Biology subjects

Duhaime, A.-C.

Publications and source records attributed to Duhaime, A.-C..

2 recordsLinked to original sources

bioRxiv2023

Release of extracellular matrix components after human traumatic brain injury

Most research on the evolution of damage after traumatic brain injury (TBI) focuses on cellular effects, but the analysis of human tissue slices and animal research have shown that TBI causes concomitant damage in the extracellular matrix, which can play a significant role in both short-term consequences such as edema, and late effects such as post-traumatic epilepsy (PTE). To test the hypothesis that traumatic brain injury (TBI) in human patients causes disruption of sulfated glycosaminoglycan (sGAG) in the extracellular matrix, we measured levels of these substances in the ventricular cerebrospinal fluid (CSF) in patients with severe TBI in the acute post-injury period, along with concomitant levels in blood and urine. We assessed whether levels corresponded to parenchymal injury load, distance of traumatic brain lesions from the ventricle, presence of polytrauma, or host demographic factors. MethodsSamples of CSF, blood, and urine were obtained within 72 hours of injury in patients who received external ventricular drains as part of their treatment of severe TBI, and levels of chondroitin and heparan sGAGs were measured, along with their disaccharide constituents. Basic demographic information, presence and severity of polytrauma, brain injury load based on imaging findings, and distance of radiologically visible parenchymal injury from the ventricle were analyzed for correlation with total subtype sGAG levels in each patient. ResultsLevels were measured in 14 patients ranging in age from 17-90 years. CSF sGAG levels were variable among patients, and sGAG levels were higher in plasma than in CSF and variable in urine. Patients with polytrauma had non-significantly higher blood sGAG compared to patients with isolated head injury. Subcategories of CSF sGAG levels correlated with distance from the ventricle of parenchymal injury but not with brain injury load, which may reflect rapid metabolism in the parenchyma, contamination by blood, or bulk directional CSF flow from the ventricle to the subarachnoid space. ConclusionThis study is the first to measure sGAG levels in ventricular CSF and also provides the first measurements in patients with TBI. Damage to the extracellular matrix may play a major role in acute and chronic injury sequelae, and these data demonstrate elevation locally of intracranial sGAGS after severe TBI and also suggest rapid local metabolism of these breakdown products. The consequences of extracellular matrix breakdown may provide unique therapeutic and preventive avenues to mitigate post-injury sequelae.

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↗