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Characteristics of Epileptiform Spike-wave Discharges and Chronic Histopathology in Controlled Cortical Impact Model of Sprague–Dawley Rats

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Abstract

Post-traumatic epilepsy (PTE) is a serious complication that can occur following traumatic brain injury (TBI). Sustained secondary changes after TBI promote the process of PTE. Here, we aim to evaluate changes in behavior, electrocorticogram, and histomorphology in rats following chronic TBI models. We observed intensive 7–8 Hz spike-wave-discharges (SWDs) at frontal recording sites and quantified them in SD rats with different degrees of TBI and compared them with age-matched sham rats to evaluate the association between SWDs and injury severity. Notably, although SWDs were even presented in the sham group, the number and duration of events were much lower than those in the TBI groups. SWDs have numerous similarities to absence seizures, such as abrupt onset, termination, and lack of postictal suppression, which may be the nonconvulsive characteristics of PTE. Retigabine, a novel antiepileptic drug, is ineffective in reducing SWDs. In addition, we examined chronic histopathological changes in TBI rats. Rats subjected to moderate and severe TBI exhibited significantly impaired neurological function, which was accompanied by marked cortical injury, hippocampus deformation, reactive gliosis, and mossy fiber sprouting. Long-term progressive structural changes in the brain are one of the characteristics of epileptogenesis after TBI. Our study provided the potential value of epileptiform SWDs in reflecting the nonconvulsive characteristic of PTE and highlighted the vital role of chronic pathological changes, such as reactive gliosis, in promoting the epileptogenesis following TBI.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

TBI:

Traumatic brain injury

PTE:

Post-traumatic epilepsy

CCI:

Controlled cortical impact

DG:

Dentate gyrus

ASs:

Absence seizures

SWDs:

Spike-wave-discharges

ECoG:

Electrocorticogram

GAERS:

Genetic Absence Epilepsy Rats from Strasbourg

WAG/Rij:

Wistar Albino Glaxo Rats from Rijswijk

AP:

Anteroposterior

ML:

Mediolateral

mNSS:

Modified Neurological Severity Score

PFA:

Paraformaldehyde

Iba1:

Ionized calcium binding adaptor molecule 1

GFAP:

Glial fibrillary acidic protein

MFS:

Mossy fiber sprouting

ZnT3:

Zinc transporter 3

FPI:

Fluid percussion injury

GABA:

Gamma-aminobutyric acid

eGABAAR:

Extrasynaptic GABAA receptors

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Acknowledgements

We thank Sarina Iwabuchi, PhD, from Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing a draft of this manuscript.

Funding

This work was mainly supported by the startup fund from Capital Medical University Advanced Innovation Center for Human Brain Protection (20181101, JW), and partially by grants from National Key R&D Program of China (2017YFC1307501, QW), Beijing-Tianjin-Hebei Cooperative Basic Research Program (H2018206435, QW), the National Natural Science Foundation of China (81870935, JW).

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Author notes

  1. Lei Sun and Ru Liu have contributed equally to this work.

Authors and Affiliations

  1. Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China

    Lei Sun, Ru Liu, Tingting Yu, Jianping Wu & Qun Wang

  2. Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100070, China

    Lei Sun, Ru Liu, Huajun Yang, Tingting Yu & Jianping Wu

  3. China National Clinical Research Center for Neurological Diseases, Beijing, 100070, China

    Lei Sun, Ru Liu, Tingting Yu, Jianping Wu & Qun Wang

  4. School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China

    Jianping Wu

  5. Beijing Institute for Brain Disorders, Beijing, 100069, China

    Qun Wang

  6. Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Huajun Yang

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Contributions

LS and RL conducted literature review and wrote the initial draft of the manuscript. HY and TYmade preliminary revision. JW and QW made critical revision. All authors contributed to manuscript revision and approved the submitted version.

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Correspondence to Jianping Wu or Qun Wang.

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All procedures were approved by the Animal Care and Use Committee of Capital Medical University (Beijing, China).

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Sun, L., Liu, R., Yang, H. et al. Characteristics of Epileptiform Spike-wave Discharges and Chronic Histopathology in Controlled Cortical Impact Model of Sprague–Dawley Rats. Neurochem Res 47, 3615–3626 (2022). https://doi.org/10.1007/s11064-022-03542-y

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