Caveolin‐1 knockout mice are resistant to the neuroprotective effect of ischemic preconditioning

Abstract

Caveolin‐1 (Cav‐1) is thought to be a structural component of caveolae in numerous cells. Although no caveolae exist in neurons, Cav‐1 is expressed and may contribute to signaling. We recently showed the involvement of Cav‐1 in protection of isolated neurons. No studies have assessed the role of Cav‐1 in in vivo models of cerebral protection. We hypothesized that ischemic preconditioning, where a sublethal stress protect from a more lethal stress, is absent in Cav‐1 knockout mice. We induced global cerebral ischemia by bilateral carotid artery occlusion (BCAO) with cerebral blood flow (CBF) monitoring. Mice were divided into the following groups: sham, lethal ischemia (LI: BCAO for 12 min), and preconditioning (PC: BCAO for 3 min followed by 24 hr recovery prior to LI; in both wild‐type and Cav‐1 knockout mice). At 3 days following final surgery, the percent of intact CA1 neurons was calculated. Additionally, the plasticity of the posterior communicating arteries on both sides was scored. The percent of intact CA1 neuron in PC group was nearly 3‐fold higher than that in LI group (67.9 ± 7.1 %; PC, 25.8 ± 7.0 %; LI, p<0.001). However, in the PC Cav‐1 knockout mice, similar CA1 neuron loss to the LI group was observed (31.9 ± 9.7 %; PC of Cav‐1 knockout, 25.8 ± 7.0 %; LI of wild‐type, p>0.05). The minimum CBF after BCAO was correlated to the plasticity score. There was a tendency that plasticity score was increased relative to aging in Cav‐1 knockout mice. In conclusion our data suggest that 1) Cav‐1 is important to neuronal protection in vivo and 2) collateral formation appears to be linked to loss of Cav‐1 gene expression and age. Cav‐1 might serve as a unique target for neuronal preconditioning agents.