TABLE 5.
Therapeutic interventions for PTE
| System/Focus | Model | Species | Effect on Epileptiform Activity | Disease Modification | Reference |
|---|---|---|---|---|---|
| AEDs | |||||
| Carbamazepine | Human condition | Clinical | Not effective for preventing or modifying seizures | N/A | Temkin, 2009 |
| Phenytoin | Human condition | Clinical | Not effective for preventing or modifying seizures | N/A | Temkin, 2009 |
| Phenobarbital | Human condition | Clinical | Not effective for preventing or modifying seizures | N/A | Temkin, 2009 |
| Valproate | Human condition | Clinical | Not effective for preventing or modifying seizures | N/A | Temkin, 2009 |
| Carbamazepine | FPI | Rat | Not effective for preventing or modifying seizures | N/A | Eastman et al., 2010 |
| Valproate | FPI | Rat | Reduced seizure frequency; reduced cumulative seizure duration | N/A | Eastman et al., 2010 |
| Carisbamate | FPI | Rat | Not effective for preventing or modifying seizures | N/A | Eastman et al., 2011 |
| Gabapentin | Cortical undercut | Rat | Evoked epileptiform discharges in cortical slices 1d and 14 d post-gabapentin | Reduced GFAP expression | Li et al., 2012 |
| Phenytoin | Penetrating brain injury | Rat | Reduced incidence, frequency, and duration of nonconvulsive seizures in a dose-dependent manner | No effect on lesion volume or body weight with treatment | Mountney et al., 2013 |
| Ethosuximide | Penetrating brain injury | Rat | Reduced incidence, frequency, and duration of nonconvulsive seizures in a dose-dependent manner | No effect on lesion volume or body weight with treatment | Mountney et al., 2013 |
| Levetiracetam | Human condition | Clinical | Trended with lower seizure incidence in clinical patients but never reached significance | N/A | Hazama et al., 2018 |
| Retigabine | CCI | Mouse | Reduced seizure susceptibility; reduced seizure frequency | Reduced inflammation; lessened BBB breakdown; reduced neurodegeneration | Vigil et al., 2020 |
| Inhibitory/Excitatory Pathways | |||||
| Halothane (anesthetic, GABAA agonist) | FPI | Rat | No seizures occurred while subjects were under anesthesia | N/A | Eastman et al., 2010 |
| Ceftriaxone (beta-lactam antibiotic and stimulator of GLT1 expression) | FPI | Rat | Reduced cumulative seizure duration | Preserved GLT1 expression | Goodrich et al., 2013 |
| Ceftriaxone (beta-lactam antibiotic and stimulator of GLT1 expression) | FPI | Rat | Reduced cumulative seizure duration | Preserved cortical inhibitory interneuron function with continuous treatment | Hameed et al., 2019 |
| 2-deoxyglucose (glycolysis inhibitor) | CCI | Mouse | Restored excitatory and inhibitory synaptic activity; reduced epileptiform activity | Reduced neurodegeneration of PV+ interneurons | Koenig et al., 2019 |
| Imidizodiazepine KRM-II-81 (selective for alpha2/3 containing GABAAR) | CCI | Mouse | Reduced hyperactivity | N/A | Witkin et al., 2020 |
| mTOR pathway | |||||
| Rapamycin | CCI | CD1 mouse | Reduced seizure incidence (13% versus 50%); reduced seizure frequency; lessened behavioral component of seizures | Reduced neurodegeneration; attenuated mossy fiber sprouting | Guo et al., 2013 |
| Rapamycin | CCI | Mouse | Reduced seizure frequency | Reduced neurodegeneration; attenuated mossy fiber sprouting; stabilized neurogenesis | Butler et al., 2015 |
| Rapamycin | CCI | Mouse | Modified synaptic and tonic GABAAR-mediated currents. | N/A | Butler et al., 2016 |
| Inflammation | |||||
| Minozac | CCI | CD1 mice | Reduced seizure susceptibility | Reduced inflammation; improved cognitive impairments | Chrzaszcz et al., 2010 |
| Kineret (IL-1R antagonist) | CCI | Pediatric mouse | Reduced seizure susceptibility | Improved neuropathology; improved cognitive impairments | Semple et al., 2017 |
| Monophosphoryl lipid A and Pam3Cys | CCI; kindling | Rat | Reduced seizure susceptibility; slowed kindling rate | Reduced TNF-alpha brain levels | Hesam et al., 2018 |
| Glycyrrhizin (HMGB1 inhibitor) | CCI | Pediatric mouse | Not effective for preventing or modifying seizures | Reduced HMGB1 brain levels, edema, and microglial activation | Webster et al., 2019 |
| Plasticity | |||||
| BDNF blocker (TrkB-Fc) | Ex vivo Schaffer collateral lesions in organotypic hippocampal slice cultures | Pediatric mouse | Reduced hyperexcitability of CA3 neurons | Attenuate mossy fiber sprouting | Gill et al., 2013 |
| LM22A-4 (partial agonist of TrkB) | Cortical Undercut | Rat | Decreased incidence of epileptiform discharges | Increased parvalbumin immunoreactivity | Gu et al., 2018 |
| PTX BD4-3 (partial agonist of TrkB) | Cortical Undercut | Rat | Reduced PTZ susceptibility. | N/A | Gu et al., 2018 |
| Hypothermia | |||||
| Hypothermia | FPI | Rat | Reduced PTZ susceptibility | Attenuate mossy fiber sprouting; did not exhibit neuroprotective effects on cell loss | Atkins et al., 2010 |
| Hypothermia | FPI | Rat | Abolished ictal activity up to 10 weeks after hypothermia treatment | N/A | D'Ambrosio et al., 2013 |
| Electrical Stimulation | |||||
| Deep Brain Stimulation | Human Condition | Clinical | Reduced seizure frequency | N/A | Piacentino et al., 2018 |
| Hyperphosphorylation of Tau | |||||
| Sodium Selenate | FPI | Rat | Increased latency to seizures/epileptiform activity | Ameliorated enlargement of ventricles and hippocampal atrophy | Liu et al., 2016. |
| Cell Transplantation Therapy | |||||
| Cell transplantation therapy (GABAergic progenitors from medial ganglionic eminence) | CCI | Mouse | Reduced incidence of PTE | Improved cognitive impairments; | Zhu et al., 2019 |
| Other | |||||
| Rimonabant CB1R antagonist 1 or 10 mg/kg immediately or 20min after TBI | FPI | Rat | Reduced KA susceptibility | N/A | Echegoyen et al., 2009 |
| Ketogenic Diet | FPI | Rat | Not effective for preventing or modifying seizures | N/A | Schwartzkroin et al., 2010 |
| Creatine | FPI | Rat | Not effective for preventing or modifying seizures | Reduced oxidative stress markers | Saraiva et al., 2012 |
| Exercise (Treadmill) | FPI | Rat | Lengthened latency to seizures; reduced seizure duration; reduced PTZ susceptibility | N/A | Silva et al., 2013 |
| C-10068 (Dextromethorphan Derivative) | PBBI | Rat | Lengthen latency to seizures; reduced seizure frequency, reduced cumulative seizure duration | Reduced inflammation | Lu et al., 2015 |
| Atipamezole, Alpha2 Adrenergic Receptor Antagonist | FPI | Rat | Reduced PTZ susceptibility | Improved functional recovery | Nissinen et al., 2017 |
| Creatine Supplementation, May Be Needed Long-Term; 300mg/kg P.O. 4 wks | FPI | Rat | Lengthened latency to seizures; decreased duration of tonic-clonic seizures; reduced PTZ-induced epileptiform discharges | Reduced neurodegeneration | Gerbatin et al., 2019 |
| Progesterone | Weight drop | Rat | Reduced length of PTZ-induced seizures; lessened behavioral component of seizures | N/A | Ghadiri et al., 2019 |