S. Fredduzzi et al., Nitro-aspirin (NCX4016) reduces brain damage induced by focal cerebral ischemia in the rat, NEUROSCI L, 302(2-3), 2001, pp. 121-124
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.