BBTΔ Lab

Colossal Bioscience did not revive dire wolves, despite a sensationalist Time Magazine cover story.

Making genetically modified animals that are cosplaying as extinct species is not de-extinction.

Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow - Journal of Neuroinflammation Background Immunothrombosis is the process by which the coagulation cascade interacts with the innate immune system to control infection. However, the formation of clots within the brain vasculature c...

Insight into the host-pathogen interactions of a CNS parasite within the brain vasculature. #BloodBrainBarrier

Glutamatergic argonaute2 promotes the formation of the neurovascular unit in mice Neurovascular unit formation is mediated by Ago2-dependent repression of PTEN in excitatory neurons.

Very cool new paper showing that Ago2 gene in glutamatergic neurons is critical for the formation of cerebral blood vessels in the developing mouse brain 🤩 #cerebrovascular

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 👇

Immunostaining of a mouse brain blood vessel.

Immunostaining of a mouse brain blood vessel with Collagen type 4 (cyan) and GFAP (orange) Nuclei have been visualized by DAPI staining (blue).
#FluorescenceFriday
#bloodbrainbarrier

Fluorescence Friday! Ipsc derived endothelial cells (green/ red- tight junction proteins, blue-nucleus) #Bloodbrainbarrier #ipsc #stem #neuroscience

#FluorescenceFriday is a thing? Here is my submission: GFAP positive #astrocytes (red) projecting aquaporin 4 positive endfeet (green) onto blood vessels in the mouse cortex. It’s good for me, good for you, and great for the #bloodbrainbarrier

Regulation of blood-brain barrier integrity by Dmp1-expressing astrocytes through mitochondrial transfer A subset of astrocytes expressing Dmp1 helps maintain blood-brain barrier by transferring mitochondria to endothelial cells.

Not all astrocytes regulate blood-brain barrier integrity, but those expressing Dmp1 apparently do ! #cerebrovascular #BloodBrainBarrier www.science.org/doi/10.1126/...

#NeuroArtFriday #FluorescenceFriday #BloodBrainBarrier

Why is brain waste clearance essential for tackling age-related neurological decline? A brand new review co-written by Dr A Drieu, group leader @ipnp.bsky.social summarizes current knowledge on this important topic- please read!
pubmed.ncbi.nlm.nih.gov/39395409/
@inserm.fr #bloodbrainbarrier

Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system - Nature Materials A lipid-nanoparticle-based formulation incorporating engineered lipids containing a blood–brain-barrier-crossing moiety effectively delivers mRNA to neurons and astrocytes following systemic administr...

“Study shows these #BloodBrainBarrier -crossing lipid nanoparticles can safely & efficiently deliver mRNA into brain & opens up opportunities to use mRNA-based therapies for variety of neurological & psychiatric disorders”-@yizhoudonglab.bsky.social. Learn More: www.nature.com/articles/s41...

Great new work from my colleagues from the @hajimehirase.bsky.social lab. Check out their fluorescent mouse line and viruses available on Addgene and on request. #bloodbrainbarrier #neuroscience

During deep sleep, exercise and other select times, our blood-brain barrier creaks open to let in just the right molecules. Scientists are increasingly seeing the barrier as a dynamic system. (From 2023) www.quantamagazine.org/how-the-brai...

In vivo & In vitro Causal evidence of #EndothelialCell #Senescence as a driver of #Aging-related Compromise of #BloodBrainBarrier

Old INK-ATTC🐭(p16-hi cell elimination)

Senescent+ Healthy EC co-culture

#Aging_Cell 2024
onlinelibrary.wiley.com/doi/full/10....

Microplastics in the bloodstream can induce cerebral thrombosis by causing cell obstruction and lead to neurobehavioral abnormalities Microplastics get in the blood and are eaten by immune cells, leading to cell obstruction and cerebral thrombosis.

This week #JournalClub @labsoap.bsky.social on #microplastic #bloodbrainbarrier #plastifou in @science.org
www.science.org/doi/10.1126/... 🧠🏭🍃

Blood-Brain Barrier Transport in Aging and Alzheimer’s Disease The NIA hosted the Blood-Brain Barrier Transport in Aging and Alzheimer’s Disease Workshop on April 24-25, 2024, discussing BBB transport mechanisms, drug delivery strategies, and research gaps.

In case you missed this spring's NIH workshop on "Blood-Brain Barrier Transport in Aging and Alzheimer’s Disease," the meeting summary is now available. Check it out! #bloodbrainbarrier #Alzheimers #aging www.nia.nih.gov/research/dn/...

Activation of Wnt/β-catenin in neural progenitor cells regulates blood–brain barrier development and promotes neuroinflammation - Scientific Reports Scientific Reports - Activation of Wnt/β-catenin in neural progenitor cells regulates blood–brain barrier development and promotes neuroinflammation

www.nature.com/articles/s41... #BloodBrainBarrier #Zebrafish

Peptide-Functionalized Lipid Nanoparticles for Targeted Systemic mRNA Delivery to the Brain Systemic delivery of large nucleic acids, such as mRNA, to the brain remains challenging in part due to the blood-brain barrier (BBB) and the tendency of delivery vehicles to accumulate in the liver. Here, we design a peptide-functionalized lipid nanoparticle (LNP) platform for targeted mRNA delivery to the brain. We utilize click chemistry to functionalize LNPs with peptides that target receptors overexpressed on brain endothelial cells and neurons, namely the RVG29, T7, AP2, and mApoE peptides. We evaluate the effect of LNP targeting on brain endothelial and neuronal cell transfection in vitro, investigating factors such as serum protein adsorption, intracellular trafficking, endothelial transcytosis, and exosome secretion. Finally, we show that LNP peptide functionalization enhances mRNA transfection in the mouse brain and reduces hepatic delivery after systemic administration. Specifically, RVG29 LNPs improved neuronal transfection in vivo, establishing its potential as a nonviral platform for delivering mRNA to the brain.

Breakthrough Research! @upenn.edu Bioengineers Emily Han, Michael Mitchell, et al. have modified lipid nanoparticles (LNPs) to not only cross the #BloodBrainBarrier (BBB) but also to target specific types of cells, including neurons.

Learn More in Nano letters
pubs.acs.org/doi/10.1021/...

Neurovascular dysfunction in psychiatric disorders: Underlying mechanisms and therapeutic approaches The neurovascular unit (NVU) is present in both brain and retinal barriers and consists of endothelial cells, basement membrane, pericytes, glial cells (astrocytes and microglia) and neurons. Barrier...

Nice review highlighting the associations between neuropsychiatric conditions and #cerebrovascular deficits doi.org/10.1111/eci.... #BloodBrainBarrier #Psychiatry

Researchers Target Brain Blood Vessels in Mice With COVID “Brain Fog” Researchers have identified a mechanism that causes neurological problems in mice infected with the virus behind COVID-19, and also found a treatment that helped prevent these changes.

Researchers Target Brain Blood Vessels
in Mice With COVID “Brain Fog”

Engineered Wnt7a ligands rescue blood-brain barrier and cognitive deficits in a COVID-19 mouse model
academic.oup.com/brain/advanc...

#BloodBrainBarrier #WntBetaCateninPathway

www.technologynetworks.com/neuroscience...

#BloodBrainBarrier

Induced #EndothelialCell Claudin 5 KO (but not Cldn5 -/+) in adult🐭➡️ #BBB leakage (1~10 kDa, but not 70 kD)

Cldn5-null ECs (15% of total ECs) have minimal vs Cldn5-intact ECs➡️non-cell-autonomous impact secondary to BBB leak

#CellRep 2024
www.sciencedirect.com/science/arti...

Third instar larval brain of the genotype [repo-Gal4 UAS-PGRP-LE STAT92E::GFP mdr65-tdTomato] stained for STAT activity (anti-GFP staining, green), subperineurial glial cells (anti-dsRed staining, magenta), and neural lamella (anti-Laminin staining, blue). Credit: Bente Winkler.

The #BloodBrainBarrier (BBB) prevents immune cells & pathogens from entering the brain. @b-wink.bsky.social &co show that during #neuroinflammation in #Drosophila, immune cells can cross the BBB by degrading its ECM through a JAK/STAT-regulated pathway 🧪 @plosbiology.org plos.io/4k1TTIG

3D #BloodBrainBarrier #OrganOnAChip

#Microfluidic Fibrin

#hiPSC-#EndothelialCell
👤🧠Brain vascular #Pericyte (no apparent wrapping)
Primary or hiPSC-Astrocyte

Astrocyte⏫#VascularPermeability & Vascular length density, ⬇️by cAMP or flow

#StemCellReports 2024
www.sciencedirect.com/science/arti...

A multicolored confocal microscopy image with blood-brain barrier cells in a microfluidic device on a black background. Red colored endothelial cells are in the left channel, green astrocytes, and purple pericytes are in the right channel. The channels are connected by small openings

Confocal microscopy image of endothelial cells highlighting their tight junction proteins in yellow (ZO-1) and red (Claudin 5) on a black background

A new #FluorescenceFriday for today! ✨🔬🧠

My 1st time assembling a full #BloodBrainBarrier in a #microfluidic device.

🔴 Claudin 5 (endothelial protein)
🟡 ZO-1 (endothelial protein)
🟢 GFAP (astrocytes)
🔵 DAPI (cell nuclei)
🟣 NG2 (pericytes)

#neuroskyence #neuroscience #bbb #microscopy #confocal

Astrocytic cannabinoid receptor 1 promotes resilience by dampening stress-induced blood–brain barrier alterations - Nature Neuroscience The mechanisms of neurovascular adaptations underlying stress resilience remain unclear. Here the authors show that the astrocytic endocannabinoid system modulates the blood–brain barrier changes duri...

I hope you haven’t missed this awesome new study by
@caromenard666.bsky.social’s team, where the dreamy keys worlds #astrocyte and #BloodBrainBarrier coexist 🤩🥰

How does exercise and fitness promote healthy brain aging?
An outstanding, comprehensive review @thelancet.bsky.social
reduced neuroinflammmation, preserves blood-brain-barrier, neurogenesis, role of exerkines, and much more
www.thelancet.com/journals/lan...

Lina Stern, a biochemist and neurophysiologist, was one of the first researchers to identify what is now known as the blood-brain barrier, and conducted pioneering research on the central nervous system.
adalovelaceday.subst...

On the cover: The blood-brain barrier is a defining feature of brain tumors, shaping their biology and therapeutic response. In this issue, Bejarano et al. use single-cell RNA sequencing and spatial analysis to construct a vascular atlas of primary and metastatic brain tumors, revealing distinct alterations in endothelial and mural cells. Glioblastomas undergo substantial vascular remodeling compared to low-grade gliomas, while brain metastases exhibit even greater permeability and increased immune cell interactions. This unveiling of vascular heterogeneity is depicted as a red pencil coloring in the intricate details of tumor-associated blood vessels within a map of the human brain wherein a tumor is surrounded by diverse immune cells. Image by Joana C. Carvalho.

Excited to see our image on the cover of #Immunity today 🤩

Congrats to the amazing @lbejarano.bsky.social & all authors for our #brain #tumor #vasculature study

www.cell.com/immunity/ful...

Huge 🙏 🙏 to the v talented @joanagcc.bsky.social for creating this super cover 🧠🧪

@cp-immunity.bsky.social

DNA-guided transcription factor interactions extend human gene regulatory code - Nature A large-scale analysis of DNA-bound transcription factors (TFs) shows how the presence of DNA markedly affects the landscape of TF interactions, and identifies composite motifs that are recognized by ...

Read ‘DNA-guided transcription factor interactions extend human gene regulatory code’ from @sangerinstitute.bsky.social and @cambridgeuni.bsky.social in @nature.com, here ⬇️

bit.ly/3RFmwhN