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.

Focal, but not global, cerebral ischaemia causes loss of myenteric neurons and upregulation of vasoactive intestinal peptide in mouse ileum

“…Several authors have reported that pMCAO and GCIR cause disruption of the neurovascular barrier (Liu et al . ,b), while it remains intact after CCH (Farkas et al . ).…”

“…Postoperative pain relief was by subcutaneous administration of Marcainâ (1.25 mg/ kg). The endpoint of each model was set in regard to the central neuronal injury (Mracsk o et al 2010;Cheng et al 2016;Svensson et al 2016;Liu et al 2017b), and no impact on enteric neurons is to be expected until after the brain injury.…”

Total Glycosides of Cistanche deserticola Promote Neurological Function Recovery by Inducing Neurovascular Regeneration via Nrf-2/Keap-1 Pathway in MCAO/R Rats

“…Among them, ZO-1, claudin-5, and occludin are the most important proteins in TJs. Mounting evidence indicates that the increased permeability of BBB induced by ischemia generally correlates with the alterations of ZO-1, claudin-5, and occludin (Cao et al, 2016a;Page et al, 2016;Yu et al, 2017;Liu et al, 2018). In this work, the results demonstrated that although TGs could significantly increase the expressions of ZO-1, claudin-5, and occludin proteins in MCAO-induced brain tissues, neither PSs nor OSs did.…”

Protein kinase C is involved in the neuroprotective effect of berberine against intrastriatal injection of quinolinic acid‐induced biochemical alteration in mice

“…Triphenyltetrazolium chloride staining was performed as described in our previous report . After behavioural test, the mice were killed and the brains were sectioned at the QA‐injected position and stained with 2% solution of TTC at 37°C in the dark for 20 minutes.…”