Time-course investigation of blood–brain barrier permeability and tight junction protein changes in a rat model of permanent focal ischemia
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Permanent middle cerebral artery occlusion (pMCAO) is an animal model that is widely used to simulate human ischemic stroke. However, the timing of the changes in the expression of tight junction (TJ) proteins and synaptic proteins associated with pMCAO remain incompletely understood. Therefore, to further explore the characteristics and mechanisms of blood–brain barrier (BBB) damage during cerebral ischemic stroke, we used a pMCAO rat model to define dynamic changes in BBB permeability within 120 h after ischemia in order to examine the expression levels of the TJ proteins claudin-5 and occludin and the synaptic proteins synaptophysin (SYP) and postsynaptic density protein 95 (PSD95). In our study, Evans blue content began to increase at 4 h and was highest at 8 and 120 h after ischemia. TTC staining showed that cerebral infarction was observed at 4 h and that the percentage of infarct volume increased with time after ischemia. The expression levels of claudin-5 and occludin began to decline at 1 h and were lowest at 8 and 120 h after ischemia. The expression levels of SYP and PSD95 decreased from 12 to 120 h after ischemia. GFAP, an astrocyte marker, gradually increased in the cortex penumbra over time post-ischemia. Our study helps clarify the characteristics of pMCAO models and provides evidence supporting the translational potential of animal stroke models.
KeywordsCerebral ischemia Blood–brain barrier Tight junctions pMCAO
This work was supported by the Career Development Program for Young Teachers in Shenyang Pharmaceutical University (No. ZQN2015028), the National Natural Science Foundation of China (81503057) and the Key Laboratory for Neurodegenerative Diseases of Ministry of Education (Capital Medical University) (1300-1150170609).
Compliance with ethical standards
All animal procedures performed in this study were approved by the Institute for Experimental Animals at Shenyang Pharmaceutical University (Permit Number: SYPU-IACUC-C2015-0831-203).
Conflict of interest
The authors declare that they have no conflicts of interest.
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