Time-course investigation of blood-brain barrier permeability and tight junction protein changes in a rat model of permanent focal ischemia.

Abstract

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.

• Authors: Peng Liu, Rui Zhang, Danyang Liu, Jinling Wang, Chunling Yuan, Xuemei Zhao, Yinjie Li, Xuefei Ji, Tianyan Chi, Libo Zou
• Journal: The journal of physiological sciences : JPS (J Physiol Sci) Vol. 68 Issue 2 Pg. 121-127 (Mar 2018) ISSN: 1880-6562 [Electronic] Japan
• PMID: 28078626 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Claudin-5
• Disks Large Homolog 4 Protein
• Synaptophysin
• Tight Junction Proteins

Topics

• Animals
• Astrocytes (metabolism)
• Biological Transport (physiology)
• Biomarkers (metabolism)
• Blood-Brain Barrier (metabolism)
• Brain Ischemia (metabolism)
• Claudin-5 (metabolism)
• Disks Large Homolog 4 Protein (metabolism)
• Infarction, Middle Cerebral Artery (metabolism)
• Male
• Permeability
• Rats
• Rats, Sprague-Dawley
• Stroke (metabolism)
• Synaptophysin (metabolism)
• Tight Junction Proteins (metabolism)
• Tight Junctions (metabolism)