TY - JOUR
T1 - Monitoring stroke progression: In vivo imaging of cortical perfusion, blood-brain barrier permeability and cellular damage in the rat photothrombosis model
AU - Schoknecht, Karl
AU - Prager, Ofer
AU - Vazana, Udi
AU - Kamintsky, Lyn
AU - Harhausen, Denise
AU - Zille, Marietta
AU - Figge, Lena
AU - Chassidim, Yoash
AU - Schellenberger, Eyk
AU - Kovács, Richard
AU - Heinemann, Uwe
AU - Friedman, Alon
N1 - Publisher Copyright:
© 2014 ISCBFM All rights reserve.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex.
AB - Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex.
UR - http://www.scopus.com/inward/record.url?scp=84922248440&partnerID=8YFLogxK
U2 - 10.1038/jcbfm.2014.147
DO - 10.1038/jcbfm.2014.147
M3 - Journal articles
C2 - 25160672
AN - SCOPUS:84922248440
SN - 0271-678X
VL - 34
SP - 1791
EP - 1801
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 11
ER -
