Upregulation of membrane‐bound metalloendopeptidase neurolysin in a mouse model of focal brain ischemia

Abstract

Membrane‐bound metalloendopeptidase neurolysin was recently identified as the non‐AT1, non‐AT2 angiotensin binding site. Our previous study indicated dramatic over‐expression of this protein in membrane preparations of primary cortical neurons challenged in several in vitro models of cell death suggesting a possible role of neurolysin in neuronal survival. To further confirm the association between upregulation of neurolysin and neuronal cell death, in this work we studied the changes in density of membrane‐bound neurolysin in mouse transient middle cerebral artery occlusion model (60 min occlusion with ~75% local cerebral blood flow drop, followed by 24 h reperfusion). Brain parts were collected after documenting reperfusion injury by neurological scoring and TTC staining. Density of neurolsyin was estimated by radioligand binding assays in cerebral cortical, striatal, hippocampal and cerebellar membranes from ischemic hemispheres. Membrane preparations of the same brain parts from sham operated mice served as controls. Significant up‐regulation of neurolysin in membrane preparations of all forebrain regions from ischemic brains was observed. Density of neurolysin did not differ in cerebellar membranes of ischemic and control brains. These results confirm our in vitro observations further supporting a role of neurolsyin in neuronal cell death. Supported by TTUHSC SOP start‐up funds to VTK.