Lestaurtinib (CEP-701) reduces the duration of limbic status epilepticus in periadolescent rats.
Epilepsy Res
; 195: 107198, 2023 09.
Article
in En
| MEDLINE
| ID: mdl-37467703
ABSTRACT
BACKGROUND:
The timely abortion of status epilepticus (SE) is essential to avoid brain damage and long-term neurodevelopmental sequalae. However, available anti-seizure treatments fail to abort SE in 30% of children. Given the role of the tropomyosin-related kinase B (TrkB) receptor in hyperexcitability, we investigated if TrkB blockade with lestaurtinib (CEP-701) enhances the response of SE to a standard treatment protocol and reduces SE-related brain injury.METHODS:
SE was induced with intra-amygdalar kainic acid in postnatal day 45 rats under continuous electroencephalogram (EEG). Fifteen min post-SE onset, rats received intraperitoneal (i.p.) CEP-701 (KCEP group) or its vehicle (KV group). Controls received CEP-701 or its vehicle following intra-amygdalar saline. All groups received two i.p. doses of diazepam, followed by i.p. levetiracetam at 15 min intervals post-SE onset. Hippocampal TrkB dimer to monomer ratios were assessed by immunoblot 24 hr post-SE, along with neuronal densities and glial fibrillary acid protein (GFAP) levels.RESULTS:
SE duration was 50% shorter in the KCEP group compared to KV (p < 0.05). Compared to controls, SE induced a 1.5-fold increase in TrkB dimerization in KV rats (p < 0.05), but not in KCEP rats which were comparable to controls (p > 0.05). The KCEP group had lower GFAP levels than KV (p < 0.05), and both were higher than controls (p < 0.05). KCEP and KV rats had comparable hippocampal neuronal densities (p > 0.05), and both were lower than controls (p < 0.05).CONCLUSIONS:
Given its established human safety, CEP-701 is a promising adjuvant drug for the timely abortion of SE and the attenuation of SE-related brain injury.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Status Epilepticus
/
Brain Injuries
Type of study:
Guideline
Limits:
Animals
/
Child
/
Humans
Language:
En
Journal:
Epilepsy Res
Journal subject:
CEREBRO
/
NEUROLOGIA
Year:
2023
Type:
Article
Affiliation country:
Lebanon