilateral TIA before ischemic stroke may have a better neurological outcome compared to patients without TIA before ischemic stroke. A retrospective case-control study. Analysis of clinical and neuroradiological findings of 130 patients treated with local intra-arterial thrombolysis using urokinase after ischemic stroke between January 2000 and May 2002. Eleven patients (8%) demonstrated prestroke ipsilateral TIA in the same vascular territory. Despite no significant differences in baseline characteristics, independence (modified Ranking Scale score) and neurological outcome (NIHS score) were significantly associated with prior TIA in multivariante models. Patients with prestroke TIA, showing a similar clinical picture (NIHS score) on admission, demonstrated a more favorable outcome (NIHS score (p < 0.001) and modified Ranking score (p < 0.0001)) compared to patients with unheralded ischemic stroke. The interval between TIA and ischemic stroke (1-7 days), duration of TIAs (0-20 min) and number of TIAs (2-3) influenced the better outcome in this patients' subgroup. In addition, we could show an induction of ischemic tolerance by prestroke ASA treatment in patients without previous new-onset TIA. Two to three ipsilateral TIA of the same vascular territory and of up to 20 min duration within 1-7 days may lead to ischemic tolerance to a subsequent ischemic stroke as demonstrated by significantly diminished infarct extention throughout all cortical imagines in neuroradiological studies. The role of ASA has to been further elucidated.