Evidence map›Paper›PMID 17645533›Full record

ArticleEpilepsia2007

In vivo and in vitro effects of pilocarpine: relevance to ictogenesis.

Nicola Marchi, Emily Oby, Ayush Batra, Laura Uva, Marco De Curtis, Nadia Hernandez, Anette Van Boxel-Dezaire, Imad Najm, Damir Janigro

Open access · bronzeAbstract read
In one paragraph

Article in Epilepsia, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 142 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Causal correlation between seizure activity and brain damage.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Review
  5. Article
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  8. Article
  9. Article
  10. Assessing seizure liabilityFrontiers in cellular neuroscience · 2023
    Article
  11. What is the Role of Lithium in Epilepsy?Current neuropharmacology · 2022
    Review
  12. Review
  13. Review
  14. Novel test strategies for in vitro seizure liability assessment.Expert opinion on drug metabolism & toxicology · 2021
    Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 3 countries.

Nicola MarchiDepartment of Cerebrovascular Research, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Emily Oby
Ayush Batra
Laura Uva
Marco De Curtis
Nadia Hernandez
Anette Van Boxel-Dezaire
Imad Najm
Damir Janigro
Fondazione IRCCS Istituto Neurologico Carlo Besta · ITInstitute of Molecular Medicine · IN

Funding

Serum markers of brain barriersR01NS049514 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI JANIGRO, DAMIR · 2006 to 2010
$1.7M
MECHANISMS OF MULTIDRUG RESISTANCER01NS043284 · NINDS · CLEVELAND CLINIC LERNER COL/MED-CWRU · PI JANIGRO, DAMIR · 2002 to 2005
$1.3M
REGULATION OF CEREBRAL BLOOD FLOW BY ATPR01HL051614 · NHLBI · CLEVELAND CLINIC FOUNDATION · PI JANIGRO, DAMIR · 2000 to 2003
$1.2M
HETEROGENEITY OF HIPPOCAMPAL GLIAR01NS038195 · NINDS · UNIVERSITY OF WASHINGTON · PI JANIGRO, DAMIR · 1999 to 2002
$574k
NHLBI NIH HHS 2R01 HL51614NHLBI NIH HHS R01 HL051614NINDS NIH HHS NS149514NINDS NIH HHS R01 NS038195NINDS NIH HHS R01 NS043284NINDS NIH HHS R01 NS049514NINDS NIH HHS R01 NS38195NINDS NIH HHS R01 NS43284
6 · The paper itself

Abstract

objectivesA common experimental model of status epilepticus (SE) utilizes intraperitoneal administration of the cholinergic agonist pilocarpine preceded by methyl-scopolamine treatment. Currently, activation of cholinergic neurons is recognized as the only factor triggering pilocarpine SE. However, cholinergic receptors are also widely distributed systemically and pretreatment with methyl-scopolamine may not be sufficient to counteract the effects of systemically injected pilocarpine. The extent of such peripheral events and the contribution to SE are unknown and the possibility that pilocarpine also induces SE by peripheral actions is yet untested.

methodsWe measured in vivo at onset of SE: brain and blood pilocarpine levels, blood-brain barrier (BBB) permeability, T-lymphocyte activation and serum levels of IL-1beta and TNF-alpha. The effects of pilocarpine on neuronal excitability was assessed in vitro on hippocampal slices or whole guinea pig brain preparations in presence of physiologic or elevated [K+](out).

resultsPilocarpine blood and brain levels at SE were 1400 +/- 200 microM and 200 +/- 80 microM, respectively. In vivo, after pilocarpine injection, increased serum IL-1beta, decreased CD4:CD8 T-lymphocyte ratios and focal BBB leakage were observed. In vitro, pilocarpine failed to exert significant synchronized epileptiform activity when applied at concentrations identical or higher to levels measured in vivo. Intense electrographic seizure-like events occurred only in the copresence of levels of K+ (6 mM) mimicking BBB leakage.

conclusionsEarly systemic events increasing BBB permeability may promote entry of cofactors (e. g. K+) into the brain leading to pilocarpine-induced SE. Disturbance of brain homeostasis represents an etiological factor contributing to pilocarpine seizures.

Indexed as

AnimalsBlood-Brain BarrierBrainDisease Models, AnimalElectroencephalographyGuinea PigsHippocampusInjections, IntraperitonealInterleukin-1betaIn Vitro TechniquesMaleMuscarinic AgonistsMuscarinic AntagonistsParasympathetic Nervous SystemPermeabilityPilocarpineInterleukin-1betaMuscarinic AgonistsMuscarinic AntagonistsPilocarpineReceptors, MuscarinicScopolamineTumor Necrosis Factor-alpha

Identifiers

PMID17645533
PMCPMC3900294
OpenAlexW2030098805

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.