Prophylactic effects of treatment with various drug categories on the long-term consequences of SE in rats
Only studies in which treatment started after onset of SE are included. If studies were performed in immature rats, this is indicated in the Model column.
| Drug | Model (Induction of SE) | SE duration (Limited by) | Beginning of Prophylactic Treatment with Test Drug | Duration of Prophylactic Treatment | Consequences of Prophylactic Drug Treatment | Reference | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Latency to SRS | Incidence of SRS | Frequency, Severity, or Duration of SRS | Neurodegeneration | Behavioral Alterations (Psychopathology) | Impairment of Learning and Memory | ||||||
| Neuroprotective | |||||||||||
| Ketamin* (NMDA antagonist) | Pilocarpine | 2 h (Clonazepam) | 15 min (K15) or 120 min (K120) after SE onset | 1 dose | N.D. | ↓ (K15) | N.D. | ↓ (Ca1, Ca3) (K15>K120) | N.D. | ↓ (K15> K120) | Hort et al., 1999* |
| Ketamin | Pilocarpine (in hippocampus) | 3 h (Thiopental) | 1 h after 3 h SE | 4 days | N.D. | N.D. | N.D. | ↓ (CA1, CA3, hilus) | N.D. | ↓ | Cunha et al., 2009 |
| MK-801* (NMDA antagonist) | Hippocampal stimulation | Not limited in controls | 1, 2 or 4 h after SE onset | 1 dose | N.D. | ↓ (only for the 1 and 2 h after SE onset groups) | N.D. | N.D. | N.D. | N.D. | Prasad et al., 2001* |
| MK-801 | Kainate | 1.5 h (Diazepam) | 90 min after SE onset | 1 dose | N.D. | N.E. | N.E. | ↓ (CA1, CA3, PC, thalamus) | N.D. | N.D. | Brandt et al., 2003b |
| MK-801 | Lithium-pilocarpine | 1.5 h (Diazepam) | 90 min after SE onset | 1 dose | N.D. | N.D. | N.D. | ↓ (CA1, CA3, PC, SN) | N.D. | N.D. | Bankstahl et al., 2008 |
| NS1209* (AMPA antagonist) | Amygdala stimulation | Not limited in controls | 2–3 h after SE onset | 1 dose or infusion for 24 h | N.D. | N.D. | N.D. | ↓ (Hippocampus) | N.D. | N.D. | Pitkänen et al., 2007b* |
| DEVD (caspase-3 inhibitor) | Kainate | 1.5 h (Diazepam) | 1.5 h and 24 h after SE onset | 2 doses | N.D. | N.D. | N.D. | N.E. (Hippocampus) | N.D. | N.D. | Ebert et al., 2002 |
| z-DEVD-fmk (caspase-3 inhibitor) | Amygdala stimulation | 3 h (Diazepam) | 3 h after SE onset | 1 week | N.D. | ↓ (At 8–11 weeks after SE) | N.E. | ↓ (CA3 and hilus) | N.D. | N.E. | Narkilahti et al., 2003 |
| Erythropoietin | Pilocarpine | 2 h (Diazepam) | 0.5 h after SE | Additional doses at 1 and 3 days affter SE | N.D. | N.D. | N.D. | ↓ (CA1, CA3 and hilus) | N.D. | N.D. | Nadam et al., 2007 |
| Erythropoietin | Lithium-pilocarpine | 1 h (Diazepam) | 1 h after SE onset | 1 week | N.D. | N.E. | ↓ | ↓ (CA1, CA3, hilus) | N.D. | N.D. | Chu et al., 2008 |
| FGF-2 and BDNF gene therapy | Pilocarpine | 2 h (Diazepam) | 4 days after SE | 1 Unilateral injection into hippocampus | N.E. | ↓ (In 20% of rats) | ↓ | No neuroprotective effect, but partial repair by increased neurogenesis (hippocampus) | N.D. | N.D. | Paradiso et al., 2009 |
| Anti-inflammatory | |||||||||||
| Celecoxib (COX-2 inhibitor) | Lithium-pilocarpine | 1 h (Diazepam) | 1 day after SE | 2 weeks | N.D. | ↓ | ↓ | ↓ (CA1, CA3, hilus) | N.D. | N.D. | Jung et al., 2006 |
| SC58236 (COX-2 inhibitor) | Hippocampus stimulation | 4 h (Isoflurane) | 4 h after SE | 7 days | N.D. | N.E. | N.E. | N.E. (Hilus) | N.D. | N.D. | Holtman et al., 2009 |
| Parecoxib | Lithium-pilocarpine | 1.5 h (Diazepam) | 1.5 h after SE onset | 18 days | N.D. | N.E. | ↓ | ↓ (CA1, PC) | (↓) | (↓) | Polascheck et al., 2010 (A) |
| α4 integrin specific monoclonal antibody | Pilocarpine (mice) | 2 h (Diazepam) | 1 h after SE | 20 days | N.E. | N.E. | ↓ | ↓ | ↓ | N.D. | Fabene et al., 2008 |
| Immunosuppressive | |||||||||||
| Rapamycin | Kainate | Not limited | 24 h after SE | 6 weeks | N.D. | N.E. | ↓ | N.E. (CA1, CA3, hilus) | N.D. | N.D. | Zeng et al., 2009 |
| Rapamycin | Pilocarpine | 2 h (Diazepam) | 1–8 h after termination of SE | 1–2 months | N.D. | N.D. | N.D. | N.E. (Hilus) | N.D. | N.D. | Buckmaster et al., 2009 |
| FK506 (tacrolimus) | Amygdala stimulation | Not indicated | 24 h after SE | 2 weeks | Decreased | Increased | Increased | N.D. | N.D. | N.D. | Lukasiuk and Sliwa, 2009 (A) |
| FK506 (tacrolimus) | Pilocarpine | Not limited | At time of generalized convulsive SE | 1 dose | N.D. | N.D. | N.D. | ↓ | N.D. | N.D. | Chwiej et al., 2010 |
| Neuromodulatory | |||||||||||
| Atipamezole (α2 antagonist) | Amygdala stimulation | Exp. 1: 3 h (diazepam); Exp. 2:not limited | 7 days after SE | 9 weeks | N.D. | N.E. | ↓ | ↓ (Hilus) | N.D. | N.E. | Pitkänen et al., 2004 |
| Rimonabant (CB1 antagonist) | Kainate | Not limited | Immediate after SE onset | 1 dose | N.E. | N.E. | N.E. | N.D. | N.D. | N.D. | Pouliot et al., 2009 (A) |
| Bumetanide | Lithium-Pilocarpine | 1.5 h (Diazepam + phenobarbital) | 90 min after SE onset | 5 days | N.E. | N.E. | N.E. | N.E. | N.E. | N.D. | Brandt et al., 2010 |
| Bumetanide + phenobarbital | Lithium-pilocarpine | 1.5 h (Diazepam + phenobarbital) | 90 min after SE onset | 5–14 days | Increased | N.E. | ↓ | N.E. (?) | ↓ | N.D. | Brandt et al., 2010 |
↵↓, A prophylactic (beneficial) effect; *, studies in which treatment effects were due to initial insult modification (i.e., reduction of SE duration or severity) rather than an antiepileptogenic effect (see text for discussion); (A), studies that are available only as abstracts.
EC, entorhinal cortex; FGF, fibroblast growth factor; K, ketamine; N.D., not determined; N.E., no effect; P, postnatal day; PC, piriform cortex; PPS, perforant path stimulation; SN, substantia nigra; SRS, spontaneous recurrent seizures; z-DEVD-fmk, N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethyl ketone.