Biology subjects

Carretero-Guillen, A.

Publications and source records attributed to Carretero-Guillen, A..

3 recordsLinked to original sources

bioRxiv2026

Analysis of Long-Term Neuronal Dynamics via Ordinal Pattern Quantifiers Following Traumatic Brain Injury and Pharmacological Modulation

Traumatic brain injury (TBI) profoundly disrupts hippocampal network dynamics, triggering persistent alterations in oscillatory activity that underlie cognitive deficits and increased susceptibility to post-traumatic epilepsy. Characterizing these alterations quantitatively remains challenging: the resulting signals are nonlinear, non-stationary, and exhibit complex multiscale structure that conventional spectral metrics fail to resolve. Ordinal-pattern information-theoretic quantifiers offer a principled, model-free alternative for probing such dynamics. In this work we apply permutation entropy (PE), statistical complexity (SC), Fisher information (FI), and permutation Lempel-Ziv complexity (PLZC) to hippocampal local field potentials (LFPs) recorded over 21 days in a rodent controlled cortical impact model of TBI, across five experimental groups under distinct pharmacological conditions. Embedding signal trajectories in the SC-PE, FI-PE, and PLZC-PE information planes reveals group- and time-dependent dynamical signatures in the theta (4-8 Hz) and high-frequency oscillation (80-200 Hz) bands, exposing state transitions invisible to spectral analysis. Unsupervised dimensionality reduction (UMAP) combined with HDBSCAN clustering further delineates distinct regions of dynamical state space associated with injury progression and pharmacological modulation. We additionally applied the Ordinal Modulation Index (OMI), an ordinal-based measure of theta-HFO cross-frequency coupling, which captures treatment-dependent reorganization of phase-amplitude coordination. These results establish ordinal-pattern analysis as a sensitive and interpretable framework for tracking the nonlinear reorganization of hippocampal dynamics following TBI.

neuroscience↗

bioRxiv2021

Microglial phagocytosis dysfunction during stroke is prevented by rapamycin

Microglial phagocytosis is rapidly emerging as a therapeutic target in neurodegenerative and neurological disorders. An efficient removal of cellular debris is necessary to prevent buildup damage of neighbor neurons and the development of an inflammatory response. As the brain professional phagocytes, microglia are equipped with an array of mechanisms that enable them to recognize and degrade several types of cargo, including neurons undergoing apoptotic cell death. While microglia are very competent phagocytes of apoptotic cells under physiological conditions, here we report their dysfunction in mouse and monkey (Macaca fascicularis and Callithrix jacchus) models of stroke by transient occlusion of the medial cerebral artery (tMCAo). The impairment of both engulfment and degradation was related to energy depletion triggered by oxygen and nutrients deprivation (OND), which led to reduced process motility, lysosomal depletion, and the induction of a protective autophagy response in microglia. Basal autophagy, which is in charge of removing and recycling intracellular elements, was critical to maintain microglial physiology, including survival and phagocytosis, as we determined both in vivo and in vitro using knock-out models of autophagy genes and the autophagy inhibitor MRT68921. Notably, the autophagy inducer rapamycin partially prevented the phagocytosis impairment induced by tMCAo in vivo but not by OND in vitro. These results suggest a more complex role of microglia in stroke than previously acknowledged, classically related to the inflammatory response. In contrast, here we demonstrate the impairment of apoptotic cell phagocytosis, a microglial function critical for brain recovery. We propose that phagocytosis is a therapeutic target yet to be explored and provide evidence that it can be modulated in vivo using rapamycin, setting the stage for future therapies for stroke patients.

neuroscience↗

bioRxiv2020

Immediate and long-term effects of transcranial direct-current stimulation in the mouse primary somatosensory cortex

Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation technique consisting in the application of weak electric currents on the scalp. Although previous studies have demonstrated the clinical value of tDCS for modulating sensory, motor, and cognitive functions, there are still huge gaps in the knowledge of the underlying physiological mechanisms. To define the immediate impact as well as the after-effects of tDCS on sensory processing, we first performed electrophysiological recordings in primary somatosensory cortex (S1) of alert mice during and after administration of S1-tDCS, and followed up with immunohistochemical analysis of the stimulated brain regions. During the application of cathodal and anodal transcranial currents we observed polarity-specific bidirectional changes in the N1 component of the sensory-evoked potentials (SEPs) and associated gamma oscillations. Regarding the long-term effects observed after 20 min of tDCS, cathodal stimulation produced significant after-effects including a decreased SEP amplitude for up to 30 min, a power reduction in the 20-80 Hz range and a decrease in gamma event related synchronization (ERS). In contrast, no significant long-term changes in SEP amplitude or power analysis were observed after anodal stimulation except for a significant increase in gamma ERS after tDCS cessation. The polarity-specific differences of these long-term effects were corroborated by immunohistochemical analysis, which revealed an unbalance of GAD 65-67 immunoreactivity between the stimulated vs. non-stimulated S1 region only after cathodal tDCS. These results highlight the differences between immediate and long-term effects of tDCS, as well as the asymmetric long-term changes induced by anodal and cathodal stimulation. Significance StatementHere we provide a first glimpse at the immediate and long-term impact of tDCS on neural processing in alert animals. The obtained results highlight the complexity of tDCS-associated effects, which include both bidirectional as well as asymmetrical modulation depending on the polarity of the stimulation. This asymmetry suggests the implication of different mechanisms underlying the long-term effects induced by anodal and cathodal transcranial currents. Identifying and defining these effects and its associated mechanisms is crucial to help design effective protocols for clinical applications.

neuroscience↗