Learning impairment and microtubule-associated protein 2 decrease in gerbils under chronic cerebral hypoperfusion.

A coiled stainless steel wire clip was made that allowed us to chronically reduce cerebral blood flow in Mongolian gerbils. After 6 weeks of reduced cerebral blood flow in 15 experimental gerbils, we evaluated their learning ability and found it to be impaired relative to that in 15 control gerbils. Eight weeks after surgery, regional cerebral blood flow in the parietal cortex measured by the hydrogen clearance method in the experimental gerbils was 73-76% of that in the control gerbils. Light microscopy showed minimal histologic changes in the brains of the experimental gerbils. Concentrations of brain proteins analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that among water-soluble brain proteins, the concentrations of cytoskeletal proteins (microtubule-associated protein 2, calspectin, and clathrin) declined in the experimental gerbils. In particular, the concentration of microtubule-associated protein 2 declined significantly. Our findings show that the reduction of cerebral blood flow via carotid stenosis impairs the learning behavior in gerbils, with an associated decrease in the concentration of microtubule-associated protein 2. We believe that Mongolian gerbils with chronically reduced cerebral blood flow are a useful animal model of chronic brain hypoperfusion.