Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental animal models of ischemic stroke.

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants

Infarct volume.

<p>TTC staining (A-N) in the sham-, vehicle-pre- and post-, 10 and 20 mg/kg ASA, DA and ASA-DA-ischemia-group at 48 h after ischemia-reperfusion. In the vehicle-ischemia-group, infarct areas are apparent. Only in the 20 mg/kg ASA-DA-pre-ischemia-group, the infarct area is notably decreased. Percentage change in infarct volume (O) (n = 7 per group; *P < 0.05, significantly different from the sham-group, #P < 0.05, significantly different from the vehicle-ischemia-group; +P < 0.05, significantly different from the corresponding same treated -group). The bars indicate the means ± SD.</p

Rotarod test and PET-CT imaging.

<p>Rotarod test (A) and PET-CT imaging (B) in the sham-, vehicle-, ASA-DA-pre-ischemia-groups. Only pretreatment with 20 mg/kg ASA-DA significantly ameliorates motor activity and impaired glucose metabolism (asterisks) (n = 7 per group; *P < 0.05, significantly different from the sham-group, #P < 0.05, significantly different from the vehicle-ischemia-group). The bars indicate the means ± SD.</p

Synthesis of ASA-DA.

<p>Synthesis of ASA-DA.</p

NeuN immunohistochemistry and F-J B histofluorescence.

<p>NeuN immunohistochemistry (A-E) and F-J B histofluorescence (F-J) in the CA1 region of the vehicle-sham-, vehicle-ischemia-, 10 and 20 mg/kg ASA-DA-pre-ischemia-groups at 5 days after ischemia-reperfusion. NeuN immunoreactivity is easily detected in the stratum pyramidale (SP) of the CA1 region of the vehicle-sham- and 20 mg/kg ASA-DA-pre-ischemia-groups. In the vehicle-ischemia- and 10 mg/kg ASA-DA-pre-ischemia-groups, many F-J B+ cells are detected in the SP (asterisks). Relative analysis (E and J) as percent in the mean number of NeuN+ and F-J B+ cells in the CA1 region (n = 7 per group; *P < 0.05, significantly different from the vehicle- sham-group, #P < 0.05, significantly different from the vehicle-ischemia-group). The bars indicate the means ± SD.</p

GFAP (A), Iba-1 (B), SOD1 (C), SOD2 (D), CAT (E) and Gpx (F) immunohistochemistry.

<p>All of them in the CA1 region of the vehicle- and 20 mg/kg ASA-DA-pre-ischemia-groups at sham, 2 and 5 days after ischemia-reperfusion. In the vehicle-ischemia-group at 5 days post-ischemia, GFAP immunoreactivity increases in all the layers, and Iba-1 immunoreactivity is aggregated in the stratum pyramidale (SP). In the 20 mg/kg ASA-DA-pre-ischemia-group at 5 days post-ischemia, GFAP and Iba-1 immunoreactivity are much lower than those in the vehicle-ischemia-group at 5 days post-ischemia-group. In the vehicle-ischemia-group at 5 days post-ischemia, SOD1, 2, CAT and Gpx immunoreactivity are weakly detected in the stratum pyramidale. However, their immunoreactivity is well maintained or increased in the stratum pyramidale of the 20 mg/kg ASA-DA-ischemia-group at 5 days post-ischemia. SO; stratum oriens, SR; stratum radiatum. Scale bar = 50 µm.</p