Chronic In Vivo Imaging of a Focal Cortical Dysplasia Mouse Model Reveals Progressive Neuronal Loss with No Senolytic or Antiseizure Efficacy Following Dasatinib-Quercetin Treatment

In a mosaic MTORp.L2427P focal cortical dysplasia mouse model, longitudinal two-photon imaging showed progressive loss of labeled mTORmut (16.7%) and non-mTORmut (13.1%) neurons over eight weeks.

• Why it matters: A reported dasatinib-quercetin senolytic and antiseizure effect in an Mtorp.S2215F model has not been validated in a second FCD model, leaving uncertainty about whether neuron elimination generalizes.
• What they did: Chronic cranial windows and longitudinal two-photon imaging tracked genetically labeled neurons for eight weeks in 47 C57BL/6J MTORp.L2427P mice, with continuous video-EEG, IHC, and LC-MS/MS pharmacokinetics; seizure testing was extended to a Swiss/CD1 cohort.
• The result: Oral DQ showed no evidence of eliminating dysmorphic neurons or reducing seizure frequency, duration, or burden in either strain, despite B-Gal+ cell density tending to decrease; brain dasatinib (median 8.5 nM) exceeded Src/ABL IC50 while quercetin (median 12 nM) was far below BCL-XL affinity.