mPFC hemorrhage induces hippocampal CA1 dendritic spine plasticity and attentional deficits in mice.

Background and purpose: Damage to a specific brain region, in addition to its local effects, can influence brain function by inducing neuroplasticity in remote areas. This study hypothesized that hemorrhage of the medial prefrontal cortex (mPFC) is associated with deficits in shifting attention through structural alterations in the hippocampal CA1 region, an area with known functional connections to the mPFC. Experimental approach: C57BL/6 mice were subjected to intracerebral hemorrhage (ICH) or sham surgery. Neurological function was assessed using the neurological deficit score (NDS) on different days after injury, and cognitive flexibility was evaluated using the attentional set shifting task (AST) over a 17-day protocol. Structural changes were examined by assessing white matter and dendritic spine density using Luxol fast blue (LFB) and Golgi staining techniques on brain tissue. Statistical analysis was performed with SPSS-26. Findings/Results: No significant difference was observed in NDS between the groups. Mice with ICH demonstrated a lower task completion rate, along with an increased number of trials and set-loss errors in the AST. Dendritic spine density in the CA1 region was higher in the ICH group compared to the sham group, particularly in the right hemisphere, but no significant changes were noted in the white matter. Conclusion and implications: The observed results following mPFC injury indicated an association between cortical damage, hippocampal plasticity, and cognitive dysfunction, consequently identifying hippocampal plasticity as a potential target for future therapeutic strategies aimed at improving post-stroke cognitive recovery.