Biology subjects

Luna-Munguia, H.

Publications and source records attributed to Luna-Munguia, H..

6 recordsLinked to original sources

bioRxiv2026

Effects of medial septum low-frequency deep brain stimulation on pentylenetetrazol-induced seizures in rats

AbstractO_ST_ABSBackgroundC_ST_ABSInvasive neuromodulation may be used in patients if seizure medications fail and surgery is not an option. However, moderate success is achieved and improved paradigms are required. The medial septum has been considered a suitable target for the treatment of temporal lobe epilepsy due to its location and connectivity. ObjectiveTo assess the effect of medial septum low-frequency deep brain stimulation to inhibit pentylenetetrazole (PTZ)-induced seizures. MethodsMale Sprague-Dawley rats were stereotaxically implanted in the medial septum and left dorsal hippocampus one week prior to the experimental protocols. Then, the animals were assigned to three experimental groups: 1) 10 Hz + PTZ (n=3); 2) 5 Hz + PTZ (n=7); and 3) 5 Hz (n=7). The stimulation consisted of a 30 min train of biphasic square-wave pulses at a current of 150 {micro}A and a pulse duration of 1 ms. Rats were subjected to the experimental protocol every 24 h for seven consecutive days. ResultsSubjects exposed to the 10 Hz died after the first PTZ injection. The 5 Hz stimulation not only prevented the animals death, but also induced a protective effect against generalization. Surprisingly, in both 5 Hz groups, septal and hippocampal spike-wave-like discharges were detected (mainly integrated by theta oscillations). This phenomenon was correlated with the generalization avoidance. ConclusionsWhile this study is preclinical in nature, our findings underscore the potential of using low-frequency medial septum stimulation for future clinical applications. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/720729v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@53482org.highwire.dtl.DTLVardef@1ba5d7corg.highwire.dtl.DTLVardef@4f999aorg.highwire.dtl.DTLVardef@1ed6744_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Analysis of cortical dysplasias using b-tensor encoding diffusion MRI in an animal model

Cortical dysplasias are malformations of cortical development characterized by disorganization of the cyto- and myeloarchitecture of the neocortex. They are a common cause of epilepsy and their diagnosis through conventional imaging can often be challenging, hindering surgical treatments. Diffusion-weighted magnetic resonance imaging (dMRI) has the ability to infer tissue properties at the microscopic scale, making it a promising technique for detection of cortical dysplasias. This study aims to assess the microarchitecture of the cerebral cortex in a murine model of cortical dysplasia using diffusion-weighted magnetic resonance imaging (dMRI) acquired with b-tensor encoding. Pregnant Sprague-Dawley rats were administered either carmustine (BCNU) or saline solution on day 15 of gestation. Their offspring were imaged at 120 days of age using a 7 tesla scanner, acquiring diffusion-sensitive images with b-tensor encoding. Images were processed with Q-space trajectory imaging with positivity constraints (QTI+) to derive various metrics along a curvilinear coordinate system across the neocortex. After scanning, the brains were processed for immunofluorescence and histological examinations. Experimental animals exhibited a significant reduction of microscopic fractional anisotropy ({micro}FA) and anisotropic kurtosis (Ka) in the middle and lateral cortical layers compared to the control animals. Immunofluorescence and histological analysis showed decreased and dysorganized myelinated fibers, and an increase of glial processes in BCNU-treated animals. Given the applicability of b-tensor encoding in clinical scanners, this approach holds promise for improving detection of focal cortical dysplasias in patients with epilepsy.

neuroscience↗

bioRxiv2025

Assessing the degree of cortical dislamination through electrical pattern analysis

Focal cortical dysplasia (FCD) is a leading cause of pharmacoresistant epilepsy in pediatric populations, although its contribution to epileptogenesis remains incompletely understood. Recent findings indicate that hyperexcitability might stem from peripheral areas that are not dysplastic, rather than from the malformation itself. However, consid-ering the significant variability associated with these malformations, it remains challenging to clarify whether this degree of disorganization contributes to changes in activity. In this study, we used the carmustine-induced animal model to investigate how varying degrees of cortical malformation influence neural dynamics. Local field potentials (LFP) were recorded using a multielectrode array (MEA) during both spontaneous activity and external perturbation. We developed a novel metric to quantify spatial heterogeneity in signal organization and evaluated its association with excitation-inhibition (E/I) balance. Our results reveal that alterations such as the aperiodic exponent value and the sparcity of clustering in signal classification are related to the extent and distribution of cortical abnormalities, underscoring the functional relevance of cytoarchitectural variability. This work advances the understanding of FCD-related network dysfunction and introduces analytical approaches with potential translational value for neuroscience research and pre-surgical evaluation.

neuroscience↗

bioRxiv2024

Longitudinal Multi-Tensor Analysis of Neocortical Microstructure in an Animal Model of Cortical Dysplasia

The neocortex is a highly organized structure, with region-specific spatial patterns of cells and fibers constituting cyto- and myelo-architecture, respectively. These architectural features are modulated during neurodevelopment, aging, and disease. While invasive techniques have contributed significantly to our understanding of cortical patterning, the task remains challenging through non-invasive methods. Structural magnetic resonance imaging (MRI) has advanced to improve sensitivity in identifying cortical features, yet most methods focus on capturing macrostructural characteristics, often overlooking critical microscale components. Diffusion-weighted MRI (dMRI) offers an opportunity to extract quantitative information reflecting microstructural changes. Here we investigate how different dMRI modalities contribute to the detection of microstructural characteristics and whether per-bundle approaches can disentangle characteristics related to the orientational organization of the myelo- and cyto-architecture in an animal model of cortical dysplasia, a malformation of cortical development. We scanned 32 animals (n=16 experimental; n=16 control) at four different time points (30, 60, 120, and 150 post-natal days) using both structural and multi-shell diffusion-weighted MRI. All dMRI metrics were sampled using a 2D curvilinear system of coordinates as a common anatomical descriptor across animals. Per-bundle metrics were labeled according to their orientation with respect to the cortical surface, and analyzed separately. Experimental animals showed diffusion abnormalities of the tangential and radial fiber components in deeper cortical areas, consistent with histological findings of neuronal and fiber disorganization. The ability of dMRI to detect abnormalities in an animal model of cortical dysplasia is indicative of the clinical potential of advanced dMRI methods to study cortical microstructure in neurological disorders.

neuroscience↗

bioRxiv2023

Selective medial septum lesions in healthy rats induce longitudinal changes in microstructure of limbic regions, behavioral alterations, and increased susceptibility to status epilepticus

Septo-hippocampal pathway is crucial for physiological functions and is involved in epilepsy. Its clinical monitoring during epileptogenesis is complicated. We aim to evaluate tissue changes after lesioning the medial septum of normal rats and assess how the depletion of specific neuronal populations alters the animals behavior and susceptibility to establishing a pilocarpine-induced status epilepticus. A total of 64 young-adult male Sprague-Dawley rats were injected into the medial septum with vehicle or saporins (GAT1 or 192-IgG for GABAergic or cholinergic depletion, respectively; n=16 per group). Thirty-two animals were used for diffusion tensor imaging (DTI); they were scanned before surgery and 14 and 49 days post-injection. Fractional anisotropy and apparent diffusion coefficient were evaluated in the fimbria, dorsal hippocampus, ventral hippocampus, dorso-medial thalamus and amygdala. Between scans 2 and 3, animals were submitted to the elevated plus-maze, open-field test, rotarod test, Y-maze and water-maze. Timm, toluidine and Nissl staining were used to analyze tissue alterations. Twenty-four different animals received pilocarpine to evaluate the latency and severity of the status epilepticus two weeks after surgery. Eight animals were only used to evaluate the extent of neuronal damage inflicted on the medial septum one week after the molecular surgery. Progressive changes in DTI parameters in both the white and gray matter structures of the four evaluated groups were observed. Behaviorally, the GAT1-saporin injection impacted spatial memory formation, while 192-IgG-saporin triggered anxiety-like behaviors. Histologically, the GABAergic toxin also induced aberrant mossy fiber sprouting, tissue damage and neuronal death. Regarding the pilocarpine-induced status epilepticus, this agent provoked an increased mortality rate. Selective septo-hippocampal modulation impacts the integrity of limbic regions crucial for certain behavioral skills and could represent a precursor for epilepsy development. Significance statementThe medial septum is believed to be involved in epilepsy. However, whether and how defects in the integrity of each neuronal subpopulation conforming this structure affect gray and white matter structures remains unclear. Here we examine whether the injection of vehicle or partially-selective saporins into medial septum of normal rats play a role in the integrity of specific brain regions relevant to memory formation, anxiety-like behaviors, and susceptibility to status epilepticus induction and survival. We find that lesioning the medial septum GABAergic or cholinergic neurons can represent a precursor for behavioral deficits or epilepsy development. Therefore, these results strongly support the idea that modulation of medial septum can be a potential target to improve cognition or reduce seizure frequency.

neuroscience↗

bioRxiv2023

Differentiation of white matter histopathology using b-tensor encoding and machine learning

Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) is a non-invasive technique that is sensitive to microstructural geometry in neural tissue and is useful for the detection of neuropathology in research and clinical settings. Tensor valued diffusion encoding schemes (b-tensor) have been developed to enrich the microstructural data that can be obtained through DW-MRI. These advanced methods have proven to be more specific to microstructural properties than conventional DW-MRI acquisitions. Additionally, machine learning methods are particularly useful for the study of multidimensional data sets. In this work, we have tested the reach of b-tensor encoding data analyses with machine learning in different histopathological scenarios. We achieved this in three steps: 1) We induced different forms of white matter damage in rodent optic nerves. 2) We obtained ex-vivo DW-MRI with b-tensor encoding schemes and calculated quantitative metrics using Q-space Trajectory Imaging. 3) We used a machine learning model to identify the main contributing features and built a voxel-wise probabilistic classification map of histological damage. Our results show that this model is sensitive to characteristics of microstructural damage. In conclusion, b-tensor encoded DW-MRI analyzed with machine learning methods, have the potential to be further developed for the detection of histopathology and neurodegeneration.

neuroscience↗