Spreading Depolarizations Suppress Hematoma Growth in Hyperacute Intracerebral Hemorrhage in Mice.

Autor:	Fischer P; Neurovascular Research Unit, Department of Radiology (P.F., I.T., K.S., A.M., T.I., T.T., T.Q., D.Y.C., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown.; Klinik und Hochschulambulanz für Neurologie, NeuroCure Excellence Cluster and Center for Stroke Research (P.F., I.T., M.E.), Charité Universitätsmedizin Berlin, Germany., Tamim I; Neurovascular Research Unit, Department of Radiology (P.F., I.T., K.S., A.M., T.I., T.T., T.Q., D.Y.C., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown.; Klinik und Hochschulambulanz für Neurologie, NeuroCure Excellence Cluster and Center for Stroke Research (P.F., I.T., M.E.), Charité Universitätsmedizin Berlin, Germany., Sugimoto K; Neurovascular Research Unit, Department of Radiology (P.F., I.T., K.S., A.M., T.I., T.T., T.Q., D.Y.C., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown., Morais A; Neurovascular Research Unit, Department of Radiology (P.F., I.T., K.S., A.M., T.I., T.T., T.Q., D.Y.C., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown., Imai T; Neurovascular Research Unit, Department of Radiology (P.F., I.T., K.S., A.M., T.I., T.T., T.Q., D.Y.C., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown., Takizawa T; Neurovascular Research Unit, Department of Radiology (P.F., I.T., K.S., A.M., T.I., T.T., T.Q., D.Y.C., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown.; Department of Neurology, Keio University School of Medicine, Tokyo, Japan (T.T.)., Qin T; Neurovascular Research Unit, Department of Radiology (P.F., I.T., K.S., A.M., T.I., T.T., T.Q., D.Y.C., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown., Schlunk F; Department of Neuroradiology (F.S.), Charité Universitätsmedizin Berlin, Germany., Endres M; Klinik und Hochschulambulanz für Neurologie, NeuroCure Excellence Cluster and Center for Stroke Research (P.F., I.T., M.E.), Charité Universitätsmedizin Berlin, Germany.; German Center for Neurodegenerative Diseases, Partner Site Berlin, Germany (M.E.).; German Centre for Cardiovascular Research, Partner Site Berlin, Germany (M.E.)., Yaseen MA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (M.A.Y., S.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown.; Now with Department of Bioengineering, Northeastern University, Boston, MA (M.A.Y.)., Chung DY; Neurovascular Research Unit, Department of Radiology (P.F., I.T., K.S., A.M., T.I., T.T., T.Q., D.Y.C., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown.; Department of Neurology (D.Y.C., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown., Sakadzic S; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (M.A.Y., S.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown., Ayata C; Neurovascular Research Unit, Department of Radiology (P.F., I.T., K.S., A.M., T.I., T.T., T.Q., D.Y.C., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown.; Department of Neurology (D.Y.C., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown.
Jazyk:	angličtina
Zdroj:	Stroke [Stroke] 2023 Oct; Vol. 54 (10), pp. 2640-2651. Date of Electronic Publication: 2023 Aug 23.
DOI:	10.1161/STROKEAHA.123.042632
Abstrakt:	Background: Spreading depolarizations (SDs) occur in all types of brain injury and may be associated with detrimental effects in ischemic stroke and subarachnoid hemorrhage. While rapid hematoma growth during intracerebral hemorrhage triggers SDs, their role in intracerebral hemorrhage is unknown. Methods: We used intrinsic optical signal and laser speckle imaging, combined with electrocorticography, to investigate the effects of SD on hematoma growth during the hyperacute phase (0-4 hours) after intracortical collagenase injection in mice. Hematoma expansion, SDs, and cerebral blood flow were simultaneously monitored under normotensive and hypertensive conditions. Results: Spontaneous SDs erupted from the vicinity of the hematoma during rapid hematoma growth. We found that hematoma growth slowed down by >60% immediately after an SD. This effect was even stronger in hypertensive animals with faster hematoma growth. To establish causation, we exogenously induced SDs (every 30 minutes) at a remote site by topical potassium chloride application and found reduced hematoma growth rate and final hemorrhage volume (18.2±5.8 versus 10.7±4.1 mm 3 ). Analysis of cerebral blood flow using laser speckle flowmetry revealed that suppression of hematoma growth by spontaneous or induced SDs coincided and correlated with the characteristic oligemia in the wake of SD, implicating the vasoconstrictive effect of SD as one potential mechanism of action. Conclusions: Our findings reveal that SDs limit hematoma growth during the early hours of intracerebral hemorrhage and decrease final hematoma volume. Competing Interests: Disclosures Dr Endres reports grants from Bayer and fees paid to the Charité from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Amgen, Glaxo Smith Kline, Sanofi, Covidien, Novartis, and Pfizer, all outside the submitted work. Dr Ayata reports compensation from Neurelis, Inc, and grants from Takeda Pharmaceutical Company and Praxis, all outside the submitted work. The other authors report no conflicts.
Databáze:	MEDLINE
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