ABSTRACT
Identification of therapeutic targets following neurodegeneration is of major biomedical importance. Kolaviron (Kv) is a biflavonoid complex isolated from seeds of Garcina kola - a common oral masticatory agent in Nigeria known to hold medicinal value. Therefore this study evaluated the therapeutic potential of Kv on cells of the dorsolateral prefrontal cortex (DLPFC), before or after sodium azide (NaN3)-induced neurodegeneration. Rats were randomly assigned into 5 groups (6 each) and treated daily (orally) as follows: 1 ml of corn-oil (vehicle of Kv, 21 days); Kv only (200 mg/kg) for 21 days; NaN3 only (20 mg/kg for 5 days); NaN3 (20 mg/kg for 5 days) followed by Kv (200 mg/kg for 21 days); Kv (200 mg/kg for 21 days) followed by NaN3 (20 mg/kg for 5 days). After treatments, rats were sacrificed and perfused transcardially (with 4% PFA) with brains fixed in accordance with the technique to be used. The DLPFC was examined using histology (H&E), immunoperoxidase (GFAP), immunofluorescence (iNOS & nNOS) and Western blotting (MAPT, MAP2, Bax, BCL-2 and CAD). Quantitative analysis was done using ImageJ software and statistical analysis with Graphpad prism (ANOVA) at p<0.05. NaN3 treatment induced neuronal damage, characterized by reduced relative brain weight, pyknosis, karyorrhesis, astrogliosis, axonal/dendritic damage and cytoskeletal dysregualtion that subsequently resulted in increased expressions of apoptotic regulatory proteins. These degenerative changes were relatable to the observed iNOS and nNOS upregulations. However, Kv administration attenuated the NaN3- initiated destructive molecular cascades in the DLPFC of rats through mechanisms that involved inhibition of stressor molecules and toxic proteins, prevention of stress related biochemical redox, preservation of neuronal integrity, cytoskeletal framework and subsequently, reduced the level of apoptotic regulatory proteins. We conclude that Kv conferred therapeutic benefits on NaN3- induced neurodegeneration, particularly when administered before more than after the insult
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