Circumscribing Laser Cuts Attenuate Seizure Propagation in a Mouse Model of Focal Epilepsy.

Seth Lieberman, Daniel A Rivera, Ryan Morton, Amrit Hingorani, Teresa L Southard, Lynn Johnson, Jennifer Reukauf, Ryan E Radwanski, Mingrui Zhao, Nozomi Nishimura, Oliver Bracko, Theodore H Schwartz, Chris B Schaffer
Author Information
  1. Seth Lieberman: Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.
  2. Daniel A Rivera: Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.
  3. Ryan Morton: Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.
  4. Amrit Hingorani: Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.
  5. Teresa L Southard: College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
  6. Lynn Johnson: Statistical Consulting Unit, Cornell University, Ithaca, NY, 14853, USA.
  7. Jennifer Reukauf: Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.
  8. Ryan E Radwanski: Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.
  9. Mingrui Zhao: Department of Neurological Surgery, Weill Cornell Medicine of Cornell University, New York, NY, 10065, USA.
  10. Nozomi Nishimura: Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.
  11. Oliver Bracko: Department of Biology, The University of Miami, Coral Gables, FL, 33134, USA.
  12. Theodore H Schwartz: Department of Neurological Surgery, Weill Cornell Medicine of Cornell University, New York, NY, 10065, USA.
  13. Chris B Schaffer: Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA. ORCID

Abstract

In partial onset epilepsy, seizures arise focally in the brain and often propagate. Patients frequently become refractory to medical management, leaving neurosurgery, which can cause neurologic deficits, as a primary treatment. In the cortex, focal seizures spread through horizontal connections in layers II/III, suggesting that severing these connections can block seizures while preserving function. Focal neocortical epilepsy is induced in mice, sub-surface cuts are created surrounding the seizure focus using tightly-focused femtosecond laser pulses, and electrophysiological recordings are acquired at multiple locations for 3-12 months. Cuts reduced seizure frequency in most animals by 87%, and only 5% of remaining seizures propagated to the distant electrodes, compared to 80% in control animals. These cuts produced a modest decrease in cortical blood flow that recovered and left a ≈20-µm wide scar with minimal collateral damage. When placed over the motor cortex, cuts do not cause notable deficits in a skilled reaching task, suggesting they hold promise as a novel neurosurgical approach for intractable focal cortical epilepsy.

Keywords

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Grants

  1. UL1 RR024996/NCRR NIH HHS
  2. R43 MH119880/NIMH NIH HHS
  3. AG066001/NIA NIH HHS
  4. /Cornell University, Ithaca-WCMC seed grant
  5. R21 AG066001/NIA NIH HHS
  6. NS078644/NINDS NIH HHS
  7. MH119880/National Institute of Mental Health and Neurosciences
  8. /Daedalus Fund for Innovation
  9. R21 NS078644/NINDS NIH HHS

MeSH Term

Animals
Mice
Disease Models, Animal
Epilepsies, Partial
Seizures
Male
Mice, Inbred C57BL
Laser Therapy
Electroencephalography

Word Cloud

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