title: Nitro-aspirin (NCX4016) reduces brain damage induced by focal cerebral ischemia in the rat.
abstract: The potential neuroprotective effects of the novel nitro-derivate of aspirin (NCX4016) on permanent focal cerebral ischemia in spontaneously hypertensive rats (SHRs) was investigated. Reference compounds were acetylsalicilic acid (ASA) and FK506 (tacrolimus). Ten minutes after surgery, SHRs were randomly divided into four groups of ten, pharmacologically treated and sacrificed 24 h after treatment. Brains were removed and processed to measure infarct volume, 70 kDa heat shock protein (hsp70), glial fibrillary acidic protein (GFAP) and vimentin (Vim) immunoreactivity (IR), and apoptosis using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay. NCX-4016 significantly reduced total infarct volume compared to ASA (-20%, P < 0.05), FK506 (-18%, P < 0.05) and vehicle treatment (-20%, P < 0.05). Experimental groups did not differ in hsp70-IR and GFAP-IR. Conversely, hyperplastic astrocytes, measured by Vim-IR, were significantly lower in NCX-4016 than in the vehicle group (-36%, P<0.01). TUNEL assay indicated a significantly lower degree of apoptosis in NCX-4016 group than vehicle in both the homolateral (-27%, P < 0.01) and contralateral hemisphere (-29%, P < 0.05). These findings indicate that NO release associated with aspirin confers neuroprotective effects against ischemic injury.
authors: Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Sezione di Biologia Sperimentale, Via del Giochetto, 06124, Perugia, Italy.
authors: S
authors: S
authors: Fredduzzi
authors: G
authors: G
authors: Mariucci
authors: M
authors: M
authors: Tantucci
authors: P
authors: P
authors: Del Soldato
authors: M V
authors: MV
authors: Ambrosini
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D016559:Tacrolimus / Q000494:pharmacology; D014746:Vimentin / Q000187:drug effects / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005904:Glial Fibrillary Acidic Protein; D018840:HSP70 Heat-Shock Proteins; D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D014746:Vimentin; C102148:nitroaspirin; D001241:Aspirin; D016559:Tacrolimus