Biology subjects

Pavlova, I.

Publications and source records attributed to Pavlova, I..

4 recordsLinked to original sources

bioRxiv2024

Remote ischemic conditioning attenuates transneuronal degeneration and promotes stroke recovery via CD36-mediated efferocytosis.

BACKGROUNDRemote ischemic limb conditioning (RIC) has been implicated in cross-organ protection in cerebrovascular disease, including stroke. However, the lack of a consensus protocol and controversy over the clinical therapeutic outcomes of RIC suggest inadequate mechanistic understanding of RIC. The current study identifies RIC-induced molecular and cellular events in the blood that enhance long-term functional recovery in experimental cerebral ischemia METHODSNaive mice or mice subjected to transient ischemic stroke were randomly selected to receive sham conditioning or RIC in the hind limb at 2 h post-stroke. At 3d post-stroke, monocyte composition in the blood was analyzed, and brain tissue was examined for monocyte-derived macrophages (M{varphi}), levels of efferocytosis, and CD36 expression. Mouse with conditional deletion of CD36 in M{varphi} (cKOMM{varphi}) was used to establish the role of CD36 in RIC-mediated modulation of efferocytosis, transneuronal degeneration, and recovery following stroke. RESULTSRIC applied 2h after stroke increased entry of monocytes into the injured brain. In the post-ischemic brain, M{varphi} had increased levels of CD36 expression and efferocytosis. These changes in brain M{varphi} were derived from RIC-induced changes in circulating monocytes. In the blood, RIC increased CD36 expression in circulating monocytes and shifted monocytes to a proinflammatory LY6CHigh state. Conditional deletion of CD36 in M{varphi} abrogated the RIC-induced monocyte shift in the blood and efferocytosis in the brain. During the recovery phase of stroke, RIC rescued the loss of the volume and of tyrosine hydroxylase+ neurons in substantia nigra (SN) as well as behavioral deficits in WT mice, but not in cKOMM{varphi} mice. CONCLUSIONSRIC induces a shift in monocytes to a proinflammatory state with elevated CD36 levels, and this is associated with CD36-dependent efferocytosis in M{varphi}s that rescues delayed transneuronal degeneration in the post-ischemic brain and promotes stroke recovery. Together, these findings provide novel insight into our mechanistic understanding of how RIC improves in post-stroke recovery. Novelty and SignificanceO_ST_ABSWhat Is Known?C_ST_ABSO_LIInfiltrated monocyte-derived macrophages (M{varphi}) into the post-ischemic brain cause neural inflammation, but they also engage in efferocytosis that promotes tissue repair in the injured CNS. C_LIO_LIRemote ischemic limb conditioning (RIC) changes monocyte composition and enhances functional recovery in experimental brain ischemia. C_LIO_LIThe application of RIC is safe, feasible, and tolerable in stroke patients, but clinical outcomes remain inconsistent. C_LI What New Information Does This Article Contribute?O_LIWe provide experimental evidence that RIC modifies peripheral monocyte composition and molecular expression, and leads to favorable changes in debris clearance, structure integrity, transneuronal degeneration, and behavior following stroke. C_LIO_LIProtective effects of RIC disappear in the absence of CD36 in M{varphi}, suggesting an essential mechanistic role for CD36 in RIC-induced endogenous protective outcomes. C_LIO_LIThe current study demonstrates that immune-mediated RIC mechanisms facilitate inflammatory and recovery processes in the injured CNS. Given the challenges in directly manipulating the brain after stroke, the study suggests that RIC is a promising alternative strategy by inducing changes in peripheral monocytes that can influence injury progression and recovery. Moreover, RIC-induced peripheral changes uncovered by this study may serve as biomarkers to establish an optimal RIC protocol. C_LI

neuroscience↗

bioRxiv2022

Model-Informed Unsupervised Deep Learning Approaches to Frequency and Phase Correction of MRS Signals

PurposeA supervised deep learning (DL) approach for frequency-and-phase Correction (FPC) of MR spectroscopy (MRS) data recently showed encouraging results, but obtaining transients with labels for supervised learning is challenging. This work investigates the feasibility and efficiency of unsupervised DL-based FPC. MethodTwo novel DL-based FPC methods (deep learning-based Cr referencing [dCrR] and deep learning-based spectral registration [dSR]) which use a priori physics domain knowledge are presented. The proposed networks were trained, validated, and evaluated using simulated, phantom, and publicly accessible in-vivo MEGA-edited MRS data. The performance of our proposed FPC methods was compared to other generally used FPC methods, in terms of precision and time efficiency. A new measure was proposed in this study to evaluate the FPC method performance. The ability of each of our methods to carry out FPC at varying SNR levels was evaluated. A Monte Carlo (MC) study was carried out to investigate the performance of our proposed methods. ResultThe validation using low-SNR manipulated simulated data demonstrated that the proposed methods could perform FPC comparably to other methods. The evaluation showed that the dCrR method achieved the highest performance in phantom data. The applicability of the proposed method for FPC of GABA-edited in-vivo MRS data was demonstrated. Our proposed networks have the potential to reduce computation time significantly. ConclusionThe proposed physics-informed deep neural networks trained in an unsupervised manner with complex data can offer efficient FPC of MRS data in a shorter time.

neuroscience↗

bioRxiv2020

The diagonal band of broca continually regulates olfactory-mediated behaviors by modulating odor-evoked responses within the olfactory bulb

Sensory perception is modulated in a top-down fashion by higher brain regions to regulate the strength of its own input resulting in the adaptation of behavioral responses. In olfactory perception, the horizontal diagonal band of broca (HDB), embedded in the basal forebrain modulates olfactory information processing by recruiting olfactory bulb (OB) interneurons to shape excitatory OB output. Currently, little is known about how specific HDB to OB top-down signaling affects complex olfactory-mediated behaviors. Here we show that the olfactory bulb is strongly and differentially innervated by HDB projections. HDB-silencing via tetanus toxin light chain led to reduced odor-evoked Ca2+-responses in glomeruli of the OB, underscoring HDBs role in odor response modulation. Furthermore, selective, light-mediated silencing of HDB to OB afferents completely prevented olfactory-mediated habituation and discrimination behaviors. Notably, also social habituation and discrimination behaviors were affected. Mono-transsynaptic tracing studies indicated a robust HDB innervation from the paraventricular nucleus (PVN). Here we provide evidence for a novel tri-synaptic PVN-HDB-OB axis responsible for modulating these types of behavior. Thus, HDB to OB projections constitute a central top-down pathway for olfactory-mediated habituation and discrimination behaviors.

neuroscience↗

bioRxiv2019

DeepLabStream: Closing the loop using deep learning-based markerless, real-time posture detec-tion

In general, animal behavior can be described as the neuronal-driven sequence of reoccurring postures through time. Current technologies enable offline pose estimation with high spatio-temporal resolution, however to understand complex behaviors, it is necessary to correlate the behavior with neuronal activity in real-time. Here we present DeepLabStream, a highly versatile, closed-loop solution for freely moving mice that can autonomously conduct behavioral experiments ranging from behavior-based learning tasks to posture-dependent optogenetic stimulation. DeepLabStream has a temporal resolution in the millisecond range, can operate with multiple devices and can be easily tailored to a wide range of species and experimental designs. We employ DeepLabStream to autonomously run a second-order olfactory conditioning task for freely moving mice and to deliver optogenetic stimuli based on mouse head-direction.

animal behavior and cognition↗