ArticleNeurochemical research2018
Monophosphoryl Lipid A and Pam3Cys Prevent the Increase in Seizure Susceptibility and Epileptogenesis in Rats Undergoing Traumatic Brain Injury.
Article in Neurochemical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- The Toll-like receptor 1/2 ligand Pam3Cys inhibits memory impairment after traumatic brain injury in male and female rats.Scientific reports · 2026Article
- Advances and challenges in experimental models of posttraumatic epilepsy for therapeutic interventions.Pharmacological reviews · 2025Review
- Article
- Gut-microbiota-brain Axis and post-traumatic epilepsy.Epilepsia open · 2024Article
- Administration of monophosphoryl lipid A shortly after traumatic brain injury blocks the following spatial and avoidance memory loss and neuroinflammation.Scientific reports · 2024Article
- Microglial modulation as a therapeutic strategy in Alzheimer's disease: Focus on microglial preconditioning approaches.Journal of cellular and molecular medicine · 2024Review
- Epidemiology, Risk Factors, and Biomarkers of Post-Traumatic Epilepsy: A Comprehensive Overview.Biomedicines · 2024Review
- Coadministration of Monophosphoryl Lipid and Curcumin Modulates Neuroprotective Effects in LPS Stimulated Rat Primary Microglial Cells.Oxidative medicine and cellular longevity · 2024Article
- Research Progress on the Immune-Inflammatory Mechanisms of Posttraumatic Epilepsy.Cellular and molecular neurobiology · 2023Review
- Article
- Monophosphoryl Lipid A Tolerance Against Chronic Stress-Induced Depression-Like Behaviors in Mice.The international journal of neuropsychopharmacology · 2022Article
- Post-Traumatic Epilepsy and Comorbidities: Advanced Models, Molecular Mechanisms, Biomarkers, and Novel Therapeutic Interventions.Pharmacological reviews · 2022Review
- Innate immune stimulation by monophosphoryl lipid A prevents chronic social defeat stress-induced anxiety-like behaviors in mice.Journal of neuroinflammation · 2022Article
- Diversity of kindling of limbic seizures after lateral fluid percussion injury in the rat.Epilepsia open · 2021Article
- Neuropathophysiological Mechanisms and Treatment Strategies for Post-traumatic Epilepsy.Frontiers in molecular neuroscience · 2021Review
- Neuroinflammatory mechanisms of post-traumatic epilepsy.Journal of neuroinflammation · 2020Review
- The Lentiviral Vector Pseudotyped by Modified Rabies Glycoprotein Does Not Cause Reactive Gliosis and Neurodegeneration in Rat HippocampusIranian biomedical journal · 2019Article
- Prestimulation of Microglia Through TLR4 Pathway Promotes Interferon Beta Expression in a Rat Model of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2019Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Five percent of all epilepsy cases are attributed to traumatic brain injury (TBI), which are known as post-traumatic epilepsy (PTE). Finding preventive strategies for PTE is valuable. Remarkable feature of TBI is activation of microglia and subsequent neuroinflammation, which provokes epileptogenesis. The toll-like receptor agonists monophosphoryl lipid A (MPL) and tri-palmitoyl-S-glyceryl-cysteine (Pam3Cys) are safe, well-tolerated and effective adjuvants existing in prophylactic human vaccines. We examined the impact of early injection of MPL and Pam3Cys to rats, on the rate of kindled seizures acquisition following TBI. Rats received a single dose (1 µg/rat) of MPL or Pam3Cys through intracerebroventricular injection. 5 days later, trauma was exerted to temporo-parietal cortex of rats by controlled cortical impact device. After 24 h, traumatic rats underwent amygdala kindling. Brain level of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) was also measured in traumatic rats by immunoblotting. Compared to non-traumatic (sham-operated) rats, traumatic rats showed three times lower seizure threshold (133 ± 5 µA vs. 416.3 ± 16 µA, p < 0.001); about three times less number of stimuli to become kindled (5 ± 1 vs. 14 ± 2, p < 0.01); longer duration of kindled seizure parameters including entire seizure behavior, generalized seizures, and afterdischarges (p < 0.001); and a two times increase in the TNF-α level. MPL and Pam3Cys did not change kindling rate and the seizure parameters in sham-operated rats. The MPL- and Pam3Cys-pretreated traumatic rats displayed seizure threshold, speed of kindling, and duration of kindled seizure parameters, similar to the non-traumatic rats. Pretreatment by MPL and Pam3Cys prevented the increase in TNF-α level by trauma. Given that MPL and Pam3Cys currently have clinical use as well-tolerated vaccines with reliable safety, they have the potential to be used in prevention of PTE.
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