Circumscribing Femtosecond Laser Cuts in Cortical Layers II-IV Attenuate Seizure Propagation Without Behavioral Impact in a Mouse Model of Focal Epilepsy
Abstract number :
1.088
Submission category :
2. Translational Research / 2B. Devices, Technologies, Stem Cells
Year :
2021
Submission ID :
1826507
Source :
www.aesnet.org
Presentation date :
12/4/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:54 AM
Authors :
Seth Lieberman, BS - Cornell University; Daniel Rivera - Meinig School of Biomedical Engineering - Cornell University; Ryan Morton - Meinig School of Biomedical Engineering - Cornell University; Amrit Hingorani - Meinig School of Biomedical Engineering - Cornell University; Teresa Southard - College of Veterinary Medicine - Cornell University; Lynn Johnson - Statistical Consulting Unit - Cornell University; Jennifer Reufauf - Meinig School of Biomedical Engineering - Cornell University; Ryan Radwanski - Meinig School of Biomedical Engineering - Cornell University; Mingrui Zhao - Department of Neurological Surgery - Weill Cornell Medical School; Oliver Bracko - Meinig School of Biomedical Engineering - Cornell University; Theodore Schwartz - Department of Neurological Surgery - Weill Cornell Medical School; Chris Schaffer - Meinig School of Biomedical Engineering - Cornell University
Rationale: Epilepsy affects about 50 million people worldwide. Focal epilepsy is characterized by seizures that initiate in one part of the brain and propagate out to other regions. Unfortunately, about 45% of patients with focal epilepsy become refractory to all medication and the only alternative is invasive neurosurgical approaches that often leave patients with significant neurologic deficits. Research utilizing in vivo imaging has shown that acutely induced seizures mainly propagate through lateral connections in layers II/III of the cortex. Severing these connections to reduce seizure spread was proposed many years ago. Unfortunately, the technology did not exist to sever these sub-surface lateral connections without causing excessive damage to the surface vasculature or the rest of the brain. However, with the advent of a new laser scalpel technique using tightly-focused femtosecond infrared laser pulses we were able to make micrometer-scale, sub-surface incisions without damaging the surrounding tissue.
Methods: In this study we tested the long-term efficacy of laser cuts in layers II-IV surrounding a chronic neocortical seizure focus as well as determining the effect these cuts have on neuronal structure and function. Epileptiform activity was induced through a microinjection of iron chloride.
Results: In mice without laser cuts over 85% of seizures propagated across the cortex while in mice with laser cuts only 5% of seizures propagated. Chronic multi-exposure laser speckle imaging of ablated regions showed only a minor reduction of blood flow to the circumscribed region and histology after a month indicated healthy neurons with only a mild gliosis and scaring at the cut. When laser cuts were localizing the to forelimb motor cortex, we found only a minor acute deficit on a complex reaching task that quickly improved.
Conclusions: Ultimately, this new neurosurgical approach was able to significantly block seizure propagation while minimally affecting both the structure and function of surrounding brain tissue suggesting that this new approach could provide a more minimally invasive and effective solution for people with focal epilepsy.
Funding: Please list any funding that was received in support of this abstract.: Financial support from NIH, grant number MH119880.
Translational Research