Intranasal Cerebrolysin Improves Cognitive Function and Structural Synaptic Plasticity in Photothrombotic Mouse Model of Medial Prefrontal Cortex Ischemia

Medial prefrontal cortex (mPFC) ischemia affects post-stroke cognitive outcomes. We aimed to investigate the effects of different doses and routes of cerebrolysin (CBL) on the structural synaptic plasticity and cognitive function after mPFC ischemia in mice. Thence, CBL (1, 2.5 ml/kg/i.p./daily) or (1 ml/kg/i.n./daily), were administrated in photothrombotic mouse model of mPFC ischemia for two weeks. Episodic and spatial memories were assessed by the What-Where-Which (WWWhich) and Barnes tasks. Growth-associated protein 43 (GAP-43), postsynaptic density-95 (PSD-95), and synaptophysin (SYN) levels were measured in the lesioned area using western blot analysis. Dendritic arbors, spine densities, and morphology were assessed via Golgi-Cox staining. Treatment with 2.5 ml/kg/i.p. and 1 ml/kg/i.n. doses attenuated mPFC ischemia-induced episodic and spatial memories impairment. Results showed an obvious increase in the GAP-43, PSD-95 and SYN levels and improvement in the structural synaptic indexes in lesioned area induced by the same doses and routes of CBL. In conclusion, we found that specific doses/routes of CBL have positive effects on the structural synaptic plasticity and cognitive outcomes after mPFC ischemia.