Jialing Liu, PhD
Our research endeavors to improve the recovery of function after ischemic stroke and brain injuries, in the context of neural regeneration and vascular remodeling.
Emerging evidence suggests that metabolic syndrome, type II diabetes in particular, is associated with an increased risk of stroke and poor functional outcome, yet the mechanisms underlying this predicament are unclear. Collateral status is an independent predictor of stroke outcome, as well as response to thrombolytic therapies in patients with ischemic stroke. Using Doppler Optical Coherence Tomography, we determine the extent of retrograde collateral flow in the leptomeningeal circulation and how it contributes to the outcome and recovery after ischemic stroke. To dissect the mechanisms underlying the impaired collateral status seen in mice with type II diabetes after ischemic stroke at the vascular level, we investigate the role eNOS and neuroinflammation using transgenic mouse models. We determine the inflammatory cell profiles during the acute and chronic stages of stroke by Fluorescence Activated Cell Sorter. To understand the contribution of diabetes-associated hypercoagulability to impaired collateral flow, we employ Multiphoton Laser Scanning Microscopy to detect and image blood clots and cell aggregates in MCA branches after stroke. Ongoing research also deciphers how estrogen impacts collateral flow in females with metabolic syndrome.
We have shown that ischemic stroke, hypoglycemic or traumatic brain injuries induced the proliferation and differentiation of endogenous neural stem cells. Additional evidence suggest that conditional ablation of neuroprogenitor cells in adult mice impeded post stroke cognitive recovery and reduces synaptic connectivity in the perforant pathway, consistent with our earlier results that neurogenesis contributed to post stroke functional recovery. Despite an increase in new neurons immediately after brain injury, only a small fraction of them survived longer than one month. Ongoing work seeks to enhance neurogenesis and promote functional recovery by behavioral rehabilitation or pharmacological interventions. Considering the close relationship between neural and vascular regeneration, molecules like Netrins are implicated in both neurogenesis and angiogenesis. Ongoing studies will investigate how Netrin-1 gene therapy promotes the recovery of neurovascular unit and function after ischemic stroke.
The decline of cognitive function after stroke is not uncommon, yet the neurobiology of this disability is not well understood. Hippocampus, the brain region specializing in memory, is physically distant from the primary stroke site in the cerebral cortex and is unharmed by the stroke insult. Recent advances in functional connectivity suggest that shared neuronal activation patterns define brain networks linking anatomically separate brain regions. Several cortical areas that are affected by stroke are also strongly interconnected by remote brain regions including the hippocampus, raising the possibility that a disruption of the connection between cortex and hippocampus due to stroke can result in dysfunction of the latter, thus leading to memory impairment. Using multichannel in vivo electrophysiology, we determine the temporal profile of stroke-induced changes in brain oscillation patterns in the hippocampus. Ongoing investigations will establish how brain oscillation can be used to predict the outcome and recovery after ischemic stroke.