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  1. Article ; Online: Delayed treatment with ceftriaxone reverses the enhanced sensitivity of TBI mice to chemically-induced seizures.

    Romariz, Simone A A / Main, Bevan S / Harvey, Alex C / Longo, Beatriz M / Burns, Mark P

    PloS one

    2023  Volume 18, Issue 7, Page(s) e0288363

    Abstract: The pathophysiological changes that occur after traumatic brain injury (TBI) can lead to the development of post-traumatic epilepsy, a life-long complication of brain trauma. The etiology of post-traumatic epilepsy remains unknown, but TBI brains exhibit ...

    Abstract The pathophysiological changes that occur after traumatic brain injury (TBI) can lead to the development of post-traumatic epilepsy, a life-long complication of brain trauma. The etiology of post-traumatic epilepsy remains unknown, but TBI brains exhibit an abnormal excitatory / inhibitory balance. In this study, we examine how brain injury alters susceptibility to chemically-induced seizures in C57Bl/6J mice, and if pharmacological enhancement of glutamate transporters can reduce chronic post-traumatic seizures. We found that controlled cortical impact (CCI) mice display delayed susceptibility to pentylenetetrazol (PTZ)-induced seizures. While CCI mice have no change in seizure susceptibility at 7d post-injury (dpi), at 70dpi they have reduced latency to PTZ-induced seizure onset, higher seizure frequency and longer seizure duration. Quantification of glutamate transporter mRNA showed that levels of Scl1a2 and Scl1a3 mRNA were increased at 7dpi, but significantly decreased at 70dpi. To test if increased levels of glutamate transporters can ameliorate delayed-onset seizure susceptibility in TBI mice, we exposed a new cohort of mice to CCI and administered ceftriaxone (200mg/kg/day) for 14d from 55-70dpi. We found that ceftriaxone significantly increased Scl1a2 and Scl1a3 in CCI mouse brain at 70dpi, and prevented the susceptibility of CCI mice to PTZ-induced seizures. This study demonstrates cortical impact can induce a delayed-onset seizure phenotype in mice. Delayed (55dpi) ceftriaxone treatment enhances glutamate transporter mRNA in the CCI brain, and reduces PTZ-induced seizures in CCI mice.
    MeSH term(s) Humans ; Mice ; Animals ; Epilepsy, Post-Traumatic ; Ceftriaxone/pharmacology ; Ceftriaxone/therapeutic use ; Time-to-Treatment ; Brain Injuries, Traumatic/complications ; Brain Injuries, Traumatic/drug therapy ; Seizures/chemically induced ; Seizures/drug therapy ; Seizures/complications ; Pentylenetetrazole/toxicity ; Mice, Inbred C57BL ; Glutamates ; Disease Models, Animal
    Chemical Substances Ceftriaxone (75J73V1629) ; Pentylenetetrazole (WM5Z385K7T) ; Glutamates
    Language English
    Publishing date 2023-07-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0288363
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: High Concentrations of Cannabidiol Induce Neurotoxicity in Neurosphere Culture System.

    Romariz, Simone A A / Sanabria, Viviam / da Silva, Karina Ribeiro / Quintella, Miguel L / de Melo, Bruna A G / Porcionatto, Marimélia / de Almeida, Danilo Candido / Longo, Beatriz M

    Neurotoxicity research

    2024  Volume 42, Issue 1, Page(s) 14

    Abstract: Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most studied compounds, has been proposed as a non-toxic option. However, the adverse ... ...

    Abstract Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most studied compounds, has been proposed as a non-toxic option. However, the adverse effects of CBD on neurodevelopmental processes have rarely been studied in cell culture systems. To better understand CBD's influence on neurodevelopment, we exposed neural progenitor cells (NPCs) to different concentrations of CBD (1 µM, 5 µM, and 10 µM). We assessed the morphology, migration, differentiation, cell death, and gene expression in 2D and 3D bioprinted models to stimulate physiological conditions more effectively. Our results showed that CBD was more toxic at higher concentrations (5 µM and 10 µM) and affected the viability of NPCs than at lower concentrations (1 µM), in both 2D and 3D models. Moreover, our study revealed that higher concentrations of CBD drastically reduced the size of neurospheres and the number of NPCs within neurospheres, impaired the morphology and mobility of neurons and astrocytes after differentiation, and reduced neurite sprouting. Interestingly, we also found that CBD alters cellular metabolism by influencing the expression of glycolytic and β-oxidative enzymes in the early and late stages of metabolic pathways. Therefore, our study demonstrated that higher concentrations of CBD promote important changes in cellular functions that are crucial during CNS development.
    MeSH term(s) Humans ; Cannabidiol/toxicity ; Neurotoxicity Syndromes ; Neurons ; Astrocytes ; Carbidopa
    Chemical Substances Cannabidiol (19GBJ60SN5) ; Carbidopa (MNX7R8C5VO)
    Language English
    Publishing date 2024-02-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2036826-4
    ISSN 1476-3524 ; 1029-8428
    ISSN (online) 1476-3524
    ISSN 1029-8428
    DOI 10.1007/s12640-024-00692-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5749: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: What we have learned from non-human primates as animal models of epilepsy.

    Sanabria, Viviam / Romariz, Simone A A / Braga, Matheus / Pires, Jaime Moreira / Naffah-Mazzacoratti, Maria da Graça / Mello, Luiz Eugênio / Longo, Beatriz M / Foresti, Maira Licia

    Epilepsy & behavior : E&B

    2024  Volume 154, Page(s) 109706

    Abstract: Non-human primates (NHPs) have played a crucial role in our understanding of epilepsy, given their striking similarities with humans. Through their use, we have gained a deeper understanding of the neurophysiology and pathophysiology of epileptic ... ...

    Abstract Non-human primates (NHPs) have played a crucial role in our understanding of epilepsy, given their striking similarities with humans. Through their use, we have gained a deeper understanding of the neurophysiology and pathophysiology of epileptic seizures, and they have proven invaluable allies in developing anti-seizure therapies. This review explores the history of NHPs as natural models of epilepsy, discusses the findings obtained after exposure to various chemoconvulsant drugs and focal electrical stimulation protocols that helped uncover important mechanisms related to epilepsy, examines diverse treatments to prevent and manage epilepsy, and addresses essential ethical issues in research. In this review, we aim to emphasize the important role of NHPs in epilepsy research and summarize the benefits and challenges associated with their use as models.
    MeSH term(s) Animals ; Epilepsy/physiopathology ; Primates ; Disease Models, Animal ; Humans
    Language English
    Publishing date 2024-03-21
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2010587-3
    ISSN 1525-5069 ; 1525-5050
    ISSN (online) 1525-5069
    ISSN 1525-5050
    DOI 10.1016/j.yebeh.2024.109706
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5289: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Distinct Effects of the Hippocampal Transplantation of Neural and Mesenchymal Stem Cells in a Transgenic Model of Alzheimer's Disease.

    Campos, Henrique C / Ribeiro, Deidiane Elisa / Hashiguchi, Debora / Hukuda, Deborah Y / Gimenes, Christiane / Romariz, Simone A A / Ye, Qing / Tang, Yong / Ulrich, Henning / Longo, Beatriz Monteiro

    Stem cell reviews and reports

    2022  Volume 18, Issue 2, Page(s) 781–791

    Abstract: Alzheimer's disease (AD) is a severe disabling condition with no cure currently available, which accounts for 60-70% of all dementia cases worldwide. Therefore, the investigation of possible therapeutic strategies for AD is necessary. To this end, animal ...

    Abstract Alzheimer's disease (AD) is a severe disabling condition with no cure currently available, which accounts for 60-70% of all dementia cases worldwide. Therefore, the investigation of possible therapeutic strategies for AD is necessary. To this end, animal models corresponding to the main aspects of AD in humans have been widely used. Similar to AD patients, the double transgenic APPswe/PS1dE9 (APP/PS1) mice show cognitive deficits, hyperlocomotion, amyloid-β (Αβ) plaques in the cortex and hippocampus, and exacerbated inflammatory responses. Recent studies have shown that these neuropathological features could be reversed by stem cell transplantation. However, the effects induced by neural (NSC) and mesenchymal (MSC) stem cells has never been compared in an AD animal model. Therefore, the present study aimed to investigate whether transplantation of NSC or MSC into the hippocampus of APP/PS1 mice reverses AD-induced pathological alterations, evaluated by the locomotor activity (open field test), short- and long-term memory (object recognition) tests, Αβ plaques (6-E10), microglia distribution (Iba-1), M1 (iNOS) and M2 (ARG-1) microglial phenotype frequencies. NSC and MSC engraftment reduced the number of Αβ plaques and produced an increase in M2 microglia polarization in the hippocampus of APP/PS1 mice, suggesting an anti-inflammatory effect of stem cell transplantation. NSC also reversed the hyperlocomotor activity and increased the number of microglia in the hippocampus of APP/PS1 mice. No impairment of short or long-term memory was observed in APP/PS1 mice. Overall, this study highlights the potential beneficial effects of transplanting NSC or MSC for AD treatment.
    MeSH term(s) Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Alzheimer Disease/therapy ; Amyloid beta-Peptides/metabolism ; Animals ; Hippocampus/metabolism ; Hippocampus/pathology ; Humans ; Mesenchymal Stem Cells/metabolism ; Mice ; Mice, Transgenic ; Plaque, Amyloid/pathology
    Chemical Substances Amyloid beta-Peptides
    Language English
    Publishing date 2022-01-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2495577-2
    ISSN 2629-3277 ; 1558-6804 ; 1550-8943
    ISSN (online) 2629-3277 ; 1558-6804
    ISSN 1550-8943
    DOI 10.1007/s12015-021-10321-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6198: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Partial protective effects of cannabidiol against PTZ-induced acute seizures in female rats during the proestrus-estrus transition.

    Janisset, Nilma R L L / Romariz, Simone A A / Hashiguchi, Debora / Quintella, Miguel L / Gimenes, Christiane / Yokoyama, Thais / Filev, Renato / Carlini, Elisaldo / Barbosa da Silva, Regina / Faber, Jean / Longo, Beatriz M

    Epilepsy & behavior : E&B

    2022  Volume 129, Page(s) 108615

    Abstract: Approximately 70% of women with epilepsy experience additional challenges in seizure exacerbation due to hormonal changes, particularly during fluctuations of estrogen-progesterone levels in the menstrual cycle, which is known as catamenial epilepsy. In ... ...

    Abstract Approximately 70% of women with epilepsy experience additional challenges in seizure exacerbation due to hormonal changes, particularly during fluctuations of estrogen-progesterone levels in the menstrual cycle, which is known as catamenial epilepsy. In animal models of epilepsy, a sustained increase in seizure frequency has been observed in female rats during the proestrus-estrus transition when estrogen levels are high and progesterone levels are low resembling catamenial epilepsy. Cannabidiol (CBD) has been proposed to have anticonvulsant and anti-inflammatory effects, able to decrease seizure duration and increase seizure threshold in rats with epilepsy. However, most studies have used males to investigate the pharmacological effects of CBD on seizures, and the neuroprotective effects of CBD against seizures exacerbated by hormonal fluctuations in females are still little explored. Given this scenario, the aim of the present study was to investigate whether CBD would protect against acute seizures induced by pentylenetetrazole (PTZ) in female rats during a pro-convulsant hormonal phase. Therefore, CBD (50 mg/kg) or saline was administered during the proestrus-estrus transition phase, 1 h prior to induction of seizures with PTZ (60 mg/kg), and the following parameters were recorded: duration, latency to first seizure, as well as percentage of convulsing animals (incidence), mortality, and severity of seizures. Brains were processed for immunohistochemistry for microglial cells (Iba-1), and blood was collected for the analysis of cytokines (IL-1β, IL-6, IL-10, and TNF-α). Cannabidiol pre-treated rats showed a significant reduction in duration and severity of seizures, and IL-1β levels, although the latency, incidence of seizures, and mortality rate remained unchanged as well the quantification of microglia in the selected areas. Therefore, acute administration of CBD in a single dose prior to seizure induction showed a partial neuroprotective effect against seizure severity and inflammation, suggesting that female rats in the proconvulsant phase of proestrus-estrus have a low seizure threshold and are more resistant to the anticonvulsant effects of CBD. It appears that other doses or administration windows of CBD may be required to achieve a full protective effect against seizures, suggesting that CBD could be used as an adjunctive therapy during fluctuations of estrogen-progesterone levels. In this sense, considering the hormonal fluctuation as a seizure-potentiating factor, our study contributes to understand the anticonvulsant activity of CBD in females in a pro-convulsant hormonal phase, similar to catamenial seizures in humans.
    MeSH term(s) Animals ; Anticonvulsants/adverse effects ; Cannabidiol/adverse effects ; Disease Models, Animal ; Estrus ; Female ; Humans ; Male ; Pentylenetetrazole/pharmacology ; Proestrus ; Rats ; Seizures/chemically induced ; Seizures/drug therapy
    Chemical Substances Anticonvulsants ; Cannabidiol (19GBJ60SN5) ; Pentylenetetrazole (WM5Z385K7T)
    Language English
    Publishing date 2022-02-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2010587-3
    ISSN 1525-5069 ; 1525-5050
    ISSN (online) 1525-5069
    ISSN 1525-5050
    DOI 10.1016/j.yebeh.2022.108615
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5289: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Medial Ganglionic Eminence Cells Freshly Obtained or Expanded as Neurospheres Show Distinct Cellular and Molecular Properties in Reducing Epileptic Seizures.

    Romariz, Simone A A / Paiva, Daisyléa S / Galindo, Layla T / Barnabé, Gabriela F / Guedes, Vivian A / Borlongan, Cesario V / Longo, Beatriz M

    CNS neuroscience & therapeutics

    2016  Volume 23, Issue 2, Page(s) 127–134

    Abstract: Aims: Medial ganglionic eminence (MGE) progenitors give rise to inhibitory interneurons and may serve as an alternative cell source for large-scale cell transplantation for epilepsy after in vitro expansion. We investigated whether modifications in the ... ...

    Abstract Aims: Medial ganglionic eminence (MGE) progenitors give rise to inhibitory interneurons and may serve as an alternative cell source for large-scale cell transplantation for epilepsy after in vitro expansion. We investigated whether modifications in the culture medium of MGE neurospheres affect neuronal differentiation and expression of MGE-specific genes. In vivo, we compared anticonvulsant effects and cell differentiation pattern among neurospheres grown in different culture media and compared them with freshly harvested MGE cells.
    Methods: We used four variations of cell culture: standard, containing growth factors (EGF/FGF-2) (GF); addition of retinoic acid (GF-RA); withdrawal of EGF/FGF-2 (WD); and addition of retinoic acid and withdrawal of EGF/FGF-2 (WD-RA). Based on in vitro results neurosphere-grown (WD-RA or GF conditions) or fresh MGE cells were transplanted into the hippocampus.
    Results: In vitro WD-RA showed increased neuronal population and higher expression of Dlx1, Nkx2.1, and Lhx6 genes in comparison with GF culture condition. After transplantation, fresh MGE cells and neurospheres (GF) showed anticonvulsant effects. However, fresh MGE cells differentiated preferentially into inhibitory neurons, while GF gave rise to glial cells.
    Conclusion: We conclude that freshly isolated and neurosphere-grown MGE cells reduced seizures by different mechanisms (inhibitory interneurons vs. astrocytes). Fresh MGE cells appear more appropriate for cell therapies targeting inhibitory interneurons for conferring anticonvulsant outcomes.
    MeSH term(s) Animals ; Cell Differentiation/drug effects ; Cells, Cultured ; Creatine/metabolism ; Disease Models, Animal ; Embryo, Mammalian ; Epidermal Growth Factor/pharmacology ; Epilepsy/chemically induced ; Epilepsy/metabolism ; Epilepsy/surgery ; Fibroblast Growth Factor 2/pharmacology ; Glial Fibrillary Acidic Protein/metabolism ; LIM-Homeodomain Proteins/metabolism ; Median Eminence/cytology ; Muscarinic Agonists/toxicity ; Neurons/drug effects ; Neurons/transplantation ; Neuropeptide Y/metabolism ; Parvalbumins/metabolism ; Phosphopyruvate Hydratase/metabolism ; Pilocarpine/toxicity ; Rats ; Rats, Sprague-Dawley ; Tretinoin/pharmacology
    Chemical Substances Glial Fibrillary Acidic Protein ; LIM-Homeodomain Proteins ; Muscarinic Agonists ; Neuropeptide Y ; Parvalbumins ; Pilocarpine (01MI4Q9DI3) ; Fibroblast Growth Factor 2 (103107-01-3) ; Tretinoin (5688UTC01R) ; Epidermal Growth Factor (62229-50-9) ; Phosphopyruvate Hydratase (EC 4.2.1.11) ; Creatine (MU72812GK0)
    Language English
    Publishing date 2016-10-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2423467-9
    ISSN 1755-5949 ; 1755-5930
    ISSN (online) 1755-5949
    ISSN 1755-5930
    DOI 10.1111/cns.12650
    Database MEDical Literature Analysis and Retrieval System OnLINE

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