Biology subjects

Costine-Bartell, B. A.

Publications and source records attributed to Costine-Bartell, B. A..

3 recordsLinked to original sources

bioRxiv2023

Brief Apnea and Hypoventilation Reduces Seizure Duration and Shifts Seizure Location for Several Hours in a Model of Severe Traumatic Brain Injury.

ObjectiveSeizures are difficult to control in infants and toddlers. Seizures with periods of apnea and hypoventilation are common following severe traumatic brain injury (TBI). In our multifactorial, severe TBI model (cortical impact, mass effect, subdural hematoma, subarachnoid hemorrhage, seizures induced with kainic acid, and brief apnea and hypoventilation), we observed that brief apnea with hypoventilation (A&H) after induced seizure acutely interrupted seizures, leading us to hypothesize that brief A&H might reduce seizure duration beyond the brief hypoxia and hypercapnia for several hours thereafter. The effects of the timing of A&H on seizure duration and location might inform the pathophysiology of this hypoxic-ischemic injury as well as potential treatments. MethodsPiglets (1 week or 1 month old) received multi-factorial injuries. Apnea and hypoventilation (1 min apnea, 10 min hypoventilation; A&H) was induced either before or after seizure induction, or as a control piglets received subdural/subarachnoid hematoma and seizure without A&H. In an intensive care unit, piglets were sedated, intubated, mechanically ventilated, and epidural EEG was recorded for an average of 18 hours after seizure induction. ResultsIn our severe TBI model, A&H after seizure reduced ipsilateral seizure burden by 80% compared to the same injuries without A&H. In the A&H before seizure induction group, more piglets had exclusively contralateral seizures though most piglets in all groups had seizures that shifted location throughout the several hours of seizure. After 8-10 hours, seizures transitioned to interictal epileptiform discharges regardless of timing of A&H. SignificanceEven brief A&H may alter traumatic seizures We will address the possibility of induced spreading depolarization prior to preclinical investigations of hypercapnia with normoxia, with controlled intracranial pressure, as a therapeutic option for children with status epilepticus after hemorrhagic TBI.

neuroscience↗

bioRxiv2023

2-photon imaging of fluorescent proteins in living swine

A common point of failure in translation of preclinical neurological research to successful clinical trials comes in the giant leap from rodent models to humans. Non-human primates are phylogenetically close to humans, but cost and ethical considerations prohibit their widespread usage in preclinical trials. Swine have large, gyrencencephalic brains, which are biofidelic to human brains. Their classification as livestock makes them a readily accessible model organism. However, their size has precluded experiments involving intravital imaging with cellular resolution. Here, we present a suite of techniques and tools for in vivo imaging of porcine brains with subcellular resolution. Specifically, we describe surgical techniques for implanting a synthetic, flexible, transparent dural window for chronic optical access to the neocortex. We detail optimized parameters and methods for injecting adeno-associated virus vectors through the cranial imaging window to express fluorescent proteins. We introduce a large-animal 2-photon microscope that was constructed with off-the shelf components, has a gantry design capable of accommodating animals > 80 kg, and is equipped with a high-speed digitizer for digital fluorescence lifetime imaging. Finally, we delineate strategies developed to mitigate the substantial motion artifact that complicates high resolution imaging in large animals, including heartbeat-triggered high-speed image stack acquisition. The effectiveness of this approach is demonstrated in sample images acquired from pigs transduced with the chloride-sensitive fluorescent protein SuperClomeleon.

neuroscience↗

bioRxiv2022

Robust, long-term video EEG monitoring in a porcine model of post-traumatic epilepsy.

To date, post-traumatic epilepsy (PTE) research in large animal models has been limited. Recent advances in neocortical microscopy have made possible new insights into neocortical PTE. However, it is very difficult to engender convincing neocortical PTE in rodents. Thus, large animal models that develop neocortical PTE may provide useful insights that also can be more comparable to human patients. Because gyrencephalic species have prolonged latent periods, long-term video EEG recording is required. Here, we report a fully subcutaneous EEG implant with synchronized video in freely ambulatory swine for up to 14 months during epileptogenesis following bilateral cortical impact injuries or sham surgery The advantages of this system include the availability of a commercially available system that is simple to install, a low failure rate after surgery for EEG implantation, radiotelemetry that enables continuous monitoring of freely ambulating animals, excellent synchronization to video to EEG, and a robust signal to noise ratio. The disadvantages of this system in this species and age are the accretion of skull bone which entirely embedded a subset of skull screws and EEG electrodes, and the inability to rearrange the EEG electrode array. These disadvantages may be overcome by splicing a subdural electrode strip to the electrode leads so that skull growth is less likely to interfere with long-term signal capture and by placing two implants for a more extensive montage. This commercially available system in this bilateral cortical impact swine model may be useful to a wide range of investigators studying epileptogenesis in PTE. SignificancePost-traumatic epilepsy (PTE) is a cause of significant morbidity after traumatic brain injury (TBI) and is often drug-resistant. Robust, informative animal models would greatly facilitate PTE research. Ideally, this biofidelic model of PTE would utilize a species that approximates human brain anatomy, brain size, glial populations, and inflammatory pathways. An ideal model would also incorporate feasible methods for long-term video EEG recording required to quantify seizure activity. Here, we describe the first model of PTE in swine and describe a method for robust long-term video EEG monitoring for up to 14 months post-TBI. The relatively easy "out-of-the-box" radiotelemetry system and surgical techniques described here will be adaptable by a wide array of investigators studying the pathogenesis and treatment of PTE.

neuroscience↗