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Encinas-Perez, J. M.

Publications and source records attributed to Encinas-Perez, J. M..

2 recordsLinked to original sources

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↗

HB-EGF and zinc activate EGFR to induce reactive neural stem cells in the mouse hippocampus after seizures

Hippocampal seizures mimicking mesial temporal lobe epilepsy (MTLE) cause a profound disruption of the adult neurogenic niche in mice. Seizures provoke neural stem cells to switch to a reactive phenotype (reactive-neural stem cells, React-NSCs)) characterized by multibranched hypertrophic morphology, massive activation to enter mitosis, symmetric division and final differentiation into reactive astrocytes. As a result, neurogenesis is chronically impaired. Here we, using a mouse model of MTLE, show that the epidermal growth factor receptor (EGFR) signalization pathway is key for the induction of React-NSCs and that its inhibition exerts a beneficial effect on the neurogenic niche. We show that during the initial days after the induction of seizures by a single intrahippocampal injection of kainic acid, a strong release of zinc and heparin-binding epidermal growth factor, both activators of the EGFR signalization pathway in neural stem cells, is produced. Administration of the EGFR inhibitor gefitinib, a chemotherapeutic in clinical phase IV, prevents the induction of React-NSCs and preserves neurogenesis. SignificanceIn mouse models of MTLE-HS, seizures cause a profound disruption of the hippocampal neurogenic niche and neurogenesis results chronically impaired, in agreement with what occurs in the human MTLE-HS hippocampus. Thus, the normal cognitive functions associated with neurogenesis are altered, but also the endogenous regenerative capacity that could compensate the high rate of neurons in the granule cell layer of the dentate gyrus. We provide here for the first time a molecular mechanism (the EGFR transduction pathway) regulating the induction of React-NSCs.

neuroscience↗