(1) Intravenous thrombolysis with recombinant
tissue plasminogen activator (rt-PA) in patients with
acute ischemic stroke is limited because of several
contraindications. In routine clinical practice, patients with a recent
stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery
embolism and
myocardial infarction with a recent
stroke. In this translational study, we evaluated whether rt-PA treatment after experimental
ischemic stroke with or without additional
hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old
infarct area. (2) In total, 72 male C57BL/6N mice were used.
Ischemic stroke (index
stroke) was induced by transient
middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index
stroke to determine whether a recent
ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop
hyperglycemia were pre-treated with
streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, p = 0.02; at 14 days, p = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (p = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial
hemorrhages could be detected. (4) Thrombolysis after recent
ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However,
hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role.