Nitro-aspirin (NCX4016) reduces brain damage induced by focal cerebral ischemia in the rat

The potential neuroprotective effects of the novel nitro-derivate of aspiri n (NCX4016) on permanent focal cerebral ischemia in spontaneously hypertens ive rats (SHRs) was investigated. Reference compounds were acetylsalicilic acid (ASA) and FK506 (tacrolimus), Ten minutes after surgery, SHRs were ran domly divided into four groups of ten, pharmacologically treated and sacrif iced 24 h after treatment. Brains were removed and processed to measure inf arct volume, 70 kDa heat shock protein (hsp70), glial fibrillary acidic pro tein (GFAP) and vimentin (Vim) immunoreactivity (IR), and apoptosis using t erminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick e nd-labeling (TUNEL) assay. NCX-4016 significantly reduced total infarct vol ume compared to ASA (-20%, P < 0.05), FK506 (-18%, P < 9.05) and vehicle tr eatment (-20%, P < 0.05). Experimental groups did not differ in hsp70-IR an d GFAP-IR. Conversely, hyperplastic astrocytes, measured by Vim-IR, were si gnificantly lower in NCX-4016 than in the vehicle group (-36%, P < 0.01). T UNEL assay indicated a significantly lower degree of apoptosis in NCX-4016 group than vehicle in both the homolateral (-27%, P < 0.01) and contralater al hemisphere (-29%, P < 0.05). These findings indicate that NO release ass ociated with aspirin confers neuroprotective effects against ischemic injur y. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.