thus, injury severity might influence the ability to detect treatment-related effects. For all canine buy Apigenin studies, GM6001 was dissolved in 90% DMSO at a concentration of 250 mg/mL. The solution was sterilized using a 25-mm syringe filter with 0.22-mm HT Tuffryn membrane. Dogs, participating in the drug tolerance study, were acclimatized for 14 days and then randomized as follows: DMSO, 100 mg/kg GM6001, 150 mg/kg GM6001, or 300 mg/kg GM6001 subcutaneously every 12 hours for 3 days. The doses of GM6001 were selected to exceed those reported previously in a murine model of SCI. A SC route of administration was selected as 1) GM6001 does not remain solubilized in DMSO when exposed to hydrophilic solutions such as blood, prohibiting intravenous delivery and 2) intraperitoneal drug administration is not generally permitted in client-owned dogs at our institution, due to challenges in managing any local drug reactions. Adverse event monitoring was performed for 7 days following the completion of drug administration. All dogs had physical examinations, injection site evaluations, and assessment of food and water intake twice daily. A complete blood count, serum biochemistry profile, urinalysis, and coagulation profile were performed 3 and 7 days following the completion of drug administration. Following the completion of this study, the vehicle and 300 mg/kg GM6001 dogs were euthanized via intravenous administration of 120 mg/kg pentobarbital. The brain, heart, liver, kidney, lung, intestine, and injection sites were evaluated. Immediately after collection of CSF and blood, dogs were randomized to receive 100 mg/kg GM6001+ DMSO, DMSO, or saline placebo. The dose of both DMSO and saline was 0.4 mL/ kg, a volume equivalent to that of 100 mg/kg GM6001+DMSO; this approach was taken to maintain blinding. A randomization 1000413-72-8 sequence was developed prior to the initiation of this trial and randomization was accomplished by blocking the dogs by gender status in a 1:1:1 ratio to each of the treatment groups. Sealed envelopes contained treatment allocations and were delivered to a central location where treatments were formulated by individuals not involved in the