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Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics.

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Title: Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics.
Authors: Lucchi, Chiara (AUTHOR), Costa, Anna Maria (AUTHOR), Senn, Lara (AUTHOR), Messina, Simone (AUTHOR), Rustichelli, Cecilia (AUTHOR), Biagini, Giuseppe (AUTHOR)
Source: Epilepsia (Series 4). Sep2020, Vol. 61 Issue 9, pe129-e134. 6p.
Subjects: Status epilepticus, Tandem mass spectrometry, Kainic acid, Cerebrospinal fluid, Neurotransmitters, Translocator proteins
Abstract: Neurosteroids can modulate γ‐aminobutyric acid type A receptor‐mediated inhibitory currents. Recently, we discovered that the neurosteroids progesterone, 5α‐dihydroprogesterone, allopregnanolone, and pregnanolone are reduced in the cerebrospinal fluid of patients with status epilepticus (SE). However, it is undetermined whether neurosteroids influence SE. For this reason, first we evaluated whether the inhibitor of adrenocortical steroid production trilostane (50 mg/kg) could modify the levels of neurosteroids in the hippocampus and neocortex, and we found a remarkable increase in pregnenolone, progesterone, 5α‐dihydroprogesterone, and allopregnanolone levels using liquid chromatography tandem mass spectrometry. Second, we characterized the dynamics of SE in the presence of the varied neurosteroidal milieu by a single intraperitoneal kainic acid (KA; 15 mg/kg) injection in trilostane‐treated rats and their controls. Convulsions started in advance in the trilostane group, already appearing 90 minutes after the KA injection. In contrast to controls, convulsions prevalently developed as generalized seizures with loss of posture in the trilostane group. However, this effect was transient, and convulsions waned 2 hours before the control group. Moreover, electrocorticographic traces of convulsions were shorter in trilostane‐treated rats, especially at the 180‐minute (P <.001) and 210‐minute (P <.01) time points. These findings indicate that endogenous neurosteroids remarkably modulate SE dynamics. [ABSTRACT FROM AUTHOR]
Copyright of Epilepsia (Series 4) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics.
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  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Lucchi%2C+Chiara%22&quot;&gt;Lucchi, Chiara&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Costa%2C+Anna+Maria%22&quot;&gt;Costa, Anna Maria&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Senn%2C+Lara%22&quot;&gt;Senn, Lara&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Messina%2C+Simone%22&quot;&gt;Messina, Simone&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Rustichelli%2C+Cecilia%22&quot;&gt;Rustichelli, Cecilia&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Biagini%2C+Giuseppe%22&quot;&gt;Biagini, Giuseppe&lt;/searchLink&gt; (AUTHOR)
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22Epilepsia+%28Series+4%29%22&quot;&gt;Epilepsia (Series 4)&lt;/searchLink&gt;. Sep2020, Vol. 61 Issue 9, pe129-e134. 6p.
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  Data: &lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Status+epilepticus%22&quot;&gt;Status epilepticus&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Tandem+mass+spectrometry%22&quot;&gt;Tandem mass spectrometry&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Kainic+acid%22&quot;&gt;Kainic acid&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Cerebrospinal+fluid%22&quot;&gt;Cerebrospinal fluid&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Neurotransmitters%22&quot;&gt;Neurotransmitters&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Translocator+proteins%22&quot;&gt;Translocator proteins&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract
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  Data: Neurosteroids can modulate γ‐aminobutyric acid type A receptor‐mediated inhibitory currents. Recently, we discovered that the neurosteroids progesterone, 5α‐dihydroprogesterone, allopregnanolone, and pregnanolone are reduced in the cerebrospinal fluid of patients with status epilepticus (SE). However, it is undetermined whether neurosteroids influence SE. For this reason, first we evaluated whether the inhibitor of adrenocortical steroid production trilostane (50 mg/kg) could modify the levels of neurosteroids in the hippocampus and neocortex, and we found a remarkable increase in pregnenolone, progesterone, 5α‐dihydroprogesterone, and allopregnanolone levels using liquid chromatography tandem mass spectrometry. Second, we characterized the dynamics of SE in the presence of the varied neurosteroidal milieu by a single intraperitoneal kainic acid (KA; 15 mg/kg) injection in trilostane‐treated rats and their controls. Convulsions started in advance in the trilostane group, already appearing 90 minutes after the KA injection. In contrast to controls, convulsions prevalently developed as generalized seizures with loss of posture in the trilostane group. However, this effect was transient, and convulsions waned 2 hours before the control group. Moreover, electrocorticographic traces of convulsions were shorter in trilostane‐treated rats, especially at the 180‐minute (P &lt;.001) and 210‐minute (P &lt;.01) time points. These findings indicate that endogenous neurosteroids remarkably modulate SE dynamics. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: &lt;i&gt;Copyright of Epilepsia (Series 4) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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    Identifiers:
      – Type: doi
        Value: 10.1111/epi.16654
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 6
        StartPage: e129
    Subjects:
      – SubjectFull: Status epilepticus
        Type: general
      – SubjectFull: Tandem mass spectrometry
        Type: general
      – SubjectFull: Kainic acid
        Type: general
      – SubjectFull: Cerebrospinal fluid
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      – SubjectFull: Neurotransmitters
        Type: general
      – SubjectFull: Translocator proteins
        Type: general
    Titles:
      – TitleFull: Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics.
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            NameFull: Lucchi, Chiara
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            NameFull: Costa, Anna Maria
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              M: 09
              Text: Sep2020
              Type: published
              Y: 2020
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              Value: 61
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