Table 3:
Multiple Dose Neuropathology Results
| Compound | Dose mg/kg | Route of administration | % animals with vacuolization | % animals with necrosis | % animals with increased Iba-1 labelling | % animals with increased GFAP staining | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 3h | 363 h | 432 h | 3 h | 363 h | 432 h | 3h | 363 h | 432 h | 3h | 363 h | 432 h | |||
| Negative control | NA | IVa | 0% | 0% | 0% | 0% | ||||||||
| (2R,6R)-HNK | 12 | IVa | 0% | 0% | 0% | 0% | ||||||||
| (2R,6R)-HNK | 80 | IVa | 0% | 0% | 0% | 0% | ||||||||
| (2R,6R)-HNK | 160 | IVa | 0% | 0% | 0% | 0% | ||||||||
| Ketamine | 50 | IPb | 0% | 0% | 0% | 0% | ||||||||
| Ketamine | 60 | IPb | 0% | 0% | 0% | 0% | ||||||||
| MK-801 | 0.5 | SCc | 0% | 0% | 0% | 0% | 60% | 40% | 0% | 70% | 10% | 0% | 80% | 80% |
| MK-801 | 0.8 | SCc | 30% | 0% | 0% | 0% | 100% | 90% | 0% | 90% | 40% | 0% | 100% | 100% |
Ten animals/sex/group per timepoint per sex were utilized. The negative control and (2R,6R)-HNK groups utilized both male and female animals. The ketamine andMK-801 groups utilized only female animals.363 hours represents Day 15, + 3 hours. 432 hours represents Day 15 + 72 hours
Administered as an intravenous infusion over 20 minutes.
Intraperitoneal injection.
Subcutaneous dosing.