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  1. Article: Visual evoked potentials waveform analysis to measure intracortical damage in a preclinical model of multiple sclerosis.

    Marenna, Silvia / Rossi, Elena / Huang, Su-Chun / Castoldi, Valerio / Comi, Giancarlo / Leocani, Letizia

    Frontiers in cellular neuroscience

    2023  Volume 17, Page(s) 1186110

    Abstract: Introduction: Visual evoked potentials (VEPs) are a non-invasive technique routinely used in clinical and preclinical practice. Discussion about inclusion of VEPs in McDonald criteria, used for Multiple Sclerosis (MS) diagnosis, increased the importance ...

    Abstract Introduction: Visual evoked potentials (VEPs) are a non-invasive technique routinely used in clinical and preclinical practice. Discussion about inclusion of VEPs in McDonald criteria, used for Multiple Sclerosis (MS) diagnosis, increased the importance of VEP in MS preclinical models. While the interpretation of the N1 peak is recognized, less is known about the first and second positive VEP peaks, P1 and P2, and the implicit time of the different segments. Our hypothesis is that P2 latency delay describes intracortical neurophysiological dysfunction from the visual cortex to the other cortical areas.
    Methods: In this work, we analyzed VEP traces that were included in our two recently published papers on Experimental Autoimmune Encephalomyelitis (EAE) mouse model. Compared with these previous publications other VEP peaks, P1 and P2, and the implicit time of components P1-N1, N1-P2 and P1-P2, were analyzed in blind.
    Results: Latencies of P2, P1-P2, P1-N1 and N1-P2 were increased in all EAE mice, including group without N1 latency change delay at early time points. In particular, at 7 dpi the P2 latency delay change was significantly higher compared with N1 latency change delay. Moreover, new analysis of these VEP components under the influence of neurostimulation revealed a decrease in P2 delay in stimulated animals.
    Discussion: P2 latency delay, P1-P2, P1-N1, and N1-P2 latency changes which reflect intracortical dysfunction, were consistently detected across all EAE groups before N1 change. Results underline the importance of analyzing all VEP components for a complete overview of the neurophysiological visual pathway dysfunction and treatment efficacy.
    Language English
    Publishing date 2023-05-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2023.1186110
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Topical Nerve Growth Factor (NGF) restores electrophysiological alterations in the Ins2

    Castoldi, Valerio / Zerbini, Gianpaolo / Maestroni, Silvia / Viganò, Ilaria / Rama, Paolo / Leocani, Letizia

    Experimental eye research

    2023  Volume 237, Page(s) 109693

    Abstract: People suffering from diabetes mellitus commonly have to face diabetic retinopathy (DR), an eye disease characterized by early retinal neurodegeneration and microvascular damage, progressively leading to sight loss. The ... ...

    Abstract People suffering from diabetes mellitus commonly have to face diabetic retinopathy (DR), an eye disease characterized by early retinal neurodegeneration and microvascular damage, progressively leading to sight loss. The Ins2
    MeSH term(s) Animals ; Mice ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Experimental/metabolism ; Diabetic Retinopathy/metabolism ; Disease Models, Animal ; Insulin/metabolism ; Nerve Growth Factor/pharmacology ; Retina/metabolism
    Chemical Substances Ins2 protein, mouse ; Insulin ; Nerve Growth Factor (9061-61-4)
    Language English
    Publishing date 2023-10-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80122-7
    ISSN 1096-0007 ; 0014-4835
    ISSN (online) 1096-0007
    ISSN 0014-4835
    DOI 10.1016/j.exer.2023.109693
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Improving reproducibility of motor evoked potentials in mice.

    Castoldi, Valerio / Rossi, Elena / Marenna, Silvia / Comi, Giancarlo / Leocani, Letizia

    Journal of neuroscience methods

    2021  Volume 367, Page(s) 109444

    Abstract: Background: In preclinical research involving murine models of neurological diseases, Motor Evoked Potentials (MEPs) can detect pathological alterations in nerve conduction throughout the cortico-spinal tract. In mice, MEPs elicited by electrical ... ...

    Abstract Background: In preclinical research involving murine models of neurological diseases, Motor Evoked Potentials (MEPs) can detect pathological alterations in nerve conduction throughout the cortico-spinal tract. In mice, MEPs elicited by electrical stimulation of the motor cortex can be performed with epicranial or subdermal electrodes such as implanted screws or removable needles, which are associated with invasive surgery and variability in placement of the stimulating electrodes, respectively.
    Methods: We compared MEPs induced by epicranial or subcutaneous stimulation with a non-invasive surface cup electrode over five recording sessions, in healthy C57BL/6 mice. Additionally, using surface stimulation, we examined the recordings obtained with intramuscular needles or surface electrodes to understand if MEP reproducibility could be improved.
    Results: Resting motor threshold (RMT), MEP latency and amplitude were comparable among the different stimulation methods. Epicranial, subcutaneous and surface stimulation techniques presented good repeatability over time, with surface stimulation showing a significantly reduced inter-session variability. Compared with intramuscular needles, MEPs recorded with surface electrode showed reduced peak-to-peak amplitude at all timepoints. RMT and MEP latency were comparable with both recording methods. On the other hand, amplitudes recorded with the surface electrode presented a significantly lower inter-session variance, resulting in improved repeatability.
    Conclusion: Overall, there is evidence for highly reproducible results using different stimulating methods, with indication for reduced inter-session variability for surface stimulation. Moreover, MEP recording with surface electrode provided a decrease in amplitude variability over time, indicating improved measurement stability when considering amplitude as functional outcome in longitudinal studies.
    MeSH term(s) Animals ; Electric Stimulation ; Evoked Potentials, Motor/physiology ; Mice ; Mice, Inbred C57BL ; Motor Cortex ; Reproducibility of Results ; Transcranial Magnetic Stimulation/methods
    Language English
    Publishing date 2021-12-16
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 282721-9
    ISSN 1872-678X ; 0165-0270
    ISSN (online) 1872-678X
    ISSN 0165-0270
    DOI 10.1016/j.jneumeth.2021.109444
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Transcranial direct current stimulation as a preventive treatment in multiple sclerosis? Preclinical evidence.

    Marenna, Silvia / Huang, Su-Chun / Rossi, Elena / Castoldi, Valerio / Comi, Giancarlo / Leocani, Letizia

    Experimental neurology

    2022  Volume 357, Page(s) 114201

    Abstract: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, presenting with optic neuritis in about 20-30% of cases. Optic nerve demyelination, associated with delay of visual evoked potentials (VEPs), is also observed ...

    Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, presenting with optic neuritis in about 20-30% of cases. Optic nerve demyelination, associated with delay of visual evoked potentials (VEPs), is also observed prior to motor signs in the preclinical MS model Experimental Autoimmune Encephalomyelitis (EAE). Transcranial direct current stimulation (tDCS), inducing polarity-dependent changes in neuronal excitability, is widely used to promote neuroplasticity in several neurological disorders. However, its potential effects on inflammation and demyelination are largely unknown. We tested the effectiveness of a preventive, 5-day tDCS treatment started 3 days post-immunization, in reducing the severity of VEP delays observed in early EAE. In mice undergoing cathodal tDCS (n = 6/26 eyes) VEPs were significantly less delayed compared with eyes from EAE-Sham (n = 24/32 eyes) and EAE-Anodal (n = 22/32 eyes). Optic nerve immunohistochemistry revealed a significantly lower cell density of microglia/macrophages, and less axonal loss in EAE-Cathodal vs EAE-Sham and EAE-Anodal, while the percent demyelination with Luxol-fast blue staining was comparable among EAE groups. Considering the latter result, immunofluorescence paranodal staining was performed, revealing a significantly higher number of complete paranode domains in EAE-Cathodal, closer to healthy mice, compared with EAE-Sham and EAE-Anodal groups. These results were reflected by the negative correlation between the number of complete paranode domains and VEP latency increase with respect to pre-immunization. Finally, cathodal tDCS was associated with a lower number, closer to healthy, of single paranodes in contrast to EAE-Sham. The effects of cathodal stimulation in preventing VEPs delays and optic nerve myelin damage were already observed in the pre-motor onset EAE stage, and were associated with a lower density of inflammatory cells. These findings suggest that tDCS may exert an anti-inflammatory effect with potential therapeutic application to be further explored in autoimmune demyelinating diseases.
    MeSH term(s) Animals ; Encephalomyelitis, Autoimmune, Experimental/complications ; Encephalomyelitis, Autoimmune, Experimental/prevention & control ; Evoked Potentials, Visual ; Mice ; Multiple Sclerosis/complications ; Multiple Sclerosis/therapy ; Optic Neuritis/therapy ; Transcranial Direct Current Stimulation
    Language English
    Publishing date 2022-08-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 207148-4
    ISSN 1090-2430 ; 0014-4886
    ISSN (online) 1090-2430
    ISSN 0014-4886
    DOI 10.1016/j.expneurol.2022.114201
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Non-invasive visual evoked potentials under sevoflurane versus ketamine-xylazine in rats

    Castoldi, Valerio / d’Isa, Raffaele / Marenna, Silvia / Comi, Giancarlo / Leocani, Letizia

    Heliyon. 2021 Nov., v. 7, no. 11

    2021  

    Abstract: Visual Evoked Potential (VEP) quantifies electrical signals produced in visual cortex in response to visual stimuli. VEP elicited by light flashes is a useful biomarker to evaluate visual function in preclinical models and it can be recorded in awake or ... ...

    Abstract Visual Evoked Potential (VEP) quantifies electrical signals produced in visual cortex in response to visual stimuli. VEP elicited by light flashes is a useful biomarker to evaluate visual function in preclinical models and it can be recorded in awake or anaesthetised state. Different types of anaesthesia influence VEP properties, such as latency, which measures the propagation speed along nerve fibers, and amplitude that quantifies the power of electrical signal. The goal of this work is to compare VEPs elicited in Dark Agouti rats under two types of anaesthesia: volatile sevoflurane or injectable ketamine-xylazine. VEP latency, amplitude, signal-to-noise ratio and recording duration were measured in Dark Agouti rats randomly assigned to two groups, the first subjected to volatile sevoflurane and the second to injectable ketamine-xylazine. Taking advantage of non-invasive flash-VEP recording through epidermal cup electrodes, three time points of VEP recordings were assessed in two weeks intervals. VEP recorded under ketamine-xylazine showed longer latency and higher amplitude compared with sevoflurane, with analogous repeatability over time. However, sevoflurane tended to suppress electrical signals from visual cortex, resulting in a lower signal-to-noise ratio. Moreover, VEP procedure duration lasted longer in rats anaesthetised with sevoflurane than ketamine-xylazine. In Dark Agouti rats, the use of different anaesthesia can influence VEP components in terms of latency and amplitude. Notably, sevoflurane and ketamine-xylazine revealed satisfying repeatability over time, which is critical to perform reliable follow-up studies. Ketamine-xylazine allowed to obtain more clearly discernible VEP components and less background noise, together with a quicker recording procedure and a consequently improved animal safety and welfare.
    Keywords anesthesia ; biomarkers ; evoked potentials ; nerve tissue ; sevoflurane ; signal-to-noise ratio ; visual cortex
    Language English
    Dates of publication 2021-11
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2021.e08360
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: Non-invasive visual evoked potentials under sevoflurane

    Castoldi, Valerio / d'Isa, Raffaele / Marenna, Silvia / Comi, Giancarlo / Leocani, Letizia

    Heliyon

    2021  Volume 7, Issue 11, Page(s) e08360

    Abstract: Background: Visual Evoked Potential (VEP) quantifies electrical signals produced in visual cortex in response to visual stimuli. VEP elicited by light flashes is a useful biomarker to evaluate visual function in preclinical models and it can be recorded ...

    Abstract Background: Visual Evoked Potential (VEP) quantifies electrical signals produced in visual cortex in response to visual stimuli. VEP elicited by light flashes is a useful biomarker to evaluate visual function in preclinical models and it can be recorded in awake or anaesthetised state. Different types of anaesthesia influence VEP properties, such as latency, which measures the propagation speed along nerve fibers, and amplitude that quantifies the power of electrical signal.
    Aim: The goal of this work is to compare VEPs elicited in Dark Agouti rats under two types of anaesthesia: volatile sevoflurane or injectable ketamine-xylazine.
    Methods: VEP latency, amplitude, signal-to-noise ratio and recording duration were measured in Dark Agouti rats randomly assigned to two groups, the first subjected to volatile sevoflurane and the second to injectable ketamine-xylazine. Taking advantage of non-invasive flash-VEP recording through epidermal cup electrodes, three time points of VEP recordings were assessed in two weeks intervals.
    Results: VEP recorded under ketamine-xylazine showed longer latency and higher amplitude compared with sevoflurane, with analogous repeatability over time. However, sevoflurane tended to suppress electrical signals from visual cortex, resulting in a lower signal-to-noise ratio. Moreover, VEP procedure duration lasted longer in rats anaesthetised with sevoflurane than ketamine-xylazine.
    Conclusions: In Dark Agouti rats, the use of different anaesthesia can influence VEP components in terms of latency and amplitude. Notably, sevoflurane and ketamine-xylazine revealed satisfying repeatability over time, which is critical to perform reliable follow-up studies. Ketamine-xylazine allowed to obtain more clearly discernible VEP components and less background noise, together with a quicker recording procedure and a consequently improved animal safety and welfare.
    Language English
    Publishing date 2021-11-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2021.e08360
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Visual Evoked Potentials to Monitor Myelin Cuprizone-Induced Functional Changes.

    Marenna, Silvia / Huang, Su-Chun / Dalla Costa, Gloria / d'Isa, Raffaele / Castoldi, Valerio / Rossi, Elena / Comi, Giancarlo / Leocani, Letizia

    Frontiers in neuroscience

    2022  Volume 16, Page(s) 820155

    Abstract: The visual system is one of the most accessible routes to study the central nervous system under pathological conditions, such as in multiple sclerosis (MS). Non-invasive visual evoked potential (VEP) and optical coherence tomography (OCT) were used to ... ...

    Abstract The visual system is one of the most accessible routes to study the central nervous system under pathological conditions, such as in multiple sclerosis (MS). Non-invasive visual evoked potential (VEP) and optical coherence tomography (OCT) were used to assess visual function and neuroretinal thickness in C57BL/6 taking 0.2% cuprizone for 7 weeks and at 5, 8, 12, and 15 days after returning to a normal diet. VEPs were significantly delayed starting from 4 weeks on cuprizone, with progressive recovery off cuprizone, becoming significant at day 8, complete at day 15. In contrast, OCT and neurofilament staining showed no significant axonal thinning. Optic nerve histology indicated that whilst there was significant myelin loss at 7 weeks on the cuprizone diet compared with healthy mice, at 15 days off cuprizone diet demyelination was significantly less severe. The number of Iba 1
    Language English
    Publishing date 2022-04-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2022.820155
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Dose-dependent effect of myelin oligodendrocyte glycoprotein on visual function and optic nerve damage in experimental autoimmune encephalomyelitis.

    Castoldi, Valerio / Marenna, Silvia / Huang, Su-Chun / d'Isa, Raffaele / Chaabane, Linda / Comi, Giancarlo / Leocani, Letizia

    Journal of neuroscience research

    2022  Volume 100, Issue 3, Page(s) 855–868

    Abstract: Female Dark Agouti rats were immunized with increasing doses of myelin oligodendrocyte glycoprotein (MOG) to develop experimental autoimmune encephalomyelitis (EAE), a preclinical model of multiple sclerosis. Typical EAE motor impairments were assessed ... ...

    Abstract Female Dark Agouti rats were immunized with increasing doses of myelin oligodendrocyte glycoprotein (MOG) to develop experimental autoimmune encephalomyelitis (EAE), a preclinical model of multiple sclerosis. Typical EAE motor impairments were assessed daily and noninvasive visual evoked potentials (VEPs) were recorded at baseline and 5 weeks after immunization, with final histopathology of optic nerves (ONs). Immunized rats exhibited a relapsing-remitting clinical course. Both VEP and histological abnormalities were detected in a MOG dose-dependent gradient. Increasing MOG dosage augmented visual function impairment in EAE, which could be monitored with VEP recording to assess demyelination and axonal loss along ONs.
    MeSH term(s) Animals ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Evoked Potentials, Visual ; Female ; Multiple Sclerosis/pathology ; Myelin-Associated Glycoprotein ; Myelin-Oligodendrocyte Glycoprotein/toxicity ; Optic Nerve/pathology ; Rats
    Chemical Substances Myelin-Associated Glycoprotein ; Myelin-Oligodendrocyte Glycoprotein
    Language English
    Publishing date 2022-01-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 195324-2
    ISSN 1097-4547 ; 0360-4012
    ISSN (online) 1097-4547
    ISSN 0360-4012
    DOI 10.1002/jnr.25007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: MCT1-dependent energetic failure and neuroinflammation underlie optic nerve degeneration in Wolfram syndrome mice.

    Rossi, Greta / Ordazzo, Gabriele / Vanni, Niccolò N / Castoldi, Valerio / Iannielli, Angelo / Di Silvestre, Dario / Bellini, Edoardo / Bernardo, Letizia / Giannelli, Serena G / Luoni, Mirko / Muggeo, Sharon / Leocani, Letizia / Mauri, PierLuigi / Broccoli, Vania

    eLife

    2023  Volume 12

    Abstract: Wolfram syndrome 1 (WS1) is a rare genetic disorder caused by mutations in ... ...

    Abstract Wolfram syndrome 1 (WS1) is a rare genetic disorder caused by mutations in the
    MeSH term(s) Animals ; Mice ; Nerve Degeneration/metabolism ; Neuroinflammatory Diseases ; Optic Atrophy ; Retinal Ganglion Cells/metabolism ; Wolfram Syndrome/genetics ; Wolfram Syndrome/metabolism
    Chemical Substances monocarboxylate transport protein 1
    Language English
    Publishing date 2023-01-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.81779
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  10. Article ; Online: Semi-invasive and non-invasive recording of visual evoked potentials in mice.

    Marenna, Silvia / Castoldi, Valerio / d'Isa, Raffaele / Marco, Cursi / Comi, Giancarlo / Leocani, Letizia

    Documenta ophthalmologica. Advances in ophthalmology

    2019  Volume 138, Issue 3, Page(s) 169–179

    Abstract: Purpose: Visual evoked potentials (VEPs) are used to assess visual function in preclinical models of neurodegenerative diseases. VEP recording with epidural screw electrodes is a common method to study visual function in rodents, despite being an ... ...

    Abstract Purpose: Visual evoked potentials (VEPs) are used to assess visual function in preclinical models of neurodegenerative diseases. VEP recording with epidural screw electrodes is a common method to study visual function in rodents, despite being an invasive procedure that can damage the tissue under the skull. The present study was performed to test a semi-invasive (epicranial) and a non-invasive (epidermal) VEP recording technique, comparing them with the classic epidural acquisition method.
    Methods: Flash VEPs were recorded from C57BL/6 mice on three separate days within 2 weeks. Waveforms, latencies and amplitudes of the components were compared between the three different methods, utilizing coefficient of repeatability, coefficient of variation and intersession standard deviation to evaluate reproducibility.
    Results: While epidural electrodes succeeded in recording two negative peaks (N1 and N2), epicranial and epidermal electrodes recorded a single peak (N1). Statistical indexes showed a comparable reproducibility between the three techniques, with a greater stability of N1 latency recorded through epicranial electrodes. Moreover, N1 amplitudes recorded with the new less-invasive methods were more reproducible compared to the invasive gold-standard technique.
    Conclusions: These results demonstrate the reliability of semi- and non-invasive VEP recordings, which can be useful to evaluate murine models of neurological diseases.
    MeSH term(s) Animals ; Electrodes ; Electroretinography ; Epidermis ; Evoked Potentials, Visual/physiology ; Female ; Mice ; Mice, Inbred C57BL ; Photic Stimulation/methods ; Reproducibility of Results ; Visual Pathways/physiology
    Language English
    Publishing date 2019-03-06
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 212594-8
    ISSN 1573-2622 ; 0012-4486
    ISSN (online) 1573-2622
    ISSN 0012-4486
    DOI 10.1007/s10633-019-09680-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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