Research

The brain has an extraordinary ability to remodel and shape its circuits in response to the information that it receives, a phenomenon referred to as "plasticity". As the brain matures, plasticity decreases. Our goal is to understand how astrocytes, a specialized cell type in the brain, boost brain plasticity,  and harness their potential to repair neuronal connections, called synapses, during disease or after injury like a stroke.

We study the time- and region-specific astrocyte contributions to neuroprotection and synaptic restoration. To achieve this, we use in vivo and in vitro mouse models of ischemic stroke along with a diverse array of  biochemical techniques, molecular biology, high-resolution imaging, and behavioral tests. 

Through our research, we aim to harness the therapeutic potential of astrocytic proteins to enhance protection and facilitate recovery from various injury and disease conditions. 

Scroll down to learn more about our ongoing projects.

The Blanco-Suárez Lab is funded by the American Heart Association, the Chan Zuckerberg Initiative (CZI), and the Neurovascular Center of the Farber Institute for Neuroscience at Thomas Jefferson University.

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Image of a spatial transcriptomics experiment using MERFISH on a coronal section of a mouse brain 7 days after focal stroke in the motor cortex. Credit: Dr. Blanco-Suárez, in collaboration with Dr. Schafer's lab (UMass).

Time- and Region-Dependent Astrocyte Response to Stroke

Using in vitro and in vivo models of ischemic stroke, we aim to identify transcriptional changes in astrocytes that depend on time (i.e. timepoint after stroke onset) and location (brain region affected, and proximity to the core of the stroke). These studies are poised to unveil molecules and astrocyte-mediated pathways that might have been overlooked, yet hold potential for regulating post-stroke neuronal plasticity and facilitating functional recovery .

Synaptic staining of postsynaptic GluA2 and presynaptic VGluT1 in the motor cortex of a male mouse. Circled in white, co-localization of GluA2 and VGluT1 (synapse). Credit: Dr. Elena Blanco-Suárez.

Region-Dependent Astrocytic Regulation of Excitatory Synapses after Injury

In the context of chronic diseases and acute injury, the distribution and composition of neuronal receptors at excitatory synapses often undergo changes, sometimes favoring molecular cascades that ultimately lead to neuronal death. This phenomenon varies depending on the brain region affected. 

Our research revealed that astrocytes play a crucial role at regulating the composition of these neuronal receptors at excitatory synapses during healthy brain development and maturation in a region-dependent manner. Our goal is to identify astrocytic proteins, which we term "resilience factors", that may mitigate early impairments in these receptors. By doing so, we aim to slow down or even halt the progression of injury and disease.

Dendrites from two different neurons of a male mouse brain showing spines (red arrows) before and 1 day post-stroke (dps). Image taken with a high-resolution confocal microscope. Credit: Dr. Elena Blanco-Suárez.

Astrocyte-Mediated Structural Plasticity in Pathological Conditions

In many neurodegenerative diseases, neurons typically experience the loss of dendritic spines, the structures where synapses are located. This loss ultimately leads to neuronal death due to their inability to fulfill their function. However, in certain injury and disease conditions, increased plasticity may facilitate the formation of new dendritic spines and synapses, thereby promoting recovery. 

Our objective is to manipulate astrocytic genes and proteins to extend or re-open plasticity time windows, particularly in later stages of life and following injury. Our previous studies have shown promising results. We found that elimination of Chordin-like 1, an important astrocytic protein, has been associated with the preservation of dendritic spines after ischemic stroke. This preservation creates an optimal environment for neurons to restore lost synapses, ultimately enhancing functional recovery.

Diagram of how PM-tethered and cytosolic BioID2 will biotinylate proteins in a proximity-dependent manner over ~10 nm. (Adapted from Soto et al., 2023, PMID: 38062165).

Astrocyte-Neuron Subproteomes for Stroke Therapies

With this pilot study, we aim to identify astrocyte-neuron subproteomes in a pre-clinical model of permanent stroke, and find biomarkers and therapeutic strategies to stall neurodegeneration and cognitive decline in the long term. 

This project is conducted in collaboration with Dr. Baljit Khakh in University of California, Los Angeles.

Confocal image of EVs (labelled in red with ExoGlow) internalized by cells (nuclei labelled with DAPI) located in the peri-infarct area of an adult rat brain 48h after stroke. Credit: Dr. Yolanda Gómez-Gálvez.

Stem Cell-Derived Extracellular Vesicles for Stroke Treatment

Bone-marrow mesenchymal stem cells have shown promise in improving motor symptoms when administered after stroke, as evidenced by several pre-clinical and clinical studies. This beneficial effect is believed to be mediated by the release of extracellular vesicles (EVs),  which contain factors that promote regeneration and repair of the nervous system.

In this study, we aim to investigate the adjuvant factors that contribute to the efficiency of EV-based treatment in a rat model of stroke. 

This project is conducted in collaboration with Dr. Lorraine Iacovitti's lab at Thomas Jefferson University.