An Increase of Sigma-1 Receptor in the Penumbra Neuron after Acute Ischemic Stroke

Abstract

Background: Penumbra salvage from infarction by early reperfusion within the time window is the target of acute ischemic stroke therapies. Although the penumbral imaging is potently usable in clinic trial, additional work needs to be performed to advancing the field with better-defined, evaluated, and validated imaging measures.

Methods: Mice were subjected to permanent stroke by right middle cerebral artery (MCA) occlusion. Multimodel magnetic resonance imaging (MRI) method was assessed to define the penumbra as that brain region in which the perfusion and diffusion-weighted MR images are mismatched (perfusion-weighted imaging [PWI]-diffusion-weighted imaging [DWI] mismatch). MRI measurements were performed at 1 hour after MCA occlusion (MCAO). Sigma-1 receptor expression was assessed by immunoblotting and immunostaining in PWI-DWI-defined penumbra and core compared with sham or contralateral slice. Penumbral sigma-1 receptor identified the correlation with the neuron, astrocyte, and microglia by immuno-colocalization.

Results: Sigma-1 receptor was significantly upregulated in penumbra or peri-infarct compared with sham and core tissue at 1 hour and 24 hours after MCAO. There was a colocalization of sigma-1 receptor and neuron in penumbra at 1 hour after stroke. Sigma-1 receptor is specifically increased in ischemic penumbral neuron at 1 hour after MCAO.

Conclusions: Sigma-1 receptor may act as an endogenous marker of penumbra after acute ischemic stroke.

Keywords: Sigma-1 receptor; diffusion-weighted imaging; ischemic stroke; magnetic resonance imaging; mice; perfusion-weighted imaging.