Morris Water Maze

“Three-month-old male p16-3MR mice received PTX (5 mg/kg/day, i.p., n = 150) or vehicle (DMSO + saline, n = 50) in 2 cycles (5 days/cycle) with a 7-day interval between cycles”

“Mice were left to recover for 2 weeks in the original environment”

“PTX treated mice were assigned randomly to three groups. Two groups received the senolytic drug ABT263 or ganciclovir (GCV)”

“Two groups received the senolytic drug ABT263 (Navitoclax, Chemgood, C-1009, i.p., 1.5 mg/kg/daily in DMSO/saline)”

“ganciclovir (GCV [TSZCHEM, RG001, >99%]; i.p. 25 mg/kg/daily) for 5 days and 2 cycles with a 2 week interval between cycles”

“The third group served as vehicle controls”

“spatial memory and long term memory were tested by assessing performance in the radial arms water maze at 6 months post-chemotherapy”

“Hippocampal-dependent contextual memory was tested with the Y-maze two-trial delayed alternation task”

“grip strength test was used to measure the maximal muscle strength of mouse forelimbs”

“Motor coordination was assessed using an automated four-lane rotarod tool”

“automated computer assisted method (CatWalk; Noldus Information Technology Inc.)”

“mice were equipped with a chronic cranial window and intravital two-photon microscopy-based and optical coherence tomography (OCT) based imaging methods were used”

“To assess BBB permeability and cerebromicrovascular density, mice were equipped with a chronic cranial window and intravital two-photon microscopy-based and optical coherence tomography (OCT) based imaging methods were used”

“mice in each group were anesthetized with isoflurane (2% induction and 1% maintenance), endotracheally intubated, and ventilated”

“The skull was thinned and changes in cerebral blood flow (CBF) were assessed above the left somatosensory whisker barrel cortex in response to mechanical stimulation of the right whiskers”

“CBF responses to whisker stimulation were repeated after administrating the nitric oxide synthase inhibitor N ω-Nitro-L-arginine methyl ester”

“Flow cytometric detection of RFP+/CD-31+ senescent endothelial cells, RFP-/CD-31+ non-senescent endothelial cells”

“single-cell transcriptomics”

“At the end of 6 months after the PTX protocol, mice were tested for cognitive functions, NVC responses, and microvascular density and BBB integrity, and then were euthanized for tissue collection”