Biology subjects

Lo, E. H.

Publications and source records attributed to Lo, E. H..

5 recordsLinked to original sources

bioRxiv2025

Global hypoperfusion leads to a mismatch in oxygen delivery and consumption in the cerebral watershed area

Despite the pivotal role of pial collaterals in maintaining cerebral blood flow during focal brain ischemia, it is largely unexplored how the microvascular blood flow and oxygenation in the watershed "pial-collateral territory" differ from those in the territory supplied by the major arteries during chronic global hypoperfusion. To answer this question, we applied 2-photon microscopy and Doppler optical coherence tomography to investigate the changes in cerebral microvascular blood flow and partial pressure of oxygen (PO2), induced by bilateral common carotid artery stenosis (BCAS). The measurements were performed in the somatosensory cortex that is supplied by the middle cerebral artery (MCA), and in the adjacent watershed area in the awake, head-restrained C57BL/6 mice, via the chronic cranial window. The results showed that the BCAS induced a larger decrease in capillary red blood cell (RBC) flux in the watershed area than in the MCA territory, especially in the subcortical white matter. Besides, PO2 in the pial collaterals was significantly lower than that in the upstream MCA segments under control conditions. However, the PO2 changes in the arteries and veins under global hypoperfusion displayed different trends in the two interrogated regions, resulting in a significant increase in oxygen extraction fraction in the watershed area. These findings suggest a mismatch between oxygen supply and demand in the watershed area due to global hypoperfusion and increased subcortical white matter vulnerability. We have also observed dilation of the pial collaterals after BCAS, which might suggest a compensatory mechanism to improve the blood flow in the watershed under hypoperfusion.

neuroscience↗

bioRxiv2025

Imaging traumatic brain injuries in mice with potassium channel PET tracer 3F4AP

ObjectiveTraumatic brain injury (TBI) can lead to secondary injury, including axon and myelin damage, which contributes to long-term neurological deficits. The PET tracer [18F]3F4AP, a fluorinated derivative of the FDA-approved drug 4-aminopyridine, selectively binds to voltage-gated potassium (KV) channels, offering a novel approach to assess TBI-related node of Ranvier disruption and demyelination. This study evaluates [18F]3F4AP PET in penetrating and non-penetrating TBI models. MethodsEither controlled cortical impact (CCI, penetrating) or concussive (non-penetrating) TBI models were used to induce TBI in mice. Dynamic PET imaging with [18F]3F4AP was performed at time points of 0, 3, 7, 14, and/or 31 days post-injury (dpi), with quantitative analyses comparing tracer uptake in injured versus control regions. Luxol fast blue (LFB) staining was conducted to evaluate histological myelin loss. ResultsIn the CCI model, [18F]3F4AP PET imaging demonstrated a 34% increase in tracer uptake at the injury site at 7 dpi, correlating with histological evidence of demyelination. Tracer uptake gradually declined over time, reflecting potential remyelination. The concussive TBI model showed a smaller and more diffuse increase in uptake at 7 dpi compared to CCI. Conclusion[18F]3F4AP PET imaging effectively detects demyelination following TBI, with very high sensitivity in penetrating injuries. These findings highlight the potential of [18F]3F4AP as a valuable imaging biomarker for assessing TBI progression and/or therapeutic response. Further studies are warranted to explore its clinical applicability and comparison with other imaging modalities.

neuroscience↗

bioRxiv2024

Inhibition of nitric oxide synthase transforms carotid occlusion-mediated benign oligemia into de novo large cerebral infarction

It remains unclear why unilateral proximal carotid artery occlusion (UCAO) causes benign oligemia, without progressing to cerebral infarction, in mice, yet leads to a wide variety of outcomes (ranging from asymptomatic to death) in humans. We hypothesized that inhibition of NOS both transforms UCAO-mediated oligemia into full infarction and expands pre-existing infarction. In support, intraperitoneal administration of N{omega}-nitro-L-arginine methyl ester (L-NAME) followed by UCAO induced large-arterial infarction in mice, unlike UCAO alone. Six-hour laser-speckle-contrast imaging detected spreading ischemia in mice with infarction as assessed at 24h. In agreement with vasoconstriction/microthrombus formation shown by intravital microscopy, the NO-donor, molsidomine and the endothelial-NOS- activating antiplatelet, cilostazol, attenuated or prevented progression to infarction. Moreover, UCAO without L-NAME caused infarction in mice with hyperglycemia and hyperlipidemia, which, in turn, were associated with greater symmetric dimethylarginine (SDMA) levels. Further, increased levels of glucose and cholesterol associated with significantly larger infarct volumes in 438 consecutive patients with UCAO-mediated infarction. Lastly, Mendelian randomization identified a causative role of NOS inhibition, particularly in elevated SDMA concentration, in ischemic stroke risk. Therefore, NOS activity is a key factor determining the fate of hypoperfused brain following acute carotid occlusion, where SDMA could be a potential risk predictor.

neuroscience↗

bioRxiv2024

Transcriptomic analysis of the juvenile to adult transition in the mouse corpus callosum

The corpus callosum, a major white matter tract in the brain, undergoes age-related functional changes. To extend our investigation of age-related gene expression dynamics in the mouse corpus callosum, we compared RNA-seq data from 2-week-old and 12-week-old wild-type C57BL/6J mice and identified the differentially expressed genes (e.g., Serpinb1a, Ndrg1, Dnmt3a, etc.) between these ages. Interestingly, we found that genes highly expressed in myelinating oligodendrocytes were upregulated in 12-week-old mice compared to 2-week-old mice, while genes highly expressed in oligodendrocyte precursor cells (OPCs) and newly formed oligodendrocytes were downregulated. Furthermore, by comparing these genes with the datasets from 20-week-old and 96-week-old mice, we identified novel sets of genes with age-dependent variations in the corpus callosum. These gene expression changes potentially affect key biological pathways and may be closely linked to age-related neurological disorders, including dementia and stroke. Therefore, our results provide an additional dataset to explore age-dependent gene expression dynamics of oligodendrocyte lineage cells in the corpus callosum.

neuroscience↗

bioRxiv2023

Ultra-flexible endovascular probes for brain recording through micron-scale vasculature

Implantable neuroelectronic interfaces have enabled significant advances in both fundamental research and treatment of neurological diseases, yet traditional intracranial depth electrodes require invasive surgery to place and can disrupt the neural networks during implantation. To address these limitations, we have developed an ultra-small and flexible endovascular neural probe that can be implanted into small 100-micron scale blood vessels in the brains of rodents without damaging the brain or vasculature. The structure and mechanical properties of the flexible probes were designed to meet the key constraints for implantation into tortuous blood vessels inaccessible with existing techniques. In vivo electrophysiology recording of local field potentials and single-unit spikes has been selectively achieved in the cortex and the olfactory bulb. Histology analysis of the tissue interface showed minimal immune response and long-term stability. This platform technology can be readily extended as both research tools and medical devices for the detection and intervention of neurological diseases.

bioengineering↗