TABLE 5

Therapeutic interventions for PTE

System/FocusModelSpeciesEffect on Epileptiform ActivityDisease ModificationReference
AEDs
CarbamazepineHuman conditionClinicalNot effective for preventing or modifying seizuresN/ATemkin, 2009
PhenytoinHuman conditionClinicalNot effective for preventing or modifying seizuresN/ATemkin, 2009
PhenobarbitalHuman conditionClinicalNot effective for preventing or modifying seizuresN/ATemkin, 2009
ValproateHuman conditionClinicalNot effective for preventing or modifying seizuresN/ATemkin, 2009
CarbamazepineFPIRatNot effective for preventing or modifying seizuresN/AEastman et al., 2010
ValproateFPIRatReduced seizure frequency; reduced cumulative seizure durationN/AEastman et al., 2010
CarisbamateFPIRatNot effective for preventing or modifying seizuresN/AEastman et al., 2011
GabapentinCortical undercutRatEvoked epileptiform discharges in cortical slices 1d and 14 d post-gabapentinReduced GFAP expressionLi et al., 2012
PhenytoinPenetrating brain injuryRatReduced incidence, frequency, and duration of nonconvulsive seizures in a dose-dependent mannerNo effect on lesion volume or body weight with treatmentMountney et al., 2013
EthosuximidePenetrating brain injuryRatReduced incidence, frequency, and duration of nonconvulsive seizures in a dose-dependent mannerNo effect on lesion volume or body weight with treatmentMountney et al., 2013
LevetiracetamHuman conditionClinicalTrended with lower seizure incidence in clinical patients but never reached significanceN/AHazama et al., 2018
RetigabineCCIMouseReduced seizure susceptibility; reduced seizure frequencyReduced inflammation; lessened BBB breakdown; reduced neurodegenerationVigil et al., 2020
Inhibitory/Excitatory Pathways
Halothane (anesthetic, GABAA agonist)FPIRatNo seizures occurred while subjects were under anesthesiaN/AEastman et al., 2010
Ceftriaxone (beta-lactam antibiotic and stimulator of GLT1 expression)FPIRatReduced cumulative seizure durationPreserved GLT1 expressionGoodrich et al., 2013
Ceftriaxone (beta-lactam antibiotic and stimulator of GLT1 expression)FPIRatReduced cumulative seizure durationPreserved cortical inhibitory interneuron function with continuous treatmentHameed et al., 2019
2-deoxyglucose (glycolysis inhibitor)CCIMouseRestored excitatory and inhibitory synaptic activity; reduced epileptiform activityReduced neurodegeneration of PV+ interneuronsKoenig et al., 2019
Imidizodiazepine KRM-II-81 (selective for alpha2/3 containing GABAAR)CCIMouseReduced hyperactivityN/AWitkin et al., 2020
mTOR pathway
RapamycinCCICD1 mouseReduced seizure incidence (13% versus 50%); reduced seizure frequency; lessened behavioral component of seizuresReduced neurodegeneration; attenuated mossy fiber sproutingGuo et al., 2013
RapamycinCCIMouseReduced seizure frequencyReduced neurodegeneration; attenuated mossy fiber sprouting; stabilized neurogenesisButler et al., 2015
RapamycinCCIMouseModified synaptic and tonic GABAAR-mediated currents.N/AButler et al., 2016
Inflammation
MinozacCCICD1 miceReduced seizure susceptibilityReduced inflammation; improved cognitive impairmentsChrzaszcz et al., 2010
Kineret (IL-1R antagonist)CCIPediatric mouseReduced seizure susceptibilityImproved neuropathology; improved cognitive impairmentsSemple et al., 2017
Monophosphoryl lipid A and Pam3CysCCI; kindlingRatReduced seizure susceptibility; slowed kindling rateReduced TNF-alpha brain levelsHesam et al., 2018
Glycyrrhizin (HMGB1 inhibitor)CCIPediatric mouseNot effective for preventing or modifying seizuresReduced HMGB1 brain levels, edema, and microglial activationWebster et al., 2019
Plasticity
BDNF blocker (TrkB-Fc)Ex vivo Schaffer collateral lesions in organotypic hippocampal slice culturesPediatric mouseReduced hyperexcitability of CA3 neuronsAttenuate mossy fiber sproutingGill et al., 2013
LM22A-4 (partial agonist of TrkB)Cortical UndercutRatDecreased incidence of epileptiform dischargesIncreased parvalbumin immunoreactivityGu et al., 2018
PTX BD4-3 (partial agonist of TrkB)Cortical UndercutRatReduced PTZ susceptibility.N/AGu et al., 2018
Hypothermia
HypothermiaFPIRatReduced PTZ susceptibilityAttenuate mossy fiber sprouting; did not exhibit neuroprotective effects on cell lossAtkins et al., 2010
HypothermiaFPIRatAbolished ictal activity up to 10 weeks after hypothermia treatmentN/AD'Ambrosio et al., 2013
Electrical Stimulation
Deep Brain StimulationHuman ConditionClinicalReduced seizure frequencyN/APiacentino et al., 2018
Hyperphosphorylation of Tau
Sodium SelenateFPIRatIncreased latency to seizures/epileptiform activityAmeliorated enlargement of ventricles and hippocampal atrophyLiu et al., 2016.
Cell Transplantation Therapy
Cell transplantation therapy (GABAergic progenitors from medial ganglionic eminence)CCIMouseReduced incidence of PTEImproved cognitive impairments;Zhu et al., 2019
Other
Rimonabant CB1R antagonist 1 or 10 mg/kg immediately or 20min after TBIFPIRatReduced KA susceptibilityN/AEchegoyen et al., 2009
Ketogenic DietFPIRatNot effective for preventing or modifying seizuresN/ASchwartzkroin et al., 2010
CreatineFPIRatNot effective for preventing or modifying seizuresReduced oxidative stress markersSaraiva et al., 2012
Exercise (Treadmill)FPIRatLengthened latency to seizures; reduced seizure duration; reduced PTZ susceptibilityN/ASilva et al., 2013
C-10068 (Dextromethorphan Derivative)PBBIRatLengthen latency to seizures; reduced seizure frequency, reduced cumulative seizure durationReduced inflammationLu et al., 2015
Atipamezole, Alpha2 Adrenergic Receptor AntagonistFPIRatReduced PTZ susceptibilityImproved functional recoveryNissinen et al., 2017
Creatine Supplementation, May Be Needed Long-Term; 300mg/kg P.O. 4 wksFPIRatLengthened latency to seizures; decreased duration of tonic-clonic seizures; reduced PTZ-induced epileptiform dischargesReduced neurodegenerationGerbatin et al., 2019
ProgesteroneWeight dropRatReduced length of PTZ-induced seizures; lessened behavioral component of seizuresN/AGhadiri et al., 2019