Cav-1 Protein Levels in Serum and Infarcted Brain Correlate with Hemorrhagic Volume in a Mouse Model of Thromboembolic Stroke, Independently of rt-PA Administration

Abstract

Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is currently the only FDAapproved drug for acute ischemic stroke. However, its administration is still limited due to the associated increased risk of hemorrhagic transformation (HT). rt-PA may exacerbate blood-brain barrier (BBB) injury by several mechanisms that have not been fully elucidated. Caveolin-1 (Cav-1), a major structural protein of caveolae, has been linked to the endothelial barrier function. The effects of rt-PA on Cav-1 expression remains largely unknown. Here, Cav-1 protein expression after ischemic conditions, with or without rt-PA administration, was analyzed in a murine thromboembolic middle cerebral artery occlusion (MCAO) and in brain microvascular endothelial bEnd.3 cells subjected to oxygen/glucose deprivation (OGD). Our results show that Cav-1 is overexpressed in endothelial cells after ischemia in both models. rtPA signi cantly reduced Cav-1 expression and increases pCav-1/Cav-1 ratio in bEnd.3 cells, but not in the in vivo model. In addition, we rst show that increased Cav-1 immunoreactivity in the infarcted area and Cav-1 serum levels are positively correlated at 24 h post-MCAO. Interestingly, Cav-1 expression in infarcted area and baseline serum Cav-1 levels negatively correlate with hemorrhagic volume, supporting a protective role of Cav-1 in cerebral ischemia and pointing to a potential usefulness of baseline serum Cav-1 levels as predictor of hemorrhagic volume, independently of rt-PA administration.

Inhibiting Caveolin-1-Related Akt/mTOR Signaling Pathway Protects Against N-methyl-D-Aspartate Receptor Activation-Mediated Dysfunction of Blood–Brain Barrier in vitro

“…It has been suggested that phosphorylation of Cav-1 may contribute early BBB breakdown [ 31 ]. NMDA induced neurotoxicity is directly related to the activation of the Akt/mTOR signaling pathway [ 32 ].…”

Effect of Clopidogrel combined with aspirin in the treatment of acute progressive cerebral infarction: A retrospective single-center analysis

“…Increases in its level lead to the enlargement of edema zones around the infarcted site and aggravate the disease. 22 Thus, the combination therapy may improve the efficacy of APCI treatments by reducing serum levels of VILIP-1 and Cav-1.…”

Caveolin-1 Promoted Collateral Vessel Formation in Patients With Moyamoya Disease

“…Studies from mouse ischemic stroke model demonstrated that Cav-1 immunoreactivity is significantly and specifically increased in the endothelial cells in the infarcted area 24 h post-MCA occlusion (MCAO). Serum Cav-1 is positively correlated with Cav-1 immunoreactivity of the brain ( 26 ). Accumulating evidence pointed out that Cav-1 was expressed in human brain microvascular endothelial cells and smooth muscle cells ( 8 , 27 ).…”