TABLE 1.
Effects of anti-inflammatory therapeutics in OP models.
| OP model | Pretreatments | Therapeutic class | Therapeutic agent | Dosing regimen | Outcome | References |
|---|---|---|---|---|---|---|
| Rat—Sarin (108 ug/kg, i.m.) | None | NSAID | Indomethacin Ibuprofen | 10 mg/kg, at onset of convulsions | ↑ seizure severity | Chapman et al. (2019) |
| Rat—Sarin (108 ug/kg, i.m.) | None | Steroid | Methylprednisolone Dexamethasone | 20 mg/kg, at onset of convulsions | ↑ seizure severity | Chapman et al. (2019) |
| Rat—Sarin (108 ug/kg, i.m.) | None | Steroid | Methylprednisolone Dexamethasone | 20 mg/kg ip at 4, 20 hr after sarin | No improvement in clinical seizure severity or PGE2 levels at 24 and 48 h. | Chapman et al. (2019) |
| Rat—Sarin (108ug/kg, i.m.) | None | COX-2 Inhibitor | Nimesulide | 6 mg/kg at 4, 20 h after sarin | ↓ TNFa, PGE2, IL1B, and IL6 expression at 8 and 24 h; | Chapman et al. (2019) |
| No improvement to neuropathology. | ||||||
| Rat—Sarin (108 ug/kg, i.m.) | None | COX inhibitor | Ibuprofen | 10 mg/kg at 4, 20 h after sarin | ↓ IL6 expression at 24 h; | Chapman et al. (2019) |
| No improvement to neuropathology. | ||||||
| Rat—Sarin (108 ug/kg, i.m.) | None | Phospholipase A2 Inhibitor | Quinacrine | 5 mg/kg at 4, 20 h after sarin | ↓ IL1B and IL6 expression at 24 h; | Chapman et al. (2019) |
| No improvement to neuropathology. | ||||||
| Rat—Sarin (108 ug/kg, i.m.) | None | PGE Analogue | Ilomedin Prostin Misoprostol | Immediately after sarin, again at 2 hr after sarin | ↓ TNFa, IL1B, and IL6 expression at 24 h; | Chapman et al. (2019) |
| Prostin and misoprostol ↓ TSPO expression at 24 h; | ||||||
| At 7 d, all-or-none reduction in TSPO. | ||||||
| Rat—Soman (154 ug/kg, s.c.) | 30 m asoxime chloride (125 mg/kg, i.m.) | Antioxidant | AEOL10150 | 7 mg/kg, s.c. 1, 5, or 15 min after SE onset, repeated every 4 h | ↓ oxidative stress, microglial activation, neurodegeneration, and proinflammatory cytokine expression at 24 h. | Liang et al., (2019) |
| Rat—Soman (180 ug/kg, s.c.) | 30 m asoxime chloride (125 mg/kg, i.m.) | Immune modulator | Poly-YE | 1 mg/kg, s.c. 24 h post intoxication | ↓ neurodegeneration and microglial activation in the piriform cortex at 28 d; | Finkelstein et al. (2012) |
| No significant improvements in Barnes Maze performance. | ||||||
| Rat—DFP (9.5 mg/kg, i.p.) | 30 m with pyridostigmine bromide (0.1 mg/kg, s.c.), 10 m with atropine methylbromide (20 mg/kg, s.c.) | EP2 receptor antagonist | TG6-10–1 | 5 mg/kg, i.p. | Treatment iii) ↓ delayed mortality, ↑ weight gain, ↓ transcription of cytokines/chemokines, ↓ IBA1 mRNA and immunolabeling, ↓ FJB in CA1 at 4 d. | Rojas et al. (2015) |
| i) 1 h prior to DFP; | ||||||
| ii) two injections (4 and 21 h after SE-onset); | ||||||
| iii) six injections (80–150 min, 5–6 h, 9–21 h, 31–42 h, and 48 hr after SE-onset) | ||||||
| Rat—DFP (9.5 mg/kg, i.p.) | 30 m with pyridostigmine bromide (0.1 mg/kg, s.c.), 10 m with atropine methylbromide (20 mg/kg, s.c.) | EP2 receptor antagonist | TG6-10–1 | 5 mg/kg, i.p. | Treatment iii) improved discrimination in the NOR at 4 w post intoxication. | Rojas et al. (2016) |
| i) 1 h prior to DFP; | ||||||
| ii) three injections (1.5, 6, 21 h after SE-onset); | ||||||
| iii) six injections (1.5, 6, 21, 30, 45–47, and 52–55 h after SE-onset) | ||||||
| Rat—DFP (4 mg/kg, s.c.) | None | iNOS inhibitor | 1400 W | 20 mg/kg every 12 h for 3 d | ↓ GFAP and IBA1 cells at 7 d; | Putra et al. (2019) |
| ↓ incidence, duration, and frequency of SRS over 12 w; | ||||||
| ↓ reactive astrogliosis and microgliosis at 12 w. | ||||||
| Rat—DFP (4.5 mg/kg, s.c.) | 30 m pyridostigmine (0.1 mg/kg, i.m.) | Antioxidant | AEOL10150 | 5 mg/kg s.c. 5 min into SE, repeated every 4 h | ↓ proinflammatory mediators at 24 h. | Liang et al. (2018) |
| Rat—DFP (5 mg/kg, i.p.) | None | Immune modulator | Naltrexone | 5 mg/kg starting 1 h post intoxication, repeated daily. | Reduced learning deficits over 4 w post intoxication. | Brewer et al. (2013) |
| Rat—DFP (9 mg/kg, i.p.) | 30 m pyridostigmine bromide (0.1 mg/kg, i.m.), 10 m atropine methylnitrate (20 mg/kg, i.m.) | Growth factor | Neuregulin-1 (NRG-1) | 3.2 ug/kg, internal carotid artery | Treatment i) at 24 h ↓ neurodegeneration and oxidative stress; ↓ shifts in microglia activation; ↓ expression of proinflammatory cytokines; | Li et al. (2012); Li et al. (2015) |
| i) 5 min pretreatment; | Treatment ii) ↓ neurodegeneration at 24 h. | |||||
| ii) post-treatment 1 hr after DFP intoxication; | ||||||
| iii) post-treatment 4 h after DFP intoxication | ||||||
| Rat—DFP (4 mg/kg, s.c.) | None | Antioxidant | Diapocynin (DPO) | 300 mg/kg, p.o., six doses, 12 h intervals beginning 2 h post-DFP | Mitigates motor deficits at 18 d; | Putra et al. (2020) |
| ↓ astrogliosis, neurodegeneration, and inflammatory cytokine expression at 6 w. | ||||||
| Rat—Paraoxon (0.45 mg/kg, i.m.) | None | Immune modulator | Poly-YE | 1 mg/kg, s.c. 24 h post intoxication | ↓ neurodegeneration in the piriform cortex and amygdala at 28 d; | Finkelstein et al. (2012) |
| ↓ microglial activation and ↑ BDNF in the piriform cortex at 28 d. |
DFP, diisopropylfluorophosphate; TMB4, trimedoxime bromide; MDZ, midazolam; AMN, atropine methyl nitrate; AS, atropine sulfate; 2-PAM, pralidoxime; SE, status epilepticus; ↑, increase; ↓, decrease; FJB, Fluoro-Jade B; NOR, novel object recognition.