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Objectives Oral lichen planus ( OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high-affinity histamine H4 receptors (H4Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T-cell cytokines. Materials and Methods Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real-time polymerase chain reaction of tissue samples and cytokine-stimulated cultured SCC-25 and primary human oral keratinocytes. Results H4R immunoreactivity was weak in OLP and characterized by mast cell ( MC) hyperplasia and degranulation. In contrast to controls, H4R immunostaining and MC counts were negatively correlated in OLP ( P = 0.003). H4R agonist at nanomolar levels led to a rapid internalization of H4Rs, whereas high histamine concentration and interferon- γ decreased HRH4-gene transcripts. Conclusion Healthy oral epithelial cells are equipped with H4R, which displays a uniform staining pattern in a MC-independent fashion. In contrast, in OLP, increased numbers of activated MCs associate with increasing loss of epithelial H4R. Cell culture experiments suggest a rapid H4R stimulation-dependent receptor internalization and a slow cytokine-driven decrease in H4R synthesis. H4R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF)-alpha is a pro-inflammatory cytokine and crucial mediator in many aspects of immunity. Although several studies have shown that recurrent aphthous ulcers (RAU) can be prevented by treatment that prevents the synthesis of endogenous TNF-alpha little is known about the location and distribution of TNF-alpha-expressing cells at disease sites. The aim of the present work is, therefore, to investigate TNF-alpha and its cellular distribution in RAU lesions compared with those in induced oral traumatic ulcers (TUs). Twelve biopsies of RAU lesions of oral mucosa were obtained from 12 patients with RAU. They were compared to a control group consisting of ten samples of induced TUs. All samples were analyzed for TNF-alpha expression by using monoclonal mouse anti-human TNF-alpha antibody in avidin-biotin-peroxidase complex (ABC) staining. Results were quantified by a semi-automatic VIDAS image analysis system. TNF-alpha immunoreactivity was contained mainly in monocyte/macrophages and lymphocytes within the mononuclear inflammatory infiltrates. TNF-alpha was often seen in mast cells and vascular endothelial cells in connective tissue lateral to the inflammatory infiltrates. Interestingly, 32%-60% of the mononuclear cells were found to be TNF-alpha immunoreactive in RAU lesions. TNF-alpha containing cells were more numerous in aphthae (188+/-46 cells/0.2 mm2) compared with controls (52+/-14 cells/0.2 mm2, P<0.001). These findings suggest that RAU lesions are characterized by high expression of TNF-alpha. Because such expression occurred in the mononuclear inflammatory cells, mast cells and vascular endothelial cells, TNF-alpha, which is a major inflammatory mediator, may contribute to the activation and recruitment of leukocytes that are found in RAU lesions. [ABSTRACT FROM AUTHOR]

Specimens from nonkeratinized oral mucosa were obtained from diseased and clinically healthy mucosa from 7 patients with minor recurrent aphthous ulcers. The innervation of the specimens was visualized using antibodies to neuron- specific intermediate cytoskeletal neurofilament fiber, the cytoplasmic protein gene product 9.5 and a 38 kDa integral membrane protein of synaptic vesicles applied in avidin-biotin-peroxidase staining. Mapping with these 3 antibodies revealed dense and basically similar pattern of innervation in the specimens of the clinically healthy oral mucosa. In recurrent aphthous ulcers, all 3 general markers disclosed peripheral nerve fibers also in the lesions, apart from the necrotic area, among the inflammatory cells without signs of retraction from the diseased area. Synaptophysin staining suggested that these peripheral nerve fibers in the inflammatory areas still contained synaptic vesicles. Accordingly, they were shown to contain substance P and calcitonin gene-related peptide. which are known to be relased upon stimulation of the nerve and can exert potent paracrine actions, possibly on the local inflammatory cells as suggested by a close spatial relationship between neuropeptide-containing nerves and inflammatory cells. [ABSTRACT FROM AUTHOR]

Previous studies on the frequency of mast cells (MCs) in recurrent aphthous ulcers (RAU) have yielded conflicting results. Monoclonal antibodies specific for tryptase (AAI) and anti-IgE (polyclonal antibody) were used to identify density and distribution of MCs in an immunohistochemical study of RAU (n= 15). induced oral traumatic ulcers (TUs) (n=9), and control clinically healthy oral mucosa (n = 15). Results were quantified by means of a VIDAS image analyzer. In all sections studied, IgE-positive cells showed similar frequency and distribution to tryptase-positive MCs. In RAU lesions, numerous tryptase-positive MCs were found in the sub-epithelial lamina propria, but MC numbers in the epithelium were low and present only in some RAU biopsies. MCs were also more numerous in RAU-inflammatory infiltrates (118 ± 31 cells/mm²) than those seen in TU-inflammatory infiltrates (75 ± 18 cells mm². P<0.001). MC activation/degranulation, as judged by diffuse extracellular tryptase staining, was a common feature within RAU-inflammatory infiltrates and at RAU-inflammatory in- filtrates-connective tissue interfaces, which were often associated with connective tissue disruption. MC counts in the RAU connective tissue, lateral to the inflammatory infiltrates, were significantly greater than in the connective tissue of TUs and of control biopsies (l24±36 vs 73± 13 vs 69±21 cells/mm² respectively: P&lt0.001). Overall, MCs were significantly increased in aphthae (116±26 cells/mm²) compared with TU lesions (72±11 cells/mm², P<0.001) and controls (71±16 cells/mm. P<0.001). In conclusion, MC numbers are increased in a typical topographical pattern, and the local MCs show signs of activation:degranulation suggesting active involvement of this cell type in RAU pathogenesis. [ABSTRACT FROM AUTHOR]

The factor XIIIa-positive (FXIIIa+) cell is a potent antigen-presenting cell, which has been described as increasing in numbers in various chronic inflammatory conditions. The purpose of this study was to investigate the distribution and frequency of FXIIIa+ cells in acute recurrent aphthous ulcer (RAU) lesions compared with induced traumatic ulcer (TU) lesions and with clinically healthy oral mucosa. Samples were labeled with polyclonal rabbit anti-human FXIIIa antibodies in avidin-biotin-peroxidase complex (ABC) staining. Most of the FXIIIa-immunoreactive cells in TUs and normal mucosa were spindle-shaped, whereas a relatively large, dendritic-like cell was predominant in RAU lesions. FXIIIa+ cells were quite frequent within mononuclear cell-rich inflammatory cell infiltrates and in perivascular areas in RAU lesions. In contrast, FXIIIa+ cells were not found in mucosal epithelium or in the neutrophil-rich areas. RAU mononuclear cell-rich inflammatory cell infiltrates appeared to have greater numbers of positively stained cells than the TU-inflammatory cell infiltrates (199 +/- 67 vs 110 +/- 31 cells/mm2, P < 0.001). Overall, FXIIIa+ dendrocytes were increased in numbers, and apparently also in size, in RAU lesions (274 +/- 68/mm2) as compared to controls (177 +/- 74/mm2, P < 0.01), and to TU lesions (183 +/- 50 mm2, P < 0.01). Interestingly, relatively high numbers of FXIIIa+ dendrocytes were also found in deep connective tissue in RAU sections compared with TUs (281 +/- 80 vs 166 +/- 57, P < 0.01). The characteristic changes in the size and shape of individual FXIIIa+ cells, their typical distribution and increase in frequency in RAU lesions indicate active involvement in the local pathogenic mechanisms. Localization to perivascular areas/inflammatory cell infiltrates would be compatible with a role in antigen presentation. [ABSTRACT FROM AUTHOR]

Human neutrophil-type (MMP-8) and fibroblast-type (MMP-1) interstitial collagenase, and their inhibition by tetracyclines in saliva from patients with recurrent aphthous ulcers (RAU) or aphthae, were studied by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and enzymological analyses. In the salivary specimens obtained from patients with aphthae, collagenase was found in endogenously active form and was predominantly of MMP-8 type. Topical rinsing treatment with chlortetracycline (Aureomycin) alleviated the discomfort caused by the lesions but did not reduce salivary collagenase amounts; however in vitro, doxycycline inhibited salivary collagenase totally. [ABSTRACT FROM AUTHOR]

The topographical distribution and relation to mast cells of PGP 9.5 (protein gene product 9.5. a major cytoplasmic neuron-specific protein with ubiquitin C-terminal hydrolase activity) and neurolilament (intermediate neuron-specific cytoskeletal filaments) in normal human buccal mucosa was studied in five healthy volunteers. Morphometric analysis disclosed the densest innervation to be in the middle layers of the lamina propria, with a mean number of 5.9-6.1 PGP 9.5 and/or neurofilament-immunoreactive nerve fiber profiles per one mm[sup2]. In contrast, the mean mast cell number decreased from 110/mm[sup2] to 46/mm[sup2] from superficial to deep lamina propria. being 69-72/mm[sup2] in the most densely innervated middle layers. Only 16-17% of all fiber profiles contained substance P and 51-54% calcitonin gene-related peptide (CGRP). Finally, analysis of the spatial relationship between nerve fiber profiles and mast cells in a double staining procedure disclosed no preferential neuron-effector associations. All these findings suggest that such a relationship does not exist between peripheral nerves and mast cells in normal buccal mucosa. [ABSTRACT FROM AUTHOR]

When activated under physiologic or pathologic conditions leukocytes adhere to one another or to other cell types. Adhesion receptors mediate these interactions. In the study reported here, the distribution of the adhesion receptors LFA-1 (CD11a/CD18), ICAM-1 (CD54), CD2 and LFA-3 (CD58) in recurrent oral ulcers (ROU) were studied. Nine tissue specimens from five female patients (mean age 33 yr, age range 21-40 yr) with ROU were studied using the avidin-biotinperoxidase complex (ABC) method. The main mononuclear cell infiltrations were in lamina propria (LP) and the epithelium next to the basement membrane (BM), laterally to the ulcers. In this area, ICAM-1 was strongly expressed in capillaries and in postcapillary venules. LFA-1, LFA-3 and CD2 were expressed in 654±11%, 704±16% and 804±1%, respectively, of all mononuclear cells. The findings indicate that LFA-1/ICAM-1 and CD2/LFA-3 interactions may play roles in cell to cell adhesion events in ROU. [ABSTRACT FROM AUTHOR]

Objective: To test a hypothesis that acutely regulated plasma microRNAs (miRNAs) can serve as prognostic biomarkers for the development of post-traumatic epilepsy (PTE)., Methods: Adult male Sprague-Dawley rats (n = 245) were randomized to lateral fluid-percussion-induced traumatic brain injury (TBI) or sham operation at three study sites (Finland, Australia, United States). Video-electroencephalography (vEEG) was performed on the seventh post-injury month to detect spontaneous seizures. Tail vein plasma collected 48 h after TBI for miRNA analysis was available from 209 vEEG monitored animals (45 sham, 164 TBI [32 with epilepsy]). Based on small RNA sequencing and previous data, the seven most promising brain enriched miRNAs (miR-183-5p, miR-323-3p, miR-434-3p, miR-9a-3p, miR-124-3p, miR-132-3p, and miR-212-3p) were validated by droplet digital polymerase chain reaction (ddPCR)., Results: All seven plasma miRNAs differentiated between TBI and sham-operated rats. None of the seven miRNAs differentiated TBI rats that did and did not develop epilepsy (p > .05), or rats with ≥3 vs <3 seizures in a month (p > .05). However, miR-212-3p differentiated rats that developed epilepsy with seizure clusters (i.e., ≥3 seizures within 24 h) from those without seizure clusters (.34 ± .14 vs .60 ± .34, adj. p < .05) with an area under the curve (AUC) of .81 (95% confidence interval [CI] .65-.97, p < .01, 64% sensitivity, 95% specificity). Lack of elevation in miR-212-3p also differentiated rats that developed epilepsy with seizure clusters from all other TBI rats (n = 146, .34 ± .14 vs .55 ± .31, p < .01) with an AUC of .74 (95% CI .61-.87, p < .01, 82% sensitivity, 62% specificity). Glmnet analysis identified a combination of miR-212-3p and miR-132-3p as an optimal set to differentiate TBI rats with vs without seizure clusters (cross-validated AUC .75, 95% CI .47-.92, p < .05)., Significance: miR-212-3p alone or in combination with miR-132-3p shows promise as a translational prognostic biomarker for the development of severe PTE with seizure clusters., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Integrating datasets from multiple sites and scanners can increase statistical power for neuroimaging studies but can also introduce significant inter-site confounds. We evaluated the effectiveness of ComBat, an empirical Bayes approach, to combine longitudinal preclinical MRI data acquired at 4.7 or 9.4 T at two different sites in Australia. Male Sprague Dawley rats underwent MRI on Days 2, 9, 28, and 150 following moderate/severe traumatic brain injury (TBI) or sham injury as part of Project 1 of the NIH/NINDS-funded Centre Without Walls EpiBioS4Rx project. Diffusion-weighted and multiple-gradient-echo images were acquired, and outcomes included QSM, FA, and ADC. Acute injury measures including apnea and self-righting reflex were consistent between sites. Mixed-effect analysis of ipsilateral and contralateral corpus callosum (CC) summary values revealed a significant effect of site on FA and ADC values, which was removed following ComBat harmonization. Bland-Altman plots for each metric showed reduced variability across sites following ComBat harmonization, including for QSM, despite appearing to be largely unaffected by inter-site differences and no effect of site observed. Following harmonization, the combined inter-site data revealed significant differences in the imaging metrics consistent with previously reported outcomes. TBI resulted in significantly reduced FA and increased susceptibility in the ipsilateral CC, and significantly reduced FA in the contralateral CC compared with sham-injured rats. Additionally, TBI rats also exhibited a reversal in ipsilateral CC ADC values over time with significantly reduced ADC at Day 9, followed by increased ADC 150 days after injury. Our findings demonstrate the need for harmonizing multi-site preclinical MRI data and show that this can be successfully achieved using ComBat while preserving phenotypical changes due to TBI., (© 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Timely relief of edema and clearance of waste products, as well as promotion of anti-inflammatory immune responses, reduce ischemic stroke pathology, and attenuate harmful long-term effects post-stroke. The discovery of an extensive and functional lymphatic vessel system in the outermost meningeal layer, dura mater, has opened up new possibilities to facilitate post-stroke recovery by inducing dural lymphatic vessel (dLV) growth via a single injection of a vector encoding vascular endothelial growth factor C (VEGF-C). In the present study, we aimed to improve post-stroke outcomes by inducing dLV growth in mice. We injected mice with a single intracerebroventricular dose of adeno-associated viral particles encoding VEGF-C before subjecting them to transient middle cerebral artery occlusion (tMCAo). Behavioral testing, Gadolinium (Gd) contrast agent-enhanced magnetic resonance imaging (MRI), and immunohistochemical analysis were performed to define the impact of VEGF-C on the post-stroke outcome. VEGF-C improved stroke-induced behavioral deficits, such as gait disturbances and neurological deficits, ameliorated post-stroke inflammation, and enhanced an alternative glial immune response. Importantly, VEGF-C treatment increased the drainage of brain interstitial fluid (ISF) and cerebrospinal fluid (CSF), as shown by Gd-enhanced MRI. These outcomes were closely associated with an increase in the growth of dLVs around the region where we observed increased vefgc mRNA expression within the brain, including the olfactory bulb, cortex, and cerebellum. Strikingly, VEGF-C-treated ischemic mice exhibited a faster and stronger Gd-signal accumulation in ischemic core area and an enhanced fluid outflow via the cribriform plate. In conclusion, the VEGF-C-induced dLV growth improved the overall outcome post-stroke, indicating that VEGF-C has potential to be included in the treatment strategies of post-ischemic stroke. However, to maximize the therapeutic potential of VEGF-C treatment, further studies on the impact of an enhanced dural lymphatic system at clinically relevant time points are essential., (© 2024. The Author(s).)

Objective: To assess the prevalence of brain abscesses as a confounding factor for the diagnosis of post-traumatic epilepsy (PTE) in a rat model of lateral fluid-percussion-induced (FPI) traumatic brain injury (TBI)., Methods: This retrospective study included 583 rats from 3 study cohorts collected over 2009-2022 in a single laboratory. The rats had undergone sham-operation or TBI using lateral FPI. Rats were implanted with epidural and/or intracerebral electrodes for electroencephalogram recordings. Brains were processed for histology to screen for abscess(es). In abscess cases, (a) unfolded cortical maps were constructed to assess the cortical location and area of the abscess, (b) the abscess tissue was Gram stained to determine the presence of gram-positive and gram-negative bacteria, and (c) immunostaining was performed to detect infiltrating neutrophils, T-lymphocytes, and glial cells as tissue biomarkers of inflammation. In vivo and/or ex vivo magnetic resonance images available from a subcohort of animals were reviewed to evaluate the presence of abscesses. Plasma samples available from a subcohort of rats were used for enzyme-linked immunosorbent assays to determine the levels of lipopolysaccharide (LPS) as a circulating biomarker for gram-negative bacteria., Results: Brain abscesses were detected in 2.6% (15/583) of the rats (6 sham, 9 TBI). In histology, brain abscesses were characterized as vascularized encapsulated lesions filled with neutrophils and surrounded by microglia/macrophages and astrocytes. The abscesses were mainly located under the screw electrodes, support screws, or craniectomy. Epilepsy was diagnosed in 60% (9/15) of rats with an abscess (4 sham, 5 TBI). Of these, 67% (6/9) had seizure clusters. The average seizure frequency in abscess cases was 0.436 ± 0.281 seizures/d. Plasma LPS levels were comparable between rats with and without abscesses (p > 0.05)., Significance: Although rare, a brain abscess is a potential confounding factor for epilepsy diagnosis in animal models of structural epilepsies following brain surgery and electrode implantation, particularly if seizures occur in sham-operated experimental controls and/or in clusters., Competing Interests: Declaration of competing interest The authors confirm that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: This study was undertaken to assess reproducibility of the epilepsy outcome and phenotype in a lateral fluid percussion model of posttraumatic epilepsy (PTE) across three study sites., Methods: A total of 525 adult male Sprague Dawley rats were randomized to lateral fluid percussion-induced brain injury (FPI) or sham operation. Of these, 264 were assigned to magnetic resonance imaging (MRI cohort, 43 sham, 221 traumatic brain injury [TBI]) and 261 to electrophysiological follow-up (EEG cohort, 41 sham, 220 TBI). A major effort was made to harmonize the rats, materials, equipment, procedures, and monitoring systems. On the 7th post-TBI month, rats were video-EEG monitored for epilepsy diagnosis., Results: A total of 245 rats were video-EEG phenotyped for epilepsy on the 7th postinjury month (121 in MRI cohort, 124 in EEG cohort). In the whole cohort (n = 245), the prevalence of PTE in rats with TBI was 22%, being 27% in the MRI and 18% in the EEG cohort (p > .05). Prevalence of PTE did not differ between the three study sites (p > .05). The average seizure frequency was .317 ± .725 seizures/day at University of Eastern Finland (UEF; Finland), .085 ± .067 at Monash University (Monash; Australia), and .299 ± .266 at University of California, Los Angeles (UCLA; USA; p < .01 as compared to Monash). The average seizure duration did not differ between UEF (104 ± 48 s), Monash (90 ± 33 s), and UCLA (105 ± 473 s; p > .05). Of the 219 seizures, 53% occurred as part of a seizure cluster (≥3 seizures/24 h; p >.05 between the study sites). Of the 209 seizures, 56% occurred during lights-on period and 44% during lights-off period (p > .05 between the study sites)., Significance: The PTE phenotype induced by lateral FPI is reproducible in a multicenter design. Our study supports the feasibility of performing preclinical multicenter trials in PTE to increase statistical power and experimental rigor to produce clinically translatable data to combat epileptogenesis after TBI., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Project 1 of the Preclinical Multicenter Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) consortium aims to identify preclinical biomarkers for antiepileptogenic therapies following traumatic brain injury (TBI). The international participating centers in Finland, Australia, and the United States have made a concerted effort to ensure protocol harmonization. Here, we evaluate the success of harmonization process by assessing the timing, coverage, and performance between the study sites., Method: We collected data on animal housing conditions, lateral fluid-percussion injury model production, postoperative care, mortality, post-TBI physiological monitoring, timing of blood sampling and quality, MR imaging timing and protocols, and duration of video-electroencephalography (EEG) follow-up using common data elements. Learning effect in harmonization was assessed by comparing procedural accuracy between the early and late stages of the project., Results: The animal housing conditions were comparable between the study sites but the postoperative care procedures varied. Impact pressure, duration of apnea, righting reflex, and acute mortality differed between the study sites (p < 0.001). The severity of TBI on D2 post TBI assessed using the composite neuroscore test was similar between the sites, but recovery of acute somato-motor deficits varied (p < 0.001). A total of 99% of rats included in the final cohort in UEF, 100% in Monash, and 79% in UCLA had blood samples taken at all time points. The timing of sampling differed on day (D)2 (p < 0.05) but not D9 (p > 0.05). Plasma quality was poor in 4% of the samples in UEF, 1% in Monash and 14% in UCLA. More than 97% of the final cohort were MR imaged at all timepoints in all study sites. The timing of imaging did not differ on D2 and D9 (p > 0.05), but varied at D30, 5 months, and ex vivo timepoints (p < 0.001). The percentage of rats that completed the monthly high-density video-EEG follow-up and the duration of video-EEG recording on the 7th post-injury month used for seizure detection for diagnosis of post-traumatic epilepsy differed between the sites (p < 0.001), yet the prevalence of PTE (UEF 21%, Monash 22%, UCLA 23%) was comparable between the sites (p > 0.05). A decrease in acute mortality and increase in plasma quality across time reflected a learning effect in the TBI production and blood sampling protocols., Significance: Our study is the first demonstration of the feasibility of protocol harmonization for performing powered preclinical multi-center trials for biomarker and therapy discovery of post-traumatic epilepsy., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Preclinical MRI studies have been utilized for the discovery of biomarkers that predict post-traumatic epilepsy (PTE). However, these single site studies often lack statistical power due to limited and homogeneous datasets. Therefore, multisite studies, such as the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx), are developed to create large, heterogeneous datasets that can lead to more statistically significant results. EpiBioS4Rx collects preclinical data internationally across sites, including the United States, Finland, and Australia. However, in doing so, there are robust normalization and harmonization processes that are required to obtain statistically significant and generalizable results. This work describes the tools and procedures used to harmonize multisite, multimodal preclinical imaging data acquired by EpiBioS4Rx. There were four main harmonization processes that were utilized, including file format harmonization, naming convention harmonization, image coordinate system harmonization, and diffusion tensor imaging (DTI) metrics harmonization. By using Python tools and bash scripts, the file formats, file names, and image coordinate systems are harmonized across all the sites. To harmonize DTI metrics, values are estimated for each voxel in an image to generate a histogram representing the whole image. Then, the Quantitative Imaging Toolkit (QIT) modules are utilized to scale the mode to a value of one and depict the subsequent harmonized histogram. The standardization of file formats, naming conventions, coordinate systems, and DTI metrics are qualitatively assessed. The histograms of the DTI metrics were generated for all the individual rodents per site. For inter-site analysis, an average of the individual scans was calculated to create a histogram that represents each site. In order to ensure the analysis can be run at the level of individual animals, the sham and TBI cohort were analyzed separately, which depicted the same harmonization factor. The results demonstrate that these processes qualitatively standardize the file formats, naming conventions, coordinate systems, and DTI metrics of the data. This assists in the ability to share data across the study, as well as disseminate tools that can help other researchers to strengthen the statistical power of their studies and analyze data more cohesively., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Brain atrophy induced by traumatic brain injury (TBI) progresses in parallel with epileptogenesis over time, and thus accurate placement of intracerebral electrodes to monitor seizure initiation and spread at the chronic postinjury phase is challenging. We evaluated in adult male Sprague Dawley rats whether adjusting atlas-based electrode coordinates on the basis of magnetic resonance imaging (MRI) increases electrode placement accuracy and the effect of chronic electrode implantations on TBI-induced brain atrophy. One group of rats (EEG cohort) was implanted with two intracortical (anterior and posterior) and a hippocampal electrode right after TBI to target coordinates calculated using a rat brain atlas. Another group (MRI cohort) was implanted with the same electrodes, but using T2-weighted MRI to adjust the planned atlas-based 3D coordinates of each electrode. Histological analysis revealed that the anterior cortical electrode was in the cortex in 83% (25% in targeted layer V) of the EEG cohort and 76% (31%) of the MRI cohort. The posterior cortical electrode was in the cortex in 40% of the EEG cohort and 60% of the MRI cohort. Without MRI-guided adjustment of electrode tip coordinates, 58% of the posterior cortical electrodes in the MRI cohort will be in the lesion cavity, as revealed by simulated electrode placement on histological images. The hippocampal electrode was accurately placed in 82% of the EEG cohort and 86% of the MRI cohort. Misplacement of intracortical electrodes related to their rostral shift due to TBI-induced cortical and hippocampal atrophy and caudal retraction of the brain, and was more severe ipsilaterally than contralaterally (p < 0.001). Total lesion area in cortical subfields targeted by the electrodes (primary somatosensory cortex, visual cortex) was similar between cohorts (p > 0.05). MRI-guided adjustment of coordinates for electrodes improved the success rate of intracortical electrode tip placement nearly to that at the acute postinjury phase (68% vs. 62%), particularly in the posterior brain, which exhibited the most severe postinjury atrophy. Overall, MRI-guided electrode implantation improved the quality and interpretation of the origin of EEG-recorded signals.

The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force established the TASK3 working groups to create common data elements (CDEs) for various aspects of preclinical epilepsy research studies, which could help improve the standardization of experimental designs. In this article, we discuss CDEs for neuroimaging data that are collected in rodent models of epilepsy, with a focus on adult rats and mice. We provide detailed CDE tables and case report forms (CRFs), and with this companion manuscript, we discuss the methodologies for several imaging modalities and the parameters that can be collected., (© 2022 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)