Blood-Brain Barrier Alterations Provide Evidence of Subacute Diaschisis in an Ischemic Stroke Rat Model

被引:57
作者
Garbuzova-Davis, Svitlana [1 ,2 ,3 ,4 ]
Rodrigues, Maria C. O. [5 ]
Hernandez-Ontiveros, Diana G. [1 ]
Tajiri, Naoki [1 ]
Frisina-Deyo, Aric [1 ]
Boffeli, Sean M. [1 ]
Abraham, Jerry V. [1 ]
Pabon, Mibel [1 ]
Wagner, Andrew [1 ]
Ishikawa, Hiroto [1 ]
Shinozuka, Kazutaka [1 ]
Haller, Edward [7 ]
Sanberg, Paul R. [1 ,2 ,4 ,6 ]
Kaneko, Yuji [1 ,2 ]
Borlongan, Cesario V. [1 ,2 ]
机构
[1] Univ S Florida, Morsani Coll Med, Ctr Excellence Aging & Brain Repair, Tampa, FL 33620 USA
[2] Univ S Florida, Morsani Coll Med, Dept Neurosurg & Brain Repair, Tampa, FL USA
[3] Univ S Florida, Morsani Coll Med, Dept Mol Pharmacol & Physiol, Tampa, FL USA
[4] Univ S Florida, Morsani Coll Med, Dept Pathol & Cell Biol, Tampa, FL USA
[5] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Internal Med, Sao Paulo, Brazil
[6] Univ S Florida, Morsani Coll Med, Dept Psychiat, Tampa, FL USA
[7] Univ S Florida, Dept Integrat Biol, Tampa, FL USA
基金
美国国家卫生研究院;
关键词
CEREBRAL-ARTERY OCCLUSION; CROSSED CEREBELLAR DIASCHISIS; TRANSHEMISPHERIC DIASCHISIS; HEMORRHAGIC TRANSFORMATION; RISK-FACTORS; PERMEABILITY; AUTOPHAGY; INFLAMMATION; REPERFUSION; MECHANISMS;
D O I
10.1371/journal.pone.0063553
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas. Methodology/Principal Findings: In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO), significant BBB alterations characterized by large Evans Blue (EB) parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices. Conclusions/Significance: These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke.
引用
收藏
页数:15
相关论文
共 77 条
[1]   Inflammatory mediators and modulation of blood-brain barrier permeability [J].
Abbott, NJ .
CELLULAR AND MOLECULAR NEUROBIOLOGY, 2000, 20 (02) :131-147
[2]   Post-ischemic leakiness of the blood-brain barrier: A quantitative and systematic assessment by Patlak plots [J].
Abo-Ramadan, Usama ;
Durukan, Aysan ;
Pitkonen, Miia ;
Marinkovic, Ivan ;
Tatlisumak, Ertugrul ;
Pedrono, Eric ;
Soinne, Lauri ;
Strbian, Daniel ;
Tatlisumak, Turgut .
EXPERIMENTAL NEUROLOGY, 2009, 219 (01) :328-333
[3]   TRANSHEMISPHERIC DIASCHISIS - A REVIEW AND COMMENT [J].
ANDREWS, RJ .
STROKE, 1991, 22 (07) :943-949
[4]  
[Anonymous], NATL VITAL STAT REP
[5]  
[Anonymous], 1994, STROKE, DOI DOI 10.1161/01.STR.25.8.165854
[6]   Autophagy in hypoxia-ischemia induced brain injury Evidence and speculations [J].
Balduini, Walter ;
Carloni, Silvia ;
Buonocore, Giuseppe .
AUTOPHAGY, 2009, 5 (02) :221-223
[7]   PATHOPHYSIOLOGY OF ACUTE CEREBRAL-ISCHEMIA - PET STUDIES IN HUMANS [J].
BARON, JC .
CEREBROVASCULAR DISEASES, 1991, 1 :22-31
[8]   Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats [J].
Belayev, L ;
Busto, R ;
Zhao, WZ ;
Ginsberg, MD .
BRAIN RESEARCH, 1996, 739 (1-2) :88-96
[9]   EFFECT OF STEROIDS ON EDEMA AND SODIUM UPTAKE OF THE BRAIN DURING FOCAL ISCHEMIA IN RATS [J].
BETZ, AL ;
COESTER, HC .
STROKE, 1990, 21 (08) :1199-1204
[10]   Menstrual Blood Cells Display Stem Cell-Like Phenotypic Markers and Exert Neuroprotection Following Transplantation in Experimental Stroke [J].
Borlongan, Cesar V. ;
Kaneko, Yuji ;
Maki, Mina ;
Yu, Seong-Jin ;
Ali, Mohammed ;
Allickson, Julie G. ;
Sanberg, Cyndy D. ;
Kuzmin-Nichols, Nicole ;
Sanberg, Paul R. .
STEM CELLS AND DEVELOPMENT, 2010, 19 (04) :439-451