Neuroprotective effects of estrogens on hippocampal cells in adult female rats after status epilepticus

Jana Velíšková, Libor Velíšek, Aristea S. Galanopoulou, Ellen F. Sperber

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

Purpose: Estrogens have neuroprotective effects in ischemia, stroke, and other conditions leading to neuronal cell death (e.g., Alzheimer's disease). The present study examined whether estrogens may have neuroprotective effects after seizures. Methods: The kainic acid model was used to determine if estrogens protect hippocampal cells after status epilepticus in adult female rats. Rats were ovariectomized 1 week before hormone replacement. β-Estradiol benzoate (EB; 2 μg in 0.1 mL of oil) was injected subcutaneously 48 and 24 hours before seizure testing. We administered kainic acid (16 mg/kg intraperitoneally) and behaviorally monitored the rats for 5 hours. After this time, all rats were injected with pentobarbital (50 mg/kg intraperitoneally) irrespective of seizure severity. Some rats received two additional doses of EB, one immediately and one 24 hours after the seizures. Another group of rats received only these two doses of EB after the seizures, and yet another group of rats received pretreatment with the intracellular EB receptor antagonist tamoxifen before each of four EB injections. Control rats received oil instead of EB. Rats were killed 48 hours after seizures. Neuronal damage was evaluated in silver-impregnated and Nissl-stained sections. Results: Estrogen treatment before kalnic acid administration significantly delayed the onset of kainic acid-induced clonic seizures, whereas it did not change the onset of status epilepticus compared with oil-treated controls. Furthermore, estrogen treatment significantly protected against kainic acid-induced seizure-related mortality. In control rats, examination of Nissl-stained and silver-impregnated slides revealed severe neuronal damage in the vulnerable pyramidal neurons of the hippocampal CA3 subfield and in the hilus of the dentate gyrus. Estrogen pretreatment, as well as the combination of pretreatment and posttreatment, significantly reduced the number of argyrophilic neurons in both the CA3 and the dentate gyrus. Posttreatment only had no protective effects. The data indicate that intracellular EB receptors mediate this type of neuroprotective effect, because the tamoxifen pretreatment abolished EB neuroprotection. Conclusions: Our results suggest that estrogens can be benefical in protecting against status epilepticus-induced hippocampal damage. Hormonal conditions may have differential effects on underlying epileptic state in some patients. Therefore, more studies are necessary to determine the prospective therapeutic advantage of hormonal treatment in seizure-related damage.

Original languageEnglish (US)
JournalEpilepsia
Volume41
Issue numberSUPPL. 6
StatePublished - 2000

Fingerprint

Status Epilepticus
Neuroprotective Agents
Estrogens
Seizures
Kainic Acid
Oils
Dentate Gyrus
Tamoxifen
Silver
Pyramidal Cells
Pentobarbital
Therapeutics
Alzheimer Disease
Cell Death
Ischemia
Stroke
Hormones
Neurons
Injections
Acids

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Neuroprotective effects of estrogens on hippocampal cells in adult female rats after status epilepticus. / Velíšková, Jana; Velíšek, Libor; Galanopoulou, Aristea S.; Sperber, Ellen F.

In: Epilepsia, Vol. 41, No. SUPPL. 6, 2000.

Research output: Contribution to journalArticle

Velíšková, Jana ; Velíšek, Libor ; Galanopoulou, Aristea S. ; Sperber, Ellen F. / Neuroprotective effects of estrogens on hippocampal cells in adult female rats after status epilepticus. In: Epilepsia. 2000 ; Vol. 41, No. SUPPL. 6.
@article{1df67b942ec74206aab939ea68edf5ac,
title = "Neuroprotective effects of estrogens on hippocampal cells in adult female rats after status epilepticus",
abstract = "Purpose: Estrogens have neuroprotective effects in ischemia, stroke, and other conditions leading to neuronal cell death (e.g., Alzheimer's disease). The present study examined whether estrogens may have neuroprotective effects after seizures. Methods: The kainic acid model was used to determine if estrogens protect hippocampal cells after status epilepticus in adult female rats. Rats were ovariectomized 1 week before hormone replacement. β-Estradiol benzoate (EB; 2 μg in 0.1 mL of oil) was injected subcutaneously 48 and 24 hours before seizure testing. We administered kainic acid (16 mg/kg intraperitoneally) and behaviorally monitored the rats for 5 hours. After this time, all rats were injected with pentobarbital (50 mg/kg intraperitoneally) irrespective of seizure severity. Some rats received two additional doses of EB, one immediately and one 24 hours after the seizures. Another group of rats received only these two doses of EB after the seizures, and yet another group of rats received pretreatment with the intracellular EB receptor antagonist tamoxifen before each of four EB injections. Control rats received oil instead of EB. Rats were killed 48 hours after seizures. Neuronal damage was evaluated in silver-impregnated and Nissl-stained sections. Results: Estrogen treatment before kalnic acid administration significantly delayed the onset of kainic acid-induced clonic seizures, whereas it did not change the onset of status epilepticus compared with oil-treated controls. Furthermore, estrogen treatment significantly protected against kainic acid-induced seizure-related mortality. In control rats, examination of Nissl-stained and silver-impregnated slides revealed severe neuronal damage in the vulnerable pyramidal neurons of the hippocampal CA3 subfield and in the hilus of the dentate gyrus. Estrogen pretreatment, as well as the combination of pretreatment and posttreatment, significantly reduced the number of argyrophilic neurons in both the CA3 and the dentate gyrus. Posttreatment only had no protective effects. The data indicate that intracellular EB receptors mediate this type of neuroprotective effect, because the tamoxifen pretreatment abolished EB neuroprotection. Conclusions: Our results suggest that estrogens can be benefical in protecting against status epilepticus-induced hippocampal damage. Hormonal conditions may have differential effects on underlying epileptic state in some patients. Therefore, more studies are necessary to determine the prospective therapeutic advantage of hormonal treatment in seizure-related damage.",
author = "Jana Vel{\'i}škov{\'a} and Libor Vel{\'i}šek and Galanopoulou, {Aristea S.} and Sperber, {Ellen F.}",
year = "2000",
language = "English (US)",
volume = "41",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "SUPPL. 6",

}

TY - JOUR

T1 - Neuroprotective effects of estrogens on hippocampal cells in adult female rats after status epilepticus

AU - Velíšková, Jana

AU - Velíšek, Libor

AU - Galanopoulou, Aristea S.

AU - Sperber, Ellen F.

PY - 2000

Y1 - 2000

N2 - Purpose: Estrogens have neuroprotective effects in ischemia, stroke, and other conditions leading to neuronal cell death (e.g., Alzheimer's disease). The present study examined whether estrogens may have neuroprotective effects after seizures. Methods: The kainic acid model was used to determine if estrogens protect hippocampal cells after status epilepticus in adult female rats. Rats were ovariectomized 1 week before hormone replacement. β-Estradiol benzoate (EB; 2 μg in 0.1 mL of oil) was injected subcutaneously 48 and 24 hours before seizure testing. We administered kainic acid (16 mg/kg intraperitoneally) and behaviorally monitored the rats for 5 hours. After this time, all rats were injected with pentobarbital (50 mg/kg intraperitoneally) irrespective of seizure severity. Some rats received two additional doses of EB, one immediately and one 24 hours after the seizures. Another group of rats received only these two doses of EB after the seizures, and yet another group of rats received pretreatment with the intracellular EB receptor antagonist tamoxifen before each of four EB injections. Control rats received oil instead of EB. Rats were killed 48 hours after seizures. Neuronal damage was evaluated in silver-impregnated and Nissl-stained sections. Results: Estrogen treatment before kalnic acid administration significantly delayed the onset of kainic acid-induced clonic seizures, whereas it did not change the onset of status epilepticus compared with oil-treated controls. Furthermore, estrogen treatment significantly protected against kainic acid-induced seizure-related mortality. In control rats, examination of Nissl-stained and silver-impregnated slides revealed severe neuronal damage in the vulnerable pyramidal neurons of the hippocampal CA3 subfield and in the hilus of the dentate gyrus. Estrogen pretreatment, as well as the combination of pretreatment and posttreatment, significantly reduced the number of argyrophilic neurons in both the CA3 and the dentate gyrus. Posttreatment only had no protective effects. The data indicate that intracellular EB receptors mediate this type of neuroprotective effect, because the tamoxifen pretreatment abolished EB neuroprotection. Conclusions: Our results suggest that estrogens can be benefical in protecting against status epilepticus-induced hippocampal damage. Hormonal conditions may have differential effects on underlying epileptic state in some patients. Therefore, more studies are necessary to determine the prospective therapeutic advantage of hormonal treatment in seizure-related damage.

AB - Purpose: Estrogens have neuroprotective effects in ischemia, stroke, and other conditions leading to neuronal cell death (e.g., Alzheimer's disease). The present study examined whether estrogens may have neuroprotective effects after seizures. Methods: The kainic acid model was used to determine if estrogens protect hippocampal cells after status epilepticus in adult female rats. Rats were ovariectomized 1 week before hormone replacement. β-Estradiol benzoate (EB; 2 μg in 0.1 mL of oil) was injected subcutaneously 48 and 24 hours before seizure testing. We administered kainic acid (16 mg/kg intraperitoneally) and behaviorally monitored the rats for 5 hours. After this time, all rats were injected with pentobarbital (50 mg/kg intraperitoneally) irrespective of seizure severity. Some rats received two additional doses of EB, one immediately and one 24 hours after the seizures. Another group of rats received only these two doses of EB after the seizures, and yet another group of rats received pretreatment with the intracellular EB receptor antagonist tamoxifen before each of four EB injections. Control rats received oil instead of EB. Rats were killed 48 hours after seizures. Neuronal damage was evaluated in silver-impregnated and Nissl-stained sections. Results: Estrogen treatment before kalnic acid administration significantly delayed the onset of kainic acid-induced clonic seizures, whereas it did not change the onset of status epilepticus compared with oil-treated controls. Furthermore, estrogen treatment significantly protected against kainic acid-induced seizure-related mortality. In control rats, examination of Nissl-stained and silver-impregnated slides revealed severe neuronal damage in the vulnerable pyramidal neurons of the hippocampal CA3 subfield and in the hilus of the dentate gyrus. Estrogen pretreatment, as well as the combination of pretreatment and posttreatment, significantly reduced the number of argyrophilic neurons in both the CA3 and the dentate gyrus. Posttreatment only had no protective effects. The data indicate that intracellular EB receptors mediate this type of neuroprotective effect, because the tamoxifen pretreatment abolished EB neuroprotection. Conclusions: Our results suggest that estrogens can be benefical in protecting against status epilepticus-induced hippocampal damage. Hormonal conditions may have differential effects on underlying epileptic state in some patients. Therefore, more studies are necessary to determine the prospective therapeutic advantage of hormonal treatment in seizure-related damage.

UR - http://www.scopus.com/inward/record.url?scp=0033816050&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033816050&partnerID=8YFLogxK

M3 - Article

C2 - 10999516

AN - SCOPUS:0033816050

VL - 41

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - SUPPL. 6

ER -