Article
Morphological analysis of the perihematomal zone after intrahematomal sonothrombolysis enhanced rtpa-fibrinolysis in a porcine model of intracerebral hemorrhage
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Authors
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Julia Masomi-Bornwasser
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurochirurgie, Mainz, Deutschland
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Axel Heimann
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, neurochirurgisches Institut für Pathophysiologie, Mainz, Deutschland
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Christian Schneider
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurochirurgie, Mainz, Deutschland
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Tristan Klodt
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Neuropathologie, Mainz, Deutschland
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Florian Ringel
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurochirurgie, Mainz, Deutschland
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Naureen Keric
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurochirurgie, Mainz, Deutschland
| Published: | June 18, 2018 |
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Outline
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Objective: Intralesional ultrasound in combination with rtPA showed an accelerated effectiveness of hematoma dissolution in a small clinical trial. Previously we found a significant increase of rtPA-based clot lysis using intralesional ultrasound in a porcine model of intracerebral hemorrhage (ICH). Edema/microbleeding are known as side effects of rtPA-/ultrasoundfibrinolysis. We investigated early morphological changes in the perihematomal zone after rtPA/ ultrasound treatment in a porcine model of ICH
Methods: 21 male pigs underwent right frontal ICH in intubation narcosis. Afterwards they were randomized in 4 treatment groups: group 1 (drainage only; n=3), group 2 (rtPA; n=6), group 3 (ultrasound; n=6), and group 4 (ultrasound+rtPA; n=6). After the different treatments via the intrahematomal catheter a 1 h period of drainage of the liquefied hematoma followed. Animals were euthanized 6 h after ictus, brains were fixed with 4 % PFA and embedded in paraffin. HE staining and immunohistochemistry (micro hemorrhages, edema, GFAP, Iba1, c-FOS) were performed of the rostral and dorsal perihematomal region and compared to the contralateral hemispheres. A semiquantitative evaluation was performed by a blinded investigator (score: 0=no occurrence, 1=slight occurrence; 2=high occurrence).
Results: No differences were observed in the amount of micro hemorrhages between the 4 treatment groups (group 1: 1±0.89, group 2: 0.92±0.51; group 3: 01.08±0.29 and group 4: 1.08±0.52). No micro hemorrhages were present in the contralateral hemispheres. Perihematomal edema did not differ between the 4 treatment groups in the ipsilateral hemispheres (group 1: 1.17±0.75; group 2: 0.92±0.29; group 3: 1±0; group 4: 1±0), but was significantly higher in the contralateral hemispheres in the untreated animals (p<0.0001). Immunohistochemistry revealed no differences in the early immediate neuronal marker c-FOS and microglial marker Iba-1. Interestingly GFAP presence was significantly higher in the contralateral hemispheres in the untreated group compared to the other treatment groups (group 2 p=0.0444; group 3 p=0.0112; group 4 p=0.0025).
Conclusion: No marked changes were observed in the ipsilateral perihematomal region in the early postictal phase. The contralateral hemisphere showed more edema and GFAP expression in the untreated group, which might be attributed to the persistent compressive effect of the large ICH. Side effects like micro hemorrhages and edema could not be attributed to the rtPA or ultrasound treatment.
