Our interest:
How do spreading depolarizations impact the brain during and after stroke or seizure?
Ischemic brain tissue is permissive to sequelae that influence brain-wide activity and influence stroke outcome, including seizure, rhythmic hypersynchronous neuronal activity propagating rapidly across networks, and spreading depolarization (SD), slow pan-cellular depolarization waves propagating through contiguous grey matter.
SDs in peri-infarct tissue are generated from a metabolic supply-demand mismatch and considered deleterious. We observed seizure-induced SD (sSD) in remote contralesional tissue during the acute phase of stroke that improved hippocampal function during recovery.
We are ultimately interested in how these unique presentations of spreading depolarization impact brain structure and function at both the subcellular and whole animal level.
Our approach:
in vivo & in vitro methods to visualize and record seizure and stroke neurobiology in real-time.
The models. We induce and monitor ischemic stroke (via photothrombosis) or trigger seizures and SD in the naive brain (via optogenetics) of freely behaving mice.
The technology. We use a combination of in vivo approaches allowing us to record SD and changes in brain activity.
The technology. We also use multimodal microscopy approaches to understand how tissue microstructure responds to pathological conditions.
Our lab is currently focused on the role of spreading depolarization in the hippocampus, a phenomenon that occurs during stroke, epilepsy, and potentially in other pathological situations.
Our impact:
Improving stroke care. While middle cerebral artery (MCA) occlusions make up half of large vessel human strokes and have well-established preclinical models, deep brain strokes are less understood and have fewer available preclinical models due to limited access to induce/record stroke, particularly in awake conditions. About 30% of non-MCA strokes occur in posterior cerebral artery (PCA)-fed territory, the vasculature that supplies the hippocampus. Hippocampal strokes trigger devastating and unique symptoms, including transient or permanent amnesia and increase risk of major neurological disorders. Our model has the unique flexibility to target any brain region in an awake and behaving mouse (absent of anesthesia, which is known to be protective during stroke). With this in mind, we can better understand the unique neurobiology and symptomology of deep brain stroke.
Understanding how tissue context determines the impact of SD on brain function in stroke and seizure. Our group aims to understand how tissue context (ie. brain region, perfusion status, past exposure to pathological stimuli, etc.) dictates the cognitive and behavioral effects of SD occurring in the context of seizure, stroke, or where these two pathologies meet. We hope this can inform treatment of patients in neurocritical care, as well as patients experiencing epilepsy.