Intranasal Autologous Conditioned Serum Attenuates Memory Impairment After mPFC Ischemia in Mice

Globally, stroke ranks as the second most prevalent cause of death, contributing significantly to worldwide mortality burdens, imposing a significant economic and emotional challenge on societies. This study was designed to investigate the effect of autologous conditioned serum (ACS) on memory and associated molecular factors in a mouse model of photothrombotic ischemic stroke.

The photothrombotic model was used to induce medial prefrontal cortex (mPFC) ischemia. ACS were prepared by intracardiac puncture of C57BL/6 mice using special ACS syringes. After blood incubation, the sample was centrifuged, and the serum was analyzed with ELISA kits to quantify the levels of interleukin-1 receptor antagonist (IL-1RA) and insulin-like growth factor (IGF-I). The ischemic animals received 48 μL intranasal ACS two times a day, once a day, or once every other day for one week. Behavioral tests, including the Lashley-III maze and social interaction test, were conducted following treatment administration. Additionally, IGF-1, IL-1β, IL-1RA levels, and phospho-tau/total-tau ratio were measured in the mPFC area by western blot. Histological analysis was performed to assess ischemic volume.

The results indicated that once-daily administration of ACS significantly improved spatial memory in the Lashley-III maze and showed a notable enhancement in social memory as measured by the social interaction test. In terms of molecular analysis, ACS increased the levels of IGF-1 and IL-1RA, whilst decreasing the levels of IL-1β and p-tau/total-tau ratio.

In conclusion, post-stroke intranasal ACS administration enhances memory, possibly by increasing the level of IGF-1 and attenuating inflammation through the inhibition of IL-1β signal by IL-1RA, and regulation of tau levels.