COX-2 and NeuN double stains 24 hours and one week after tMCAo. The COX-2 IHC was developed with nickel-enhanced DAB (black), whereas NeuN was visualized with NovaRed® (brownish red). The images 5A and 5B are obtained from a pilot study where the animal was euthanized 24 hours after tMCAo. 5A visualizes a relatively small neocortical infarct in the right hemisphere. The box delineates a part of the ischemic border zone that is shown at forty times magnification in 5B. The penumbra contains large swollen neurons that express the membrane-bound COX-2 enzyme. In the infarct core the neurons tend to be small and star-shaped due to irreversible neuronal death. 5C and 5E are from a saline-treated animal one week after tMCAo. Forty times magnifications of the boxes are shown in 5D and 5F. The neurons in the border zone on Day 8 after ischemic injury showed a perinuclear expression pattern of the COX-2 enzyme (5D). COX-2+ neurons can be found in areas like the neocortex, piriform cortex and the DG of the hippocampus under normal conditions. 5F shows COX-2 expressed in dendrites of neurons in the molecular cell layer of the DG. The scale bar in 5A is 5 mm, whereas the scale bars in 5B, 5D and 5F equals 50 μm.