Lightnews — Scholar-powered news

Amy Gleichman @amygleichman.bsky.social · 36m

Thanks Michael!

Amy Gleichman @amygleichman.bsky.social · 36m

Thanks, Louise!

Amy Gleichman @amygleichman.bsky.social · 15h

You’re not sorry 😂 and thanks! Hope to catch up one of these days

1

Amy Gleichman @amygleichman.bsky.social · 20h

Thanks, Wendy!!

2

Amy Gleichman @amygleichman.bsky.social · 21h

And finally, a couple of virally-labeled astrocytes, because they are just so pretty. Red is a cortical astrocyte, green is a white matter astrocyte.

Left, red: a bushy, mostly spherical astrocyte in the mouse cortex
Right, green: a more elongated astrocyte in the mouse white matter

6

Amy Gleichman @amygleichman.bsky.social · 21h

I started my own lab about 6 months ago at Ohio State where we’re continuing to look at ways to manipulate astrocyte biology to improve brain repair. We’re also generating new viral tools along the way, for use in research and hopefully in gene therapies for patients down the line.

1 1 4

Amy Gleichman @amygleichman.bsky.social · 21h

Take-home message: astrocytes can respond in nuanced ways even to very similar injuries, and those nuances can be leveraged for interventions. Huge thank you to my postdoc mentor, Tom Carmichael, as well as our amazing collaborators Michael Sofroniew, Riki Kawaguchi, and Elle Rathbun.

1

Amy Gleichman @amygleichman.bsky.social · 21h

Looks like yes! Overexpression of Lamc1 in white matter astrocytes led to a smaller fibrotic scar and axotomized region as well as behavioral improvements. This also changed the immune cells entering the area, with a huge increase in Tregs. Overall, Lamc1 in white matter astrocytes improved repair.

1 1

Amy Gleichman @amygleichman.bsky.social · 21h

We made a lentivirus to overexpress Lamc1 in astrocytes and injected it in the white matter, and saw an increase in vascular remodeling specifically of those larger-caliber vessels. These are kind of weird vessels to have in white matter, which is more capillary-heavy. Are they a good thing?

1 1

Amy Gleichman @amygleichman.bsky.social · 21h

So it looks like Lamc1 is an endogenous mechanism by which cortical astrocytes improve repair after stroke, and it’s acting specifically to increase remodeling of arterioles and venules. Can we leverage this to improve repair in white matter stroke, where this mechanism doesn’t usually turn on?

1

Amy Gleichman @amygleichman.bsky.social · 21h

Surprisingly, we saw a pretty specific decrease in remodeling of arterioles and venules, but the capillary bed was unchanged. These vessels were all intact; knocking out Lamc1 didn’t affect blood-brain barrier permeability.

1 1

Amy Gleichman @amygleichman.bsky.social · 21h

Using a variety of metrics, we identified a pro-angiogenic gene (Lamc1) upregulated in cortical astrocytes near the stroke but not white matter astrocytes. We developed a dual-virus CRISPR system to knock it out in astrocytes in the cortex, and found a decrease in vascular remodeling post-stroke.

1 1

Amy Gleichman @amygleichman.bsky.social · 21h

Vascular remodeling and angiogenesis after a cortical stroke improve brain repair. We’ve known astrocytes in the cortex can help this process (see great work from @m-r-williamson.bsky.social and Theresa Jones), but it’s less clear what’s going on in white matter.

1

Amy Gleichman @amygleichman.bsky.social · 21h

While a lot of responses were shared between the cortical stroke and white matter stroke astrocytes, there were also some really intriguing differences. Top among those: cortical astrocytes were predicted to increase post-stroke vascular remodeling, while white matter astrocytes were not.

1 1

Amy Gleichman @amygleichman.bsky.social · 21h

But we didn’t see a correlation when we compared this module to astrocytes in other conditions, like aging or models of Alzheimer’s or Huntington’s disease. This module seems to be generalizable to reactive astrocytes within brain injury and inflammation, but not to all reactive astrocytes.

1

Amy Gleichman @amygleichman.bsky.social · 21h

The genes in this module – also heavily immune-related – show similar changes in other datasets where astrocytes are responding to injury and/or inflammation: spinal cord injury, cortical stab wound, systemic inflammation, other stroke datasets.

1 2

Amy Gleichman @amygleichman.bsky.social · 21h

There are a lot of similarities between the two: the most reactive astrocytes in both stroke models are heavily involved in immune responses. Using network analysis, we found a module of genes that particularly relates to the level of reactivity, regardless of stroke model.

1 1

Amy Gleichman @amygleichman.bsky.social · 21h

We defined zones of reactive astrocytes in mouse models both a large vessel cortical stroke and white matter stroke, using a lot of phenotypic and morphologic analyses, then used those zones for a transcriptomic analysis.

1 1

Amy Gleichman @amygleichman.bsky.social · 21h

Astrocytes in the white matter are pretty different from astrocytes in the gray matter. So we also wanted to include that layer of complexity – do white matter and gray matter astrocytes respond differently to stroke?

1 2

Amy Gleichman @amygleichman.bsky.social · 21h

We’re interested in both large-vessel strokes as well as small strokes that happen in the white matter tracts of the brain, which are clinically distinct forms of stroke. Small lacunar infarcts in the white matter are one of the underlying pathologies of vascular dementia.

1 1

Amy Gleichman @amygleichman.bsky.social · 21h

Long story slightly longer: Astrocytes react strongly to any kind of injury, like stroke. We wanted to understand more about the range of reactions – how are astrocytes right next to the stroke responding, and how much do those responses change as you get further away from the injury?

1 1

Amy Gleichman @amygleichman.bsky.social · 21h

Thrilled to share this work from my postdoc with Tom Carmichael, available online @ Neuron! Long story short: we find even more evidence that all reactive astrocytes are not equal, and we can take advantage of those differences to improve repair after stroke.
www.sciencedirect.com/science/arti...

Regionally mapped astrocytic responses to cortical and white matter stroke show differential roles in astrocyte-induced vascular remodeling

Stroke is a major cause of disability. Astrocytes respond to stroke in a gradated manner, but details of that response and its consequences for tissue…

www.sciencedirect.com

4 16 45

Reposted by Amy Gleichman

Travis Faust @travisfaust.bsky.social · 29d

Thrilled to share our new paper @cp-cell.bsky.social:
“Microglia–astrocyte crosstalk regulates synapse remodeling via Wnt signaling.”

This work demonstrates the necessity of glia–glia communication and coordination during synapse remodeling.

🔗 www.cell.com/cell/fulltex...

Faust et al., Cell 2025

11 25 66

Reposted by Amy Gleichman

Steven Sloan @sloanlab.bsky.social · Jun 30

I've been really hoping to see more manuscript threads here on 🦋, so here comes one!!! This is brand new work from the lab that took us in very unexpected directions and to exciting findings led by the amazing @emily-hill.bsky.social. Preprint here www.biorxiv.org/content/10.1...
and 🧵below:

2 10 24

Amy Gleichman @amygleichman.bsky.social · May 2

Thanks, Ashley!!

1