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Nonconvulsive status epilepticus in rats leads to brain pathology

Avdic, Una LU ; Ahl, Matilda LU ; Chugh, Deepti LU ; Ali, Idrish LU ; Chary, Karthik; Sierra, Alejandra and Ekdahl, Christine T. LU (2018) In Epilepsia 59(5). p.945-958
Abstract

Objective: Status epilepticus (SE) is an abnormally prolonged epileptic seizure that if associated with convulsive motor symptoms is potentially life threatening for a patient. However, 20%-40% of patients with SE lack convulsive events and instead present with more subtle semiology such as altered consciousness and less motor activity. Today, there is no general consensus regarding to what extent nonconvulsive SE (NCSE) is harmful to the brain, which adds uncertainty to stringent treatment regimes. Methods: Here, we evaluated brain pathology in an experimental rat and mouse model of complex partial NCSE originating in the temporal lobes with Western blot analysis, immunohistochemistry, and ex vivo diffusion tensor imaging (DTI). The... (More)

Objective: Status epilepticus (SE) is an abnormally prolonged epileptic seizure that if associated with convulsive motor symptoms is potentially life threatening for a patient. However, 20%-40% of patients with SE lack convulsive events and instead present with more subtle semiology such as altered consciousness and less motor activity. Today, there is no general consensus regarding to what extent nonconvulsive SE (NCSE) is harmful to the brain, which adds uncertainty to stringent treatment regimes. Methods: Here, we evaluated brain pathology in an experimental rat and mouse model of complex partial NCSE originating in the temporal lobes with Western blot analysis, immunohistochemistry, and ex vivo diffusion tensor imaging (DTI). The NCSE was induced by electrical stimulation with intrahippocampal electrodes and terminated with pentobarbital anesthesia. Video-electroencephalographic recordings were performed throughout the experiment. Results: DTI of mice 7 weeks post-NCSE showed no robust long-lasting changes in fractional anisotropy within the hippocampal epileptic focus. Instead, we found pathophysiological changes developing over time when measuring protein levels and cell counts in extracted brain tissue. At 6 and 24 hours post-NCSE in rats, few changes were observed within the hippocampus and cortical or subcortical structures in Western blot analyses of key components of the cellular immune response and synaptic protein expression, while neurodegeneration had started. However, 1 week post-NCSE, both excitatory and inhibitory synaptic protein levels were decreased in hippocampus, concomitant with an excessive microglial and astrocytic activation. At 4 weeks, a continuous immune response in the hippocampus was accompanied with neuronal loss. Levels of the excitatory synaptic adhesion molecule N-cadherin were decreased specifically in rats that developed unprovoked spontaneous seizures (epileptogenesis) within 1 month following NCSE, compared to rats only exhibiting acute symptomatic seizures within 1 week post-NCSE. Significance: These findings provide evidence for a significant brain pathology following NCSE in an experimental rodent model.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diffusion tensor imaging, Inflammation, N-cadherin, Nonconvulsive status epilepticus, Synaptic proteins
in
Epilepsia
volume
59
issue
5
pages
945 - 958
publisher
Wiley-Blackwell
external identifiers
  • scopus:85045210260
ISSN
0013-9580
DOI
10.1111/epi.14070
language
English
LU publication?
yes
id
ef01faf4-a657-454e-b2c5-7af9246162df
date added to LUP
2018-04-23 10:29:03
date last changed
2019-03-19 03:53:25
@article{ef01faf4-a657-454e-b2c5-7af9246162df,
  abstract     = {<p>Objective: Status epilepticus (SE) is an abnormally prolonged epileptic seizure that if associated with convulsive motor symptoms is potentially life threatening for a patient. However, 20%-40% of patients with SE lack convulsive events and instead present with more subtle semiology such as altered consciousness and less motor activity. Today, there is no general consensus regarding to what extent nonconvulsive SE (NCSE) is harmful to the brain, which adds uncertainty to stringent treatment regimes. Methods: Here, we evaluated brain pathology in an experimental rat and mouse model of complex partial NCSE originating in the temporal lobes with Western blot analysis, immunohistochemistry, and ex vivo diffusion tensor imaging (DTI). The NCSE was induced by electrical stimulation with intrahippocampal electrodes and terminated with pentobarbital anesthesia. Video-electroencephalographic recordings were performed throughout the experiment. Results: DTI of mice 7 weeks post-NCSE showed no robust long-lasting changes in fractional anisotropy within the hippocampal epileptic focus. Instead, we found pathophysiological changes developing over time when measuring protein levels and cell counts in extracted brain tissue. At 6 and 24 hours post-NCSE in rats, few changes were observed within the hippocampus and cortical or subcortical structures in Western blot analyses of key components of the cellular immune response and synaptic protein expression, while neurodegeneration had started. However, 1 week post-NCSE, both excitatory and inhibitory synaptic protein levels were decreased in hippocampus, concomitant with an excessive microglial and astrocytic activation. At 4 weeks, a continuous immune response in the hippocampus was accompanied with neuronal loss. Levels of the excitatory synaptic adhesion molecule N-cadherin were decreased specifically in rats that developed unprovoked spontaneous seizures (epileptogenesis) within 1 month following NCSE, compared to rats only exhibiting acute symptomatic seizures within 1 week post-NCSE. Significance: These findings provide evidence for a significant brain pathology following NCSE in an experimental rodent model.</p>},
  author       = {Avdic, Una and Ahl, Matilda and Chugh, Deepti and Ali, Idrish and Chary, Karthik and Sierra, Alejandra and Ekdahl, Christine T.},
  issn         = {0013-9580},
  keyword      = {Diffusion tensor imaging,Inflammation,N-cadherin,Nonconvulsive status epilepticus,Synaptic proteins},
  language     = {eng},
  month        = {04},
  number       = {5},
  pages        = {945--958},
  publisher    = {Wiley-Blackwell},
  series       = {Epilepsia},
  title        = {Nonconvulsive status epilepticus in rats leads to brain pathology},
  url          = {http://dx.doi.org/10.1111/epi.14070},
  volume       = {59},
  year         = {2018},
}