Pinealectomy: behavioral and neuropathological consequences in a chronic cerebral hypoperfusion model

This experiment determined if pinealectomy (PX) affects the consequences of chronic, moderate brain ischemia. Rats were pinealectomized at 25 days of age and trained at 9 months on a tactile radial maze. They then underwent permanent occlusion of the common carotid arteries (2VO) or sham surgery, followed by maze retraining and then neurohistological assessment at 16 months. Combined PX + 2VO rats committed more working memory errors on the maze. 2VO itself caused a 10% reduction in hippocampal CA1 pyramidal cell number. PX alone caused a 21% reduction. Combined PX and 2VO caused the greatest reduction (32%) of CA1 cells. Similar results were seen for CA4. PX also increased glial fibrillary acidic protein immunoreactivity in both CA1 and CA4. Thus PX not only augmented the consequences of chronic brain ischemia but notably, PX itself caused hippocampal damage. These effects seemed not to result from the small cortical lesion caused by the PX procedure. The results are consistent with the hypothesis that endogenous melatonin is a neuroprotectant in the aging brain.