New research from our lab out today 🧬🔬 Drug-resistant mesial temporal lobe epilepsy affects a large fraction of epilepsy patients and has been linked, for years, to both blood-brain barrier dysfunction and synaptic remodeling. The molecular bridge between the two has been missing in human tissue. We now mapped it, in the same patient samples. With our neurosurgery colleagues at USC, we took fresh resected tissue from patients with drug-resistant MTLE. From each patient we sampled two regions, the epileptic hippocampus and the less affected ipsilateral temporal pole, and split each piece into two fractions: brain microvessels and a vessel-depleted postsynaptic density fraction. Quantitative proteomics on all four fractions per patient then gave us a within-patient comparison of vessel and synaptic changes. Comparing hippocampus to temporal pole within each patient, we found: - In the microvessel fraction (1,541 proteins, 439 differentially expressed), tight-junction and endothelial adhesion proteins were lost, pericyte markers dropped, and fibrinogen, plasminogen, complement C3 and GFAP went up, with enrichment for complement and coagulation cascades. - In the PSD fraction (7,450 proteins, 1,881 differentially expressed), we saw the consequences of barrier leakage as protein infiltration into the parenchyma, plus disruption of pre- and postsynaptic signaling and loss of GABAergic interneurons. - Immunohistochemistry confirmed microvascular remodeling, pericyte loss, fibrinogen extravasation, microglial activation and presynaptic marker depletion in the hippocampus. - Ligand-receptor mapping points to a dysregulated ECM-integrin interface between vessels and parenchyma, and network-proximity analyses nominate candidate disease-modifying compounds. Congrats and big thanks to all authors, especially to Gavin Spillard to his 1st first-author paper :) @KECKSchool_USC @USC_ZilkhaNeuro @USC Preprint and interactive explorer linked in the comments!

This is the most comprehensive review on Alzheimer’s and inflammation I’ve read in a long time. Highly recommended for anyone interested in learning about AD research or future therapeutic possibilities in AD. nature.com/articles/s41577-0…

Biology operates across multiple scales, from molecules and genes to cells, genomes, and clinical data. Understanding all of it needs models that think across every level at once. We are seeing now exciting multi-scale models that can help us scientists with these tasks ⬇️

Stop asking for letters of recommendation in academia for every job/grant/award !!! These letters are usually 5% authentic, 70% copy-paste and 30% written by the student himself because the PI has no time 😅

Very cool study showing that BBB becomes impaired during aging and Alzheimer's disease due to changes in specific proteins (Glycocalyx), and restoring some of those in mice improves brain function and reduces damage. @wysscoray @Nature Paper: nature.com/articles/s41586-0…

Preprint alert!🚨 We as neuroscientists highly depend on behavioral testing in rodents 🐭. Still, assessing motor function or recovery can be so challenging⚡️. We aimed to change that using #deeplearning @DeepLabCut assisted 3D behavioral profiling biorxiv.org/content/10.1101/… 🧵1/

Single-cell profiling of the immune landscape across the entire human lifespan, very useful resource! @NatImmunol Paper: nature.com/articles/s41590-0…

Spatial transcriptomics of the aging mouse brain reveals origins of inflammation in the white matter | Nature Communications nature.com/articles/s41467-0…

Check out this gov proposal by @BioProtocol to support our reseach on psilocybin and stroke on @ResearchHub. This is amazing! Let me give everyone a bit of context on our proposed work 👇

🚨 New paper: Much of stroke research focuses on acute injury - but what changes in the brain one month after stroke? We mapped cellular and molecular shifts in the brain during the repair phase | J Neuroinflammation @BioMedCentral 🧬🧠 👇

Microglial NLRP3-gasdermin D activation impairs blood-brain barrier integrity through interleukin-1β-independent neutrophil chemotaxis upon peripheral inflammation in mice | Nature Communications nature.com/articles/s41467-0…

New paper🚨 The most important readout in any preclinical #therapy for #stroke⚡️is beahvior. Still, tests in 🐭are poorly reproducible + often unsuitable for unraveling complex recovery. We tried to change that using #DeepLearning, now out @BMCBiology bmcbiol.biomedcentral.com/ar… 🧵.1

Wow! First unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype–phenotype maps comprising CRISPR–Cas9-based knockouts of >20,000 genes in >30 million cells. Paper: nature.com/articles/s41592-0…

Ever thought the brain was immune privileged? Think again! Turns out brain's borders are more immunologically active than once thought, impacting cell therapies to the brain⚡️🧠 Our review about graft rejection + how to engineer cells for immune evasion cell.com/trends/molecular-me…

Important review on neuroferroptosis in health and diseases: nature.com/articles/s41583-0…

Visualizing PIEZO1 localization and activity in hiPSC-derived single cells and organoids with HaloTag technology | Nature Communications nature.com/articles/s41467-0…

New interesting preprints that I would like to highlight this week on @ResearchHub @ResearchHubF If you are interested in reviewing them, you can get paid and contribute to our mission to open science: Here’s what I picked for this week 🧠🧬 ⬇️

Some cool new preprints on @ResearchHub this week with a focus on cellular reprogramming, plasticity, and genetic engineering. Also, with a focus on different celltypes including neurons, microglia, pericytes etc! Check them out - and if you're an expert in any of these areas, write a review and earn $150 👇

Pericytes could help restore the blood-brain barrier in stroke & Alzheimer’s. But there’s a catch: They’ve only been studied under normal oxygen (normoxia). So, can they function in low-oxygen (hypoxic) conditions seen in these diseases? Our preprint: biorxiv.org/content/10.1101/…

Neither, use the 2ul pipette 100x (ofc reverse pipetting). This will give you the most accurate result

New review from our lab in @Brain1878 We explore how molecular blood-brain barrier (BBB) changes in aging, neurodegeneration and stroke affect disease progression, delivery of therapeutics, and much more! academic.oup.com/brain/advan…

Our review is now out in @Brain1878! We discuss how the blood-brain barrier can both help and hinder brain function and drug delivery. We focus on aging, stroke, and Alzheimer’s disease and how these conditions impact the BBB. Check it out (open access): academic.oup.com/brain/artic…

Amazing ShinyCell2 is out! Honestly, one of the most helpful tools to share single-cell and spatial RNAseq data. Can't wait to test v2 😀 ShinyCell2: An extended library for simple and sharable visualisation of spatial, peak-based and multi-omic single-cell data biorxiv.org/content/10.1101/…

Plasma proteomics identify biomarkers and undulating changes of brain aging | Nature Aging nature.com/articles/s43587-0…

Rapid and scalable personalized ASO screening in patient-derived organoids | Nature nature.com/articles/s41586-0…

My last three encounters with strangers were all like "Oh you're a neuroscientist?! Have you heard of @hubermanlab?" Followed by a 10-minute chat about cold showers, dopamine, and sunlight exposure. It's exciting to see how people are becoming more interested in neuroscience! 🧠

I reviewed this preprint on @ResearchHub and found it excellent, so I thought I'll share. If you like to learn how cholinergic interneurons in the striatum regulate serotonin release + how this may be linked to OCD or PD. Check it out incl my evaluation: researchhub.com/paper/857940…

Brain pericytes and perivascular fibroblasts are stromal progenitors with dual functions in cerebrovascular regeneration after stroke | Nature Neuroscience nature.com/articles/s41593-0…

Single-cell spatial transcriptomic atlas of the whole mouse brain: Neuron cell.com/neuron/fulltext/S08…

🚨Preprint: Stroke recovery is complex & involves major changes to all brain cell types. We dissect underlying molecular mechanisms in the repair phase 1 month post-stroke "A molecular brain atlas reveals cellular shifts during the repair phase of stroke" biorxiv.org/content/10.1101/…

Highly recommended: Changing genes, cells and networks to reprogram the brain after stroke | Nature Neuroscience nature.com/articles/s41593-0…

Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease | Nature Medicine nature.com/articles/s41591-0…

My selection of preprints that I found interesting this week. They cover organoid models, genomics, connectomics, and neurodegeneration. Get paid $150 by providing a high quality review and contribute to our mission to accelerate open science @ResearchHub @ResearchHubF 🧵

Macrophage-augmented organoids recapitulate the complex pathophysiology of viral diseases and enable development of multitarget therapeutics | Nature Biomedical Engineering nature.com/articles/s41551-0…

New preprint🚨 We generated human brain pericytes from pluripotent stem cells. They show strong molecular & functional similarities to primary human brain pericytes Transplanted into pericyte-deficient mice, they formed hybrid human-mouse microvessels🐭 biorxiv.org/content/10.1101/…

Anesthetic agents have been previously shown to have neuroprotective effects in stroke. This interesting preprint @ResearchHub shows how mitochondrial function is involved in the protective effects (especially GDF15, ATF5). Read the preprint + my review: researchhub.com/paper/857940…

Just discovered this article, very insightful how small sample sizes can negatively affect reliability in (preclinical) neurosciences: nature.com/articles/nrn3475#…

We love pericytes❤️but we also love open and transparent science. Therefore, I uploaded this work and will upload all our future preprints to @ResearchHub @ResearchHubF to receive community feedback and contribute to the future of science! researchhub.com/paper/937987…

Transforming the understanding of brain immunity | Science science.org/doi/10.1126/scie…

Very cool! Quasi-spatial single-cell transcriptome based on physical tissue properties defines early aging associated niche in liver. Wonder if this could also work in the aging brain (after stroke?)? nature.com/articles/s43587-0…

That's cool - an update from edgeR ! Can't wait to test it! edgeR v4: powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets Paper: academic.oup.com/nar/article…

Cool study showing that Glut1 deletion in astocytes enhances glucose metabolism and resilience to stroke Full paper: nature.com/articles/s41467-0…

It is kind of funny how many CNS papers have been published debating whether adult neurogenesis truly exists in humans…😂😅 to be fair quite a convincing study here: science.org/doi/10.1126/scie…

Brain endothelial gap junction coupling enables rapid vasodilation propagation during neurovascular coupling: Cell cell.com/cell/fulltext/S0092…

Myeloid lineage C3 induces reactive gliosis and neuronal stress during CNS inflammation | Nature Communications nature.com/articles/s41467-0…

These are the most interesting preprints on @ResearchHub that I read last week in the field of neuroscience, incl. microglia, reward processing, cortical circuits, development, and Alzheimer's. They still need your review (+ you can get paid for high quality contributions)

Cool preprint by Adams et al. showing that pericytes are organ-specific regulators of tissue morphogenesis: researchsquare.com/article/r…

Most read review in @ImmunityCP about the dynamic interplay of brain-resident, meningeal, and systemic immune cells in stroke and dementia

New preprint! 🚨@KeckMedicineUSC @uzh_irem We started with the simple question: What happens when we transplant stem cells into a mouse model of #stroke, and what are the interactions between graft and host? Took us only 5 yrs to find out😀: biorxiv.org/content/10.1101/… 1/10 🧵

New interesting preprints that I would like to highlight this week on @ResearchHub @ResearchHubF If you are interested in reviewing them, you can get paid and contribute to our mission to open science: Here’s what I picked for this week 🧠🧬 ⬇️:

A selection of interesting preprints for this week: we cover aging, Alzheimer's, Parkinson's, motor learning, and brain development. If you're an expert in any of these topics, you can earn $150 for a high-quality peer review and contribute to open science 👇

Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease | Nature Medicine nature.com/articles/s41591-0…

Neuroinflammation and hypoxia promote astrocyte phenotypic transformation and propel neurovascular dysfunction in brain arteriovenous malformation | Journal of Neuroinflammation jneuroinflammation.biomedcen…

Our most recent review on how neural stem cell therapy promotes brain repair after stroke @stemcellreports @ISSCR Here the summary:

Few interesting preprints that I would like to highlight this week on @ResearchHub If you are interested in reviewing them, you can earn 150$ and contribute to our mission to open science:

🚨 Our new study out in Advanced Science @AdvPortfolio! "Time is Brain" - is also true for cell therapies! Our work shows that delaying neural stem cell (NSC) therapy after stroke avoids the hostile early environment, increasing cell therapy success! 🧠 Transplanting NPCs at 7 (vs. 1) days post-stroke leads to: → 5x greater graft survival → Increased early NPC proliferation → Widespread axonal outgrowth into brain tissue

This week, I want to specifically highlight Alzheimer’s disease and related dementia preprints that I invite you to review, with a $150 reward for a high-quality contribution. Some keywords are: blood-brain barrier dysfunction, AD mouse models, scRNAseq, lyosomal pathways, gut inflammation etc. My favorite is the first study on 5xFAD mice + BBB Check these out on @ResearchHub @ResearchHubF

New review out in @NatRevNeurol. We explore biomarkers for vascular cognitive impairment and dementia (VCID) describing pathopysiology like atherosclerosis, ischemia, BBB breakdown + key molecules involved. 👏 to Satoshi + team! #VCID #DementiaResearch nature.com/articles/s41582-0…

Amyloid-associated hyperconnectivity drives tau spread across connected brain regions in Alzheimer’s disease | Science Translational Medicine science.org/doi/10.1126/scit…

Very cool, I think we need more of these type of protocols to improve reproducibility in science e.g. how to isolate oligodendrocytes, microglia, endothelial cells, astrocytes, and neurons from a single mouse brain using magnetic-activated cell sorting biorxiv.org/content/10.1101/…

Pericytes are crucial for maintaining the blood-brain/retina barrier, but some subtypes may contribute to CNS pathology. I reviewed this preprint showing that PTTG1-pericytes are involved in diabetic retinopathy @ResearchHub. Check preprint + my review: researchhub.com/paper/863529…

A brain-specific angiogenic mechanism enabled by tip cell specialization | Nature nature.com/articles/s41586-0…

Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity | Nature Aging nature.com/articles/s43587-0…

Astrocyte priming enhances microglial Aβ clearance and is compromised by APOE4 nature.com/articles/s41467-0…

New interesting preprints that I would like to highlight this week on @ResearchHub @ResearchHubF If you are interested in reviewing them, you can get paid and contribute to our mission to open science: Here’s what I picked for this week 🧠🧬 ⬇️

New research I’d like to highlight this week—covering Alzheimer’s disease, brain vasculature, spinal cord injury, stem cells and more! Earn $150 by reviewing any of these papers on @ResearchHub @ResearchHubF

Can stem cells repair the stroke-injured brain? And what are the underlying mechanisms? We talk about evidence for direct cell replacement, release of supportive factors, safety, immune evasion, graft-host interactions and more! Published in @Brain1878 academic.oup.com/brain/advan…

Immune checkpoint TIM-3 regulates microglia and Alzheimer’s disease | Nature nature.com/articles/s41586-0…

A new review from our lab exploring how the blood-brain barrier (BBB) can be used as a treatment target for neurodegenerative disorders tandfonline.com/doi/10.1080/… TL;DR → Here are a few key highlights 👇

A quick use case I wanted to share about why I’m so excited about @ResearchHub: ✅ A grant proposal was submitted 2 weeks ago: researchhub.com/post/4086/br… ✅ A detailed, high-quality review was posted 9 days ago: researchhub.com/post/4086/br… ✅ The author @breath_Guy responded within 24 hours with thoughtful comments and rationales. A completely transparent process, completed in under 2 weeks. This is something that can take up to 1 YEAR in traditional funding systems. And this is just one of many examples happening on @ResearchHub @ResearchHubF

Astrocyte-derived CXCL10 exacerbates endothelial cells pyroptosis and blood–brain barrier disruption via CXCR3/cGAS/AIM2 pathway after intracerebral hemorrhage nature.com/articles/s41420-0…

Morphodynamics of human early brain organoid development | Nature nature.com/articles/s41586-0…

So happy to share 😀; I am now group leader @uzh_irem @UZH_Science in "Cell therapy for Brain Regeneration". So, I thought this is a good moment to briefly introduce what we are doing in our lab and how we see the future of #celltherapy in #stroke and other brain injuries. 1/6

🧵Another exciting week of preprints featured on @ResearchHub @ResearchHubF! Check out the latest work on stroke, Alzheimer's disease, spatial transcriptomics and more... We would appreicate your review on any of those preprints! 👇

Can psilocybin protect the human brain after stroke? We just pre-registered our study on @ResearchHub exploring this exact question. Here’s what we’re doing and why we believe it could change stroke therapy 👇🧵 researchhub.com/fund/4261/ef…

Cool study if you’re interested in blood–brain barrier disruption, inflammation, and aging in mice academic.oup.com/braincomms/…

Interesting perspective article showing the role of cellular senescence (often associated with aging) in normal physiology | Science science.org/doi/10.1126/scie…

Triglycerides are an important fuel reserve for synapse function in the brain | Nature Metabolism nature.com/articles/s42255-0…

Longitudinal Investigation of Brain and Spinal Cord Pericytes After Inducible PDGFRβ+ Cell Ablation in Adult Mice - Atak - 2025 - Journal of Neurochemistry - Wiley Online Library onlinelibrary.wiley.com/doi/…

Endothelial cell metabolism in cardiovascular physiology and disease | Nature Reviews Cardiology nature.com/articles/s41569-0…

Interesting finding that neural stem cells exist outside the brain/spinal cord-in tissues like lung & tail-and share key properties with brain NSCs, challenging current dogma. Wonder if these NSCs exist in humans & can show similar therapeutic potential nature.com/articles/s41556-0…

Check our preprint describing the proteome signature of iPSC-derived brain #pericytes + how they functionally replace missing pericytes, create hybrid microvessels, and stop #BBB leaks in mouse brains. Could this hint at new directions for #CellTherapy? biorxiv.org/content/10.1101/…

100% agree. For context, $40B is nearly the annual budget of the entire NIH. We need to transform the publishing system, make articles freely available at low cost, and fairly compensate reviewers. @ResearchHub @ResearchHubF

Join the discussion started by @brian_armstrong on @ResearchHub What are the highest potential areas of research that are underfunded today? researchhub.com/post/4329/wh…

Repair-associated macrophages increase after early-phase microglia attenuation to promote ischemic stroke recovery | Nature Communications nature.com/articles/s41467-0…

What are the best tools for to connect biological pathways to existing therapeutics? Check out this post on @ResearchHub There are so many useful answers in this discussion. I’ve been using omics for 10 years, and I still learned about new tools: researchhub.com/question/390…

Using the amazing @DeepLabCut we were able to track every movement of all relevant anatomical landmarks of the mouse in 3D, without even marking the joints beforehand (with an accuracy of nearly 100%) .3

Interesting study showing that microglial cyclooxygenase-1 modulates cerebral capillary basal tone in vivo in mice nature.com/articles/s41467-0…

Screening and Identification of Brain Pericyte‐Selective Markers onlinelibrary.wiley.com/doi/…

Endothelial cells regulate astrocyte to neural progenitor cell trans-differentiation in a mouse model of stroke | Nature Communications nature.com/articles/s41467-0…

I receive regular requests how to quantify #vasculature in the #brain. We have published 1 year ago a straightforward tool that does not require any coding experience and works with @FijiSc. (1/5) So, I thought a little thread might be useful for some frontiersin.org/articles/10.…

Happy to announce that I received the @snf_ch Spark grant that aims to fund unconventional and high-risk projects! 🥳 🥳 We plan to develop new brain-shuttle systems to transport stem cells across the #BBB and to overcome major limitations of current cell therapies; stay tuned!

Even after >10 yrs in academia the smartest thing I've seen a scientist do was back when I was a grad student. To get around a word limit, a student just colored some letters white and put 'em between the words. Whenever I am faced with word restriction,the memory comes to mind😂

Important study @eLife showing that alzheimer-mutant γ-secretase complexes stall amyloid β-peptide production: elifesciences.org/reviewed-p…

We are adapting our behavior analysis following #stroke in mice to the state of art @DeepLabCut. A fantastic tool for markerless pose estimation with #DeepLearning. Stay tuned and #trackmeifyoucan for more detailed kinematic analysis coming soon! @uzh_irem @UZH_en

Multiregional blood-brain barrier phenotyping identifies the prefrontal cortex as the most vulnerable region to ageing in mice biorxiv.org/content/10.1101/…

Metabolic adaptations direct cell fate during tissue regeneration | Nature nature.com/articles/s41586-0…

I reviewed this interesting preprint for @GigaScience on @ResearchHub The authors propose a new clustering method for high-dimensional biological data, applicable to flow/mass cytometry, scRNA-seq + multiplex imaging. Check the preprint + my review: researchhub.com/paper/667084…

Strokes are highly heterogenous. Therefore, it may be too naive to assume that there's ONE therapy that can regenerate every type of #stroke Read our @brainpathol comment on cell therapies in white matter strokes. And why here #astrocytes may be a better cell source than NPCs

Cool preprint study showing the role of IPSC-pericytes in maintaining BBB integrity during viral infection in a BBB model biorxiv.org/content/10.1101/…

New interesting preprints that I would like to highlight this week on @ResearchHub @ResearchHubF Earn 150$ in reviewing them + contribute to our mission to open-science! My picks for this week with a focus on Alzheimer's disease, cerebral blood flow, genomics and the BBB 🧠🧬⬇️