Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat model of epilepsy: implications for understanding presymptomatic epileptogenesis, predictive diagnosis, and targeted treatments

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Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat model of epilepsy : implications for understanding presymptomatic epileptogenesis, predictive diagnosis, and targeted treatments. / Bernard, Paul B; Ramsay, Leslie A; MacDonald, Debra S; Tasker, R Andrew.

In: The EPMA journal, Vol. 8, No. 3, 09.2017, p. 247-254.

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@article{4e93624781e041a2a9e8579ea72aecf8,
title = "Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat model of epilepsy: implications for understanding presymptomatic epileptogenesis, predictive diagnosis, and targeted treatments",
abstract = "Epilepsies affect about 4{\%} of the population and are frequently characterized by a prolonged {"}silent{"} period before the onset of spontaneous seizures. Most current animal models of epilepsy either involve acute seizure induction or kindling protocols that induce repetitive seizures. We have developed a rat model of epilepsy that is characterized by a slowly progressing series of behavioral abnormalities prior to the onset of behavioral seizures. In the current study, we further describe an accompanying progression of cytoarchitectural changes in the hippocampal formation. Groups of male and female SD rats received serial injections of a low dose of domoic acid (0.020 mg/kg) (or vehicle) throughout the second week of life. Postmortem hippocampal tissue was obtained on postnatal days 29, 64, and 90 and processed for glial fibrillary acidic protein (GFAP), NeuN, and calbindin expression. The data revealed no significant changes on postnatal day (PND) 29 but a significant increase in hilar NeuN-positive cells in some regions on PND 64 and 90 that were identified as ectopic granule cells. Further, an increase in GFAP positive cell counts and evidence of reactive astrogliosis was found on PND 90 but not at earlier time points. We conclude that changes in cellular expression, possibly due to on-going non-convulsive seizures, develop slowly in this model and may contribute to progressive brain dysfunction that culminates in a seizure-prone phenotype.",
keywords = "Journal Article",
author = "Bernard, {Paul B} and Ramsay, {Leslie A} and MacDonald, {Debra S} and Tasker, {R Andrew}",
year = "2017",
month = "9",
doi = "10.1007/s13167-017-0111-9",
language = "English",
volume = "8",
pages = "247--254",
journal = "The EPMA journal",
issn = "1878-5077",
publisher = "BioMed Central Ltd.",
number = "3",

}

RIS

TY - JOUR

T1 - Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat model of epilepsy

T2 - implications for understanding presymptomatic epileptogenesis, predictive diagnosis, and targeted treatments

AU - Bernard, Paul B

AU - Ramsay, Leslie A

AU - MacDonald, Debra S

AU - Tasker, R Andrew

PY - 2017/9

Y1 - 2017/9

N2 - Epilepsies affect about 4% of the population and are frequently characterized by a prolonged "silent" period before the onset of spontaneous seizures. Most current animal models of epilepsy either involve acute seizure induction or kindling protocols that induce repetitive seizures. We have developed a rat model of epilepsy that is characterized by a slowly progressing series of behavioral abnormalities prior to the onset of behavioral seizures. In the current study, we further describe an accompanying progression of cytoarchitectural changes in the hippocampal formation. Groups of male and female SD rats received serial injections of a low dose of domoic acid (0.020 mg/kg) (or vehicle) throughout the second week of life. Postmortem hippocampal tissue was obtained on postnatal days 29, 64, and 90 and processed for glial fibrillary acidic protein (GFAP), NeuN, and calbindin expression. The data revealed no significant changes on postnatal day (PND) 29 but a significant increase in hilar NeuN-positive cells in some regions on PND 64 and 90 that were identified as ectopic granule cells. Further, an increase in GFAP positive cell counts and evidence of reactive astrogliosis was found on PND 90 but not at earlier time points. We conclude that changes in cellular expression, possibly due to on-going non-convulsive seizures, develop slowly in this model and may contribute to progressive brain dysfunction that culminates in a seizure-prone phenotype.

AB - Epilepsies affect about 4% of the population and are frequently characterized by a prolonged "silent" period before the onset of spontaneous seizures. Most current animal models of epilepsy either involve acute seizure induction or kindling protocols that induce repetitive seizures. We have developed a rat model of epilepsy that is characterized by a slowly progressing series of behavioral abnormalities prior to the onset of behavioral seizures. In the current study, we further describe an accompanying progression of cytoarchitectural changes in the hippocampal formation. Groups of male and female SD rats received serial injections of a low dose of domoic acid (0.020 mg/kg) (or vehicle) throughout the second week of life. Postmortem hippocampal tissue was obtained on postnatal days 29, 64, and 90 and processed for glial fibrillary acidic protein (GFAP), NeuN, and calbindin expression. The data revealed no significant changes on postnatal day (PND) 29 but a significant increase in hilar NeuN-positive cells in some regions on PND 64 and 90 that were identified as ectopic granule cells. Further, an increase in GFAP positive cell counts and evidence of reactive astrogliosis was found on PND 90 but not at earlier time points. We conclude that changes in cellular expression, possibly due to on-going non-convulsive seizures, develop slowly in this model and may contribute to progressive brain dysfunction that culminates in a seizure-prone phenotype.

KW - Journal Article

U2 - 10.1007/s13167-017-0111-9

DO - 10.1007/s13167-017-0111-9

M3 - Journal article

C2 - 29021835

VL - 8

SP - 247

EP - 254

JO - The EPMA journal

JF - The EPMA journal

SN - 1878-5077

IS - 3

ER -