Biology subjects

Kulkarni, P. P.

Publications and source records attributed to Kulkarni, P. P..

3 recordsLinked to original sources

bioRxiv2025

Psilocybin as a Treatment for Repetitive Mild Head Injury: Evidence from Neuroradiology and Molecular Biology

Repetitive mild head injuries incurred while playing organized sports, during car accidents and falls, or in active military service are a major health problem. These head injuries induce cognitive, motor, and behavioral deficits that can last for months and even years with an increased risk of dementia, Parkinsons disease, and chronic traumatic encephalopathy. There is no approved medical treatment for these types of head injuries. To this end, we tested the healing effects of the psychedelic psilocybin, as it is known to reduce neuroinflammation and enhance neuroplasticity. Using a model of mild repetitive head injury in adult female rats, we provide unprecedented data that psilocybin can reduce vasogenic edema, restore normal vascular reactivity and functional connectivity, reduce phosphorylated tau buildup, enhance levels of brain-derived neurotrophic factor and its receptor TrkB, and modulate lipid signaling molecules.

neuroscience↗

bioRxiv2023

Protection of β2GPI Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation

BackgroundAntibodies to {beta}2-glycoprotein I ({beta}2GPI) cause thrombosis in antiphospholipid syndrome, however the role of {beta}2GPI itself in regulation of coagulation pathways in vivo is not well understood. MethodsWe developed {beta}2GPI-deficient mice (Apoh-/-) by deleting exon 2 and 3 of Apoh using CRISPR/Cas9 and compared the propensity of wild-type (WT) and Apoh-/-mice to develop thrombosis using rose bengal and FeCl3-induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and assessed platelet activation in WT and Apoh-/- mice in the absence and presence of exogenous {beta}2GPI. ResultsCompared to WT littermates, Apoh-/- mice demonstrated a prolonged time to occlusion of the carotid artery after exposure to rose bengal or FeCl3, and reduced platelet and fibrin accumulation in cremasteric arterioles after laser injury. Similarly, significantly smaller thrombi were retrieved from the IVC of Apoh-/-mice 48 hours after IVC occlusion. The activated partial thromboplastin time (aPTT) and prothrombin time, as well as aPTT reagent- and tissue factor-induced thrombin generation times using plasma from Apoh-/- and WT mice revealed no differences. However, we observed significant prolongation of tail bleeding in Apoh-/- mice, and reduced P-selectin expression and binding of fibrinogen to the activated 2b{beta}3 integrin on platelets from these mice after stimulation with low thrombin concentrations; these changes were reversed by exogenous {beta}2GPI. An antibody to PAR3 blocked thrombin-induced activation of WT, but not Apoh-/- platelets, as well as the ability of {beta}2GPI to restore the activation response of Apoh-/- platelets to thrombin. {beta}2GPI deficiency did not affect platelet activation by a PAR4-activator peptide, or ADP. ConclusionsIn mice, {beta}2GPI may mediate procoagulant activity by enhancing the ability of PAR3 to present thrombin to PAR4, promoting platelet activation at low thrombin concentrations. Key PointsO_LI{beta}2GPI deficient mice are protected from experimental arterial, venous, and microvascular thrombosis. C_LIO_LI{beta}2GPI deficient mice display prolonged tail bleeding times and reduced PAR3-facilitated platelet activation by low concentrations of thrombin. C_LI

cell biology↗

bioRxiv2019

Prospects for transcranial temporal interference stimulation in humans: a computational study

Transcranial alternating current stimulation (tACS) is a noninvasive method used to modulate activity of superficial brain regions. Deeper and more steerable stimulation could potentially be achieved using transcranial temporal interference stimulation (tTIS): two high-frequency alternating fields interact to produce a wave with an envelope frequency in the range thought to modulate neural activity. Promising initial results have been reported for experiments with mice. In this study we aim to better understand the electric fields produced with tTIS and examine its prospects in humans through simulations with murine and human head models. A murine head finite element model was used to simulate previously published experiments of tTIS in mice. With a total current of 0.776 mA, tTIS electric field strengths up to 383 V/m were reached in the modeled mouse brain, affirming experimental results indicating that suprathreshold stimulation is possible in mice. Using a detailed anisotropic human head model, tTIS was simulated with systematically varied electrode configurations and input currents to investigate how these parameters influence the electric fields. An exhaustive search with 88 electrode locations covering the entire head (146M current patterns) was employed to optimize tTIS for target field strength and focality. In all analyses, we investigated maximal effects and effects along the predominant orientation of local neurons. Our results showed that it was possible to steer the peak tTIS field by manipulating the relative strength of the two input fields. Deep brain areas received field strengths similar to conventional tACS, but with less stimulation in superficial areas. Maximum field strengths in the human model were much lower than in the murine model, too low to expect direct stimulation effects. While field strengths from tACS were slightly higher, our results suggest that tTIS is capable of producing more focal fields and allows for better steerability. Finally, we present optimal four-electrode current patterns to maximize tTIS in regions of the pallidum (0.37 V/m), hippocampus (0.24 V/m) and motor cortex (0.57 V/m).

biophysics↗