directly into the CNS, GRASP, and GDF15 were infused in 1 μL
volumes into the fourth ventricle (4th ICV). All systemic treatments
were delivered by intraperitoneal (IP) injection. For central administration,
GDF15 (human recombinant, Biovision, cat. 4569) was dissolved at a
concentration of 30 pmol/μL in 100% dimethyl sulfoxide (DMSO).
For systemic treatments, GDF15 was dissolved in a 5 mM acetate salt,
240 mM propylene glycol, and 0.007% polysorbate 20, in a pH 4 saline
solution and injected at a dose of 20 μg/kg (1 mL/kg). For central
administration, GRASP was dissolved in artificial cerebrospinal fluid
(aCSF; Harvard Apparatus) and injected at 300 and 3000 pmol concentrations.
Systemically delivered GRASP was dissolved in 0.9% saline and injected
in a volume of 1 mL/kg at 30 and 100 nmol/kg. Cisplatin (Cis, cis-diammineplatinum dichloride, Sigma-Aldrich) was dissolved
in 0.9% saline and administered at a dose of 6 mg/kg. The selective
5-HT3R antagonist Ondansetron (Tocris) was dissolved in
0.9% saline and IP was injected at 2 mg/kg (1 mL/kg). GDF15, GRASP,
and/or Ondansetron were administered IP at 1 mL/kg, and cisplatin
was administered IP at 6 mL/kg. Fluorescently tagged GDF15 and GRASP
were dissolved in aCSF (300 pmol/μL); 1 μL was infused
into the lateral ventricle (LV ICV).