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@ARTICLE{Wormuth:271084,
author = {Wormuth, Carola and Papazoglou, Anna and Henseler,
Christina and Ehninger, Dan and Broich, Karl and Haenisch,
Britta and Hescheler, Jürgen and Köhling, Rüdiger and
Weiergräber, Marco},
title = {{A} {N}ovel {R}at {I}nfant {M}odel of {M}edial {T}emporal
{L}obe {E}pilepsy {R}eveals {N}ew {I}nsight into the
{M}olecular {B}iology and {E}pileptogenesis in the
{D}eveloping {B}rain.},
journal = {Neural plasticity},
volume = {2024},
number = {1},
issn = {2090-5904},
address = {New York, NY},
publisher = {Hindawi},
reportid = {DZNE-2024-00956},
pages = {9946769},
year = {2024},
abstract = {Although several adult rat models of medial temporal lobe
epilepsy (mTLE) have been described in detail, our knowledge
of mTLE epileptogenesis in infant rats is limited. Here, we
present a novel infant rat model of mTLE (InfRPil-mTLE)
based on a repetitive, triphasic injection regimen
consisting of low-dose pilocarpine administrations (180
mg/kg. i.p.) on days 9, 11, and 15 post partum (pp). The
model had a survival rate of $>80\%$ and exhibited
characteristic spontaneous recurrent electrographic seizures
(SRES) in both the hippocampus and cortex that persisted
into adulthood. Using implantable video-EEG radiotelemetry,
we quantified a complex set of seizure parameters that
demonstrated the induction of chronic
electroencephalographic seizure activity in our InfRPil-mTLE
model, which predominated during the dark cycle. We further
analyzed selected candidate genes potentially relevant to
epileptogenesis using a RT-qPCR approach. Several
candidates, such as the low-voltage-activated Ca2+ channel
Cav3.2 and the auxiliary subunits β 1 and β 2, which were
previously reported to be upregulated in the hippocampus of
the adult pilocarpine mTLE model, were found to be
downregulated (together with Cav2.1, Cav2.3, M1, and M3) in
the hippocampus and cortex of our InfRPil-mTLE model. From a
translational point of view, our model could serve as a
blueprint for childhood epileptic disorders and further
contribute to antiepileptic drug research and development in
the future.},
keywords = {Animals / Epilepsy, Temporal Lobe: physiopathology /
Epilepsy, Temporal Lobe: genetics / Epilepsy, Temporal Lobe:
metabolism / Epilepsy, Temporal Lobe: chemically induced /
Disease Models, Animal / Rats / Pilocarpine /
Electroencephalography / Hippocampus: metabolism / Animals,
Newborn / Brain: metabolism / Rats, Sprague-Dawley / Male /
Female / Pilocarpine (NLM Chemicals)},
cin = {AG Ehninger / AG Hänisch},
ddc = {610},
cid = {I:(DE-2719)1013005 / I:(DE-2719)1013010},
pnm = {352 - Disease Mechanisms (POF4-352) / 354 - Disease
Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39104708},
pmc = {pmc:PMC11300100},
doi = {10.1155/2024/9946769},
url = {https://pub.dzne.de/record/271084},
}