Thrombolysis in Experimental Cerebral Amyloid Angiopathy and the Risk of Secondary Intracerebral Hemorrhage

Abstract

Background and Purpose-Intracerebral hemorrhage (ICH) is the most adverse event of thrombolysis in ischemic stroke.Cerebral amyloid angiopathy increases the risk for spontaneous lobar ICH. Although thrombolysis may be performed in cerebral amyloid angiopathy-affected patients, there is still little knowledge available on the risk for secondary ICH. Methods-We investigated the effect of recombinant tissue-type plasminogen activator on experimental ischemic stroke in APP23 transgenic mice (n=18) and wild-type littermates (n=15). Focal ischemic stroke was induced in 26-month-old mice by temporal middle cerebral artery occlusion (filament model), followed by treatment with 10 mg/kg recombinant tissue-type plasminogen activator. Twenty-four hours later, a functional score was assessed and the mice were euthanized for histological analysis. ICH was classified as grades 1 to 3 depending on severity. Results-The groups did not differ regarding mortality (P=0.67) and functional deficit (P=0.18). Compared with wild-type mice, the APP23 genotype was associated with a higher appearance for ICH in the infarct area (P=0.05). ICH severity grades 2 and 3 correlated significantly with infarct size (P=0.004 and 0.008, respectively). Conclusions-The APP23 genotype was not associated with increased mortality or worse functional outcome. Our results suggest an increased risk for ICH in the cerebral amyloid angiopathy-affected brain; however, no ICH was observed outside the ischemic area. (Stroke. 2014;45:2411-2416.)

Management of acute ischaemic stroke in patients with dementia

“…In a meta‐analysis of patients with IS treated with thrombolysis, 9% of patients with CMBs experienced a symptomatic ICH after thrombolysis compared to 4% without CMBs . Two studies examined the effect of tPA in aged APP23 transgenic mouse models of CAA and found a higher risk of ICH in the CAA‐affected brains . One of these studies also examined mortality and functional outcomes and found no differences in APP23 mice compared to control animals .…”

“…Two studies examined the effect of tPA in aged APP23 transgenic mouse models of CAA and found a higher risk of ICH in the CAA‐affected brains . One of these studies also examined mortality and functional outcomes and found no differences in APP23 mice compared to control animals .…”

“…One of these studies also examined mortality and functional outcomes and found no differences in APP23 mice compared to control animals [68].…”

Tissue kallikrein protects against ischemic stroke by suppressing TLR4/NF-κB and activating Nrf2 signaling pathway in rats

“…However, it benefits only a small proportion of patients due to the limited thrombolysis window and the adverse reactions of thrombolytics (2,3). In addition, recanalization may cause severe cerebral ischemia-reperfusion (I/R) injury in the local region (4,5). Accumulating evidence has suggested that inflammatory and oxidative damage serves an important role in cerebral I/R injury (6)(7)(8).…”

Investigating potentially salvageable penumbra tissue in an in vivo model of transient ischemic stroke using sodium, diffusion, and perfusion magnetic resonance imaging

“…Postmortem, 10 µm coronal cryosections were cut at 400 µm intervals and stained with hematoxylin–eosin–saffron (H&E) staining accordingly to previous protocols [19]. …”