TY  - JOUR
A1  - Gelhard, Sarah
A1  - Kestner, Roxane-Isabelle
A1  - Armbrust, Moritz
A1  - Steinmetz, Helmuth
A1  - Förch, Christian
A1  - Bohmann, Ferdinand
T1  - Exploring contraindications for thrombolysis: risk of hemorrhagic transformation and neurological deterioration after thrombolysis in mice with recent ischemic stroke and hyperglycemia
T2  - Journal of Clinical Medicine
N2  - (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.
KW  - stroke
KW  - thrombolysis
KW  - hemorrhagic transformation
KW  - hyperglycemia
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72039
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-720399
SN  - 2077-0383
N1  - This study was supported in part by a grant from the Goethe University Hospital Frankfurt (Nachwuchsforscher).
VL  - 11
IS  - 12, art. 3343
SP  - 1
EP  - 13
PB  - MDPI
CY  - Basel
ER  -