Biology subjects

Blanco-Suarez, E.

Publications and source records attributed to Blanco-Suarez, E..

4 recordsLinked to original sources

bioRxiv2026

Astrocytic chordin-like 1 (Chrdl1) is re-engaged early after ischemic stroke to regulate region-dependent GluA2 levels and neuronal vulnerability

Neuronal vulnerability to ischemic stroke varies markedly across brain regions, yet the mechanisms underlying this selective susceptibility remain poorly understood. Here, we show that the developmental astrocytic protein Chordin-like 1 (Chrdl1) is repurposed after ischemic injury to regulate neuronal vulnerability. Chrdl1 expression stabilizes GluA2-containing AMPA receptors, limits delayed apoptotic neuronal death, and preserves hippocampal function early after focal ischemic stroke, whereas sustained Chrdl1 expression does not improve long-term recovery. These findings identify an unexpected neuroprotective role for Chrdl1 during acute ischemia that contrasts with its previously described function as a limiter of synaptic plasticity during recovery. Our work reveals that developmental astrocyte-derived signaling can be redeployed after brain injury, with distinct functions depending on the stage of stroke and region-dependent endogenous expression that together determine whether a conserved neuroprotective mechanism is engaged after ischemic stroke.

neuroscience↗

bioRxiv2024

Recovery after human bone marrow mesenchymal stem cells (hBM-MSCs)-derived extracellular vesicles (EVs) treatment in post-MCAO rats requires handling associated with repeated behavioral testing.

Rehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training in animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising in restoring brain damage and function in stroke models. Additionally, the non-invasive intranasal route allows EVs to reach the brain and target specific ischemic regions. Yet unclear is how handling might enhance recovery or influence other therapies such as EVs after stroke. We used the transient middle cerebral artery occlusion (MCAO) model of stroke in rats to assess how intensive handling alone, in the form of sensorimotor behavioral tests, or in combination with an intranasal multidose or single dose of EVs restored neurological function and ischemic damage. Handled rats were exposed to a battery of sensorimotor tests, including the modified Neurological Severity Score (mNSS), beam balance, corner, grid walking, forelimb placement, and cylinder tests, together with Magnetic Resonance Imaging (MRI) at 2, 7, 14, 21, and 28 days post-stroke (dps). Handled MCAO rats were also exposed to an intranasal multidose of EVs (8 doses in total across four weeks, each dose containing 0.8 x 109 EVs in 120 {micro}l) or a single dose of EVs (2.4 x 109 EVs in 200 {micro}l) at 2 dps. Non-handled rats were evaluated only by mNSS and MRI at 2, 28, and 56 dps and were treated with a single intranasal dose of EVs. Our results showed that handling animals after MCAO is necessary for EVs to work and that a single cumulative dose of EVs further improves the neurological function recovered during handling without affecting ischemic damage. These results show the importance of rehabilitation in combination with other treatments and highlight how intensive behavioral testing might influence functional recovery after stroke, especially when other treatments are also given.

neuroscience↗

bioRxiv2020

Activity-Dependent Modulation of Synapse-Regulating Genes in Astrocytes

Astrocytes regulate the formation and function of neuronal synapses via multiple signals, however, what controls regional and temporal expression of these signals during development is unknown. We determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually-evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expression of synapse-regulating genes and synaptic development are also altered when astrocyte signaling is blunted by diminishing calcium release from astrocyte stores. Single nucleus RNA sequencing identified groups of astrocytic genes regulated by neuronal and astrocyte activity, and a cassette of genes that show layer-specific enrichment. Thus, the development of cortical circuits requires coordinated signaling between astrocytes and neurons, identifying astrocytes as a target to manipulate in neurodevelopmental disorders.

neuroscience↗

bioRxiv2020

Astrocyte-secreted chordin-like 1 regulates spine density after ischemic stroke

Ischemic stroke occurs when the brain is deprived of blood flow, preventing cells from receiving nutrients necessary to perform basic vital functions. In the peri-infarct area neurons undergo an acute loss of dendritic spines along with morphological alterations, which ultimately modify synaptic plasticity and determine neuronal survival. Astrocytes have been shown to play protective or detrimental roles in neuronal survival post-stroke, depending on the specific stage, yet we lack a clear understanding of the underlying mechanisms triggered at these different time points. Recently chordin-like 1 (Chrdl1) was identified as an astrocyte-secreted protein that promotes synaptic maturation and limits experience-dependent plasticity in the mouse visual cortex, leading us to ask if Chrdl1 regulates spine density and recovery from stroke. Using photothrombosis to model ischemic stroke, we studied Chrdl1 KO mice during the acute and subacute phases post-stroke (1 and 7 days after injury, respectively) to assess the potential of Chrdl1 to regulate spine density, glial reactivity and injury volume, characteristics that are involved in functional recovery after ischemia. We find that the absence of Chrdl1 prevents ischemia-induced spine loss in the peri-infarct area, a feature that indicates an important role of astrocytes in recovery from ischemic stroke.

neuroscience↗