Journal Article


D C Henshall
R P Simon
J H M Prehn
W Taki
S Matsushima
N Murphy
C Bonner
R Meller
E M Jimenez-Mateos
C Bellver-Estelles
and 1 others



male disease models animal physiology oligonucleotide array sequence analysis ischemic preconditioning kainic acid mice inbred c57bl animals excitatory amino acid agonists etiology mice complications gene expression profiling rna messenger epilepsy brain damage chronic therapeutic use nerve tissue proteins convulsants therapy nerve degeneration gene expression physiopathology prevention control down regulation genetics hippocampus metabolism status epilepticus up regulation treatment outcome

Microarray profile of seizure damage-refractory hippocampal CA3 in a mouse model of epileptic preconditioning. (2007)

Abstract A neuroprotected state can be acquired by preconditioning brain with a stimulus that is subthreshold for damage (tolerance). Acquisition of tolerance involves coordinate, bi-directional changes to gene expression levels and the re-programmed phenotype is determined by the preconditioning stimulus. While best studied in ischemic brain there is evidence brief seizures can confer tolerance against prolonged seizures (status epilepticus). Presently, we developed a model of epileptic preconditioning in mice and used microarrays to gain insight into the transcriptional phenotype within the target hippocampus at the time tolerance had been acquired. Epileptic tolerance was induced by an episode of non-damaging seizures in adult C57Bl/6 mice using a systemic injection of kainic acid. Neuron and DNA damage-positive cell counts 24 h after status epilepticus induced by intraamygdala microinjection of kainic acid revealed preconditioning given 24 h prior reduced CA3 neuronal death by approximately 45% compared with non-tolerant seizure mice. Microarray analysis of over 39,000 transcripts (Affymetrix 430 2.0 chip) from microdissected CA3 subfields was undertaken at the point at which tolerance was acquired. Results revealed a unique profile of small numbers of equivalently up- and down-regulated genes with biological functions that included transport and localization, ubiquitin metabolism, apoptosis and cell cycle control. Select microarray findings were validated post hoc by real-time polymerase chain reaction and Western blotting. The present study defines a paradigm for inducing epileptic preconditioning in mice and first insight into the global transcriptome of the seizure-damage refractory brain.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

D C Henshall, R P Simon, J H M Prehn, W Taki, S Matsushima, N Murphy, C Bonner, R Meller, E M Jimenez-Mateos, C Bellver-Estelles and 1 others

Experts in our system

David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
Eva M Jimenez-Mateos
Royal College of Surgeons in Ireland
Total Publications: 55