TY  - JOUR
A1  - Schuhmann, Michael K.
A1  - Bieber, Michael
A1  - Franke, Maximilian
A1  - Kollikowski, Alexander M.
A1  - Stegner, David
A1  - Heinze, Katrin G.
A1  - Nieswandt, Bernhard
A1  - Pham, Mirko
A1  - Stoll, Guido
T1  - Platelets and lymphocytes drive progressive penumbral tissue loss during middle cerebral artery occlusion in mice
JF  - Journal of Neuroinflammation
N2  - Background

In acute ischemic stroke, cessation of blood flow causes immediate tissue necrosis within the center of the ischemic brain region accompanied by functional failure in the surrounding brain tissue designated the penumbra. The penumbra can be salvaged by timely thrombolysis/thrombectomy, the only available acute stroke treatment to date, but is progressively destroyed by the expansion of infarction. The underlying mechanisms of progressive infarction are not fully understood.

Methods

To address mechanisms, mice underwent filament occlusion of the middle cerebral artery (MCAO) for up to 4 h. Infarct development was compared between mice treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab) or rat immunoglobulin G (IgG) Fab as control treatment. Moreover, Rag1\(^{−/−}\) mice lacking T-cells underwent the same procedures. Infarct volumes as well as the local inflammatory response were determined during vessel occlusion.

Results

We show that blocking of the platelet adhesion receptor, glycoprotein (GP) Ibα in mice, delays cerebral infarct progression already during occlusion and thus before recanalization/reperfusion. This therapeutic effect was accompanied by decreased T-cell infiltration, particularly at the infarct border zone, which during occlusion is supplied by collateral blood flow. Accordingly, mice lacking T-cells were likewise protected from infarct progression under occlusion.

Conclusions

Progressive brain infarction can be delayed by blocking detrimental lymphocyte/platelet responses already during occlusion paving the way for ultra-early treatment strategies in hyper-acute stroke before recanalization.
KW  - ischemic penumbra
KW  - glycoprotein receptor Ib
KW  - T-cells
KW  - ischemic stroke
KW  - thrombo-inflammation
KW  - middle cerebral artery occlusion
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259172
VL  - 18
IS  - 1
ER  - 
TY  - JOUR
A1  - Franke, Maximilian
A1  - Bieber, Michael
A1  - Stoll, Guido
A1  - Schuhmann, Michael Klaus
T1  - Validity and Efficacy of Methods to Define Blood Brain Barrier Integrity in Experimental Ischemic Strokes: A Comparison of Albumin Western Blot, IgG Western Blot and Albumin Immunofluorescence
JF  - Methods and Protocols
N2  - The clinical and preclinical research of ischemic strokes (IS) is becoming increasingly comprehensive, especially with the emerging evidence of complex thrombotic and inflammatory interactions. Within these, the blood brain barrier (BBB) plays an important role in regulating the cellular interactions at the vascular interface and is therefore the object of many IS-related questions. Consequently, valid, economic and responsible methods to define BBB integrity are necessary. Therefore, we compared the three ex-vivo setups albumin Western blot (WB), IgG WB and albumin intensity measurement (AIM) with regard to validity as well as temporal and economic efficacy. While the informative value of the three methods correlated significantly, the efficacy of the IgG WB dominated.
KW  - IgG
KW  - albumin
KW  - immunohistochemistry
KW  - Western blot
KW  - stroke
KW  - tMCAO
KW  - blood brain barrier
KW  - neuroinflammation
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234214
SN  - 2409-9279
VL  - 4
IS  - 1
ER  -