Insight into Drug Resistance in Status Epilepticus: Evidence from Animal Models
Abstract
:1. Introduction
2. Current Dilemmas in Pharmacological Treatment
3. Animal Models of SE
3.1. KA-Induced SE Model
3.2. Pilocarpine-Induced SE Model
3.3. Kindling-Induced SE Model
3.4. Prolonged FS-Induced SE Model
3.5. Other SE Models
4. Common Hypotheses of Drug-Resistant SE
4.1. Degraded GABAergic Transmission Hypothesis
4.2. Augment of AMPA Receptor Function Hypothesis
4.3. Overactivation of Neuroinflammation Hypothesis
4.4. Upregulated P-glycoprotein (P-gp) Hypothesis
4.5. Neurotrophic Factors (NTFs) Hypothesis
5. Summary and Outlook
- (1)
- New Mechanism of SE in both molecular and circuit levels
- (2)
- New smart therapeutics with safe and effective features
- (3)
- Prediction of drug resistance in SE
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
SE | Status epilepticus |
ILAE | International League Against Epilepsy |
AED | Antiepileptic drug |
EEG | Electroencephalogram |
KA | Kainic acid |
FS | Febrile seizure |
CNS | Central nervous system |
RSE | Refractory status epilepticus |
SRSE | Super-refractory status epilepticus |
NMDA | N-methyl-D-aspartic acid |
GABA | γ-aminobutyric acid |
LPS | Lipopolysaccharide |
AMPAR | α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor |
IL-1β | Interleukin-1β |
HMGB1 | High mobility group box 1 |
TLR4 | Toll-like receptor 4 |
NF-κB | Nuclear factor kappa-B |
P-gp | P-glycoprotein |
COX-2 | Cyclooxygenase-2 |
NTFs | Neurotrophic factors |
BDNF | Brain-derived neurotrophic factor |
FGF2 | Fibroblast growth factor 2 |
TrkB | Tropomyosin-related kinase B |
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Model | Mode of Operation | Mechanism | Mortality Rate |
---|---|---|---|
KA model | Intraperitoneal injection | KA binds directly to non-NMDA (KA) receptors in the neuronal postsynaptic membrane, producing excitatory postsynaptic potentials that lead to seizures. | 47–75% |
Intraventricular injection | 8–21% | ||
Intranasal injection | Lower than intraventricular injection | ||
Pilocarpine model | Lithium–pilocarpine | Pilocarpine can stimulate not only the M receptor, but also NMDA receptors, metabolic glutamate receptors, resulting in activation of the excitatory system in the brain. | 27.4–40% |
Intracerebral administration | |||
Kindling model | Hippocampus | Repeated electrical stimulations cause a gradual change in the excitatory synaptic plasticity and lower seizure threshold. | —— |
Amygdala | |||
Prolonged FS | LPS-induced FS | An imbalance between the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter GABA. | About 50% |
Heat-induced FS | |||
FS induced by heat combined with LPS |
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Wang, F.; Zhang, Q.; Wang, Y.; Chen, J.; Wang, Y. Insight into Drug Resistance in Status Epilepticus: Evidence from Animal Models. Int. J. Mol. Sci. 2023, 24, 2039. https://doi.org/10.3390/ijms24032039
Wang F, Zhang Q, Wang Y, Chen J, Wang Y. Insight into Drug Resistance in Status Epilepticus: Evidence from Animal Models. International Journal of Molecular Sciences. 2023; 24(3):2039. https://doi.org/10.3390/ijms24032039
Chicago/Turabian StyleWang, Fei, Qingyang Zhang, Yu Wang, Junzi Chen, and Yi Wang. 2023. "Insight into Drug Resistance in Status Epilepticus: Evidence from Animal Models" International Journal of Molecular Sciences 24, no. 3: 2039. https://doi.org/10.3390/ijms24032039