ArticleEpilepsia2009
Blood-brain barrier damage and brain penetration of antiepileptic drugs: role of serum proteins and brain edema.
Article in Epilepsia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 89 citations in OpenAlex.
- Association Between Multiple Inflammation-Derived Indices and the Risk of Post-Stroke Epilepsy.CNS neuroscience & therapeutics · 2026Article
- Mitochondrial dysfunction and NLRP3 inflammasome activation in drug-resistant epilepsy: emerging insights and mitochondrial-targeted therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Effects of valproate on the entry of inert hydrophilic markers and expression of tight junction associated genes in the neonatal brain and choroid plexus of a rat model of epilepsy (GAERS).Fluids and barriers of the CNS · 2025Article
- Study on cerebrospinal fluid meropenem, vancomycin and tigecycline monitoring in patients with central nervous system infection following neurosurgery under different drug regimens.Frontiers in pharmacology · 2025Article
- Antiseizure Medications: Advancements, Challenges, and Prospects in Drug Development.Current neuropharmacology · 2025Review
- Challenges and prospects in geriatric epilepsy treatment: the role of the blood-brain barrier in pharmacotherapy and drug delivery.Frontiers in aging neuroscience · 2024Review
- Pluronic P85 decreases the delivery of phenytoin to the brain in drug-resistant rats with P-glycoprotein overexpressed chronic mesial temporal lobe epilepsy.IBRO neuroscience reports · 2023Article
- Understanding Lamotrigine's Role in the CNS and Possible Future Evolution.International journal of molecular sciences · 2023Review
- Determination of brain water content by dry/wet weight measurement for the detection of experimental brain edema.Physiological research · 2022Article
- Membrane Vesicles Derived from Gut Microbiota and Probiotics: Cutting-Edge Therapeutic Approaches for Multidrug-Resistant Superbugs Linked to Neurological Anomalies.Pharmaceutics · 2022Review
- A sensitive LC-MS/MS method for quantification of phenytoin and its major metabolite with application to in vivo investigations of intravenous and intranasal phenytoin delivery.Journal of separation science · 2022Article
- Microvascular stabilization via blood-brain barrier regulation prevents seizure activity.Nature communications · 2022Article
- Cortical Dysplasia in Rats Provokes Neurovascular Alterations, GLUT1 Dysfunction, and Metabolic Disturbances That Are Sustained Post-Seizure Induction.Molecular neurobiology · 2022Article
- Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery.Pharmaceutics · 2022Article
- Visualization of blood-brain barrier disruption with dual-wavelength high-resolution photoacoustic microscopy.Biomedical optics express · 2022Article
- Epilepsy and Alterations of the Blood-Brain Barrier: Cause or Consequence of Epileptic Seizures or Both?Handbook of experimental pharmacology · 2022Article
- Effect of methylprednisolone on experimental brain edema in rats - own experience reviewed.Physiological research · 2021Review
- Drug Delivery Challenges in Brain Disorders across the Blood-Brain Barrier: Novel Methods and Future Considerations for Improved Therapy.Biomedicines · 2021Review
- Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury.Journal of clinical medicine · 2021Review
- Attenuation of cerebral edema facilitates recovery of glymphatic system function after status epilepticus.JCI insight · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
purposeIncreased blood-brain barrier (BBB) permeability is radiologically detectable in regions affected by drug-resistant epileptogenic lesions. Brain penetration of antiepileptic drugs (AEDs) may be affected by BBB damage. We studied the effects of BBB damage on brain distribution of hydrophilic [deoxy-glucose (DOG) and sucrose] and lipophilic (phenytoin and diazepam) molecules. We tested the hypothesis that lipophilic and hydrophilic drug distribution is differentially affected by BBB damage.
methodsIn vivo BBB disruption (BBBD) was performed in rats by intracarotid injection of hyperosmotic mannitol. Drugs (H3-sucrose, 3H-deoxy-glucose, 14C-phenytoin, and C14-diazepam) or unlabeled phenytoin was measured and correlated to brain water content and protein extravasation. In vitro hippocampal slices were exposed to different osmolarities; drug penetration and water content were assessed by analytic and densitometric methods, respectively.
resultsBBBD resulted in extravasation of serum protein and radiolabeled drugs, but was associated with no significant change in brain water. Large shifts in water content in brain slices in vitro caused a small effect on drug penetration. In both cases, total drug permeability increase was greater for lipophilic than hydrophilic compounds. BBBD reduced the amount of free phenytoin in the brain. DISCUSSION: After BBBD, drug binding to protein is the main controller of total brain drug accumulation. Osmotic BBBD increased serum protein extravasation and reduced free phenytoin brain levels. These results underlie the importance of brain environment and BBB integrity in determining drug distribution to the brain. If confirmed in drug-resistant models, these mechanisms could contribute to drug brain distribution in refractory epilepsies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.