LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 103

Search options

  1. Article: The pathological potential of ependymal cells in mild traumatic brain injury.

    Nelles, Diana G / Hazrati, Lili-Naz

    Frontiers in cellular neuroscience

    2023  Volume 17, Page(s) 1216420

    Abstract: Mild traumatic brain injury (mTBI) is a common neurological condition affecting millions of individuals worldwide. Although the pathology of mTBI is not fully understood, ependymal cells present a promising approach for studying the pathogenesis of mTBI. ...

    Abstract Mild traumatic brain injury (mTBI) is a common neurological condition affecting millions of individuals worldwide. Although the pathology of mTBI is not fully understood, ependymal cells present a promising approach for studying the pathogenesis of mTBI. Previous studies have revealed that DNA damage in the form of γH2AX accumulates in ependymal cells following mTBI, with evidence of widespread cellular senescence in the brain. Ependymal ciliary dysfunction has also been observed, leading to altered cerebrospinal fluid homeostasis. Even though ependymal cells have not been extensively studied in the context of mTBI, these observations reflect the pathological potential of ependymal cells that may underlie the neuropathological and clinical presentations of mTBI. This mini review explores the molecular and structural alterations that have been reported in ependymal cells following mTBI, as well as the potential pathological mechanisms mediated by ependymal cells that may contribute to overall dysfunction of the brain post-mTBI. Specifically, we address the topics of DNA damage-induced cellular senescence, dysregulation of cerebrospinal fluid homeostasis, and the consequences of impaired ependymal cell barriers. Moreover, we highlight potential ependymal cell-based therapies for the treatment of mTBI, with a focus on neurogenesis, ependymal cell repair, and modulation of senescence signaling pathways. Further insight and research in this field will help to establish the role of ependymal cells in the pathogenesis of mTBI and may lead to improved treatments that leverage ependymal cells to target the origins of mTBI pathology.
    Language English
    Publishing date 2023-06-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2023.1216420
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Ependymal cells and neurodegenerative disease: outcomes of compromised ependymal barrier function.

    Nelles, Diana G / Hazrati, Lili-Naz

    Brain communications

    2022  Volume 4, Issue 6, Page(s) fcac288

    Abstract: Within the central nervous system, ependymal cells form critical components of the blood-cerebrospinal fluid barrier and the cerebrospinal fluid-brain barrier. These barriers provide biochemical, immunological and physical protection against the entry of ...

    Abstract Within the central nervous system, ependymal cells form critical components of the blood-cerebrospinal fluid barrier and the cerebrospinal fluid-brain barrier. These barriers provide biochemical, immunological and physical protection against the entry of molecules and foreign substances into the cerebrospinal fluid while also regulating cerebrospinal fluid dynamics, such as the composition, flow and removal of waste from the cerebrospinal fluid. Previous research has demonstrated that several neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis, display irregularities in ependymal cell function, morphology, gene expression and metabolism. Despite playing key roles in maintaining overall brain health, ependymal barriers are largely overlooked and understudied in the context of disease, thus limiting the development of novel diagnostic and treatment options. Therefore, this review explores the anatomical properties, functions and structures that define ependymal cells in the healthy brain, as well as the ways in which ependymal cell dysregulation manifests across several neurodegenerative diseases. Specifically, we will address potential mechanisms, causes and consequences of ependymal cell dysfunction and describe how compromising the integrity of ependymal barriers may initiate, contribute to, or drive widespread neurodegeneration in the brain.
    Language English
    Publishing date 2022-11-04
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2632-1297
    ISSN (online) 2632-1297
    DOI 10.1093/braincomms/fcac288
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Brain pathology and symptoms linked to concussion history: beyond chronic traumatic encephalopathy.

    Taskina, Daria / Zhu, Cherrie / Schwab, Nicole / Hazrati, Lili-Naz

    Brain communications

    2024  Volume 6, Issue 2, Page(s) fcad314

    Abstract: Repeated head trauma acquired through sports injuries has been associated with the development of long-term disabling symptoms that negatively impact the quality of life. In this retrospective case series, 52 male former professional athletes involved in ...

    Abstract Repeated head trauma acquired through sports injuries has been associated with the development of long-term disabling symptoms that negatively impact the quality of life. In this retrospective case series, 52 male former professional athletes involved in contact sports and with a history of multiple concussions were evaluated for chronic clinical symptoms and post-mortem neuropathological diagnoses. The clinical symptoms of 19 cases were examined in greater detail for symptom type, severity and duration. Information on neurological, psychiatric and physical symptoms, substance use profiles and concussion histories was obtained from the athletes' next of kin and assessed in relation to post-mortem neuropathological diagnoses. Cases were categorized into three different neuropathological groups: no major neuropathological findings, the presence of only chronic traumatic encephalopathy (CTE) and the diagnosis(es) of other neurodegenerative diseases. Age at death and the presence of DNA damage in the post-mortem brains were analysed for correlation with the clinical symptoms. In this case series, 14/52 (26.9%) cases (mean age 48.2 ± 11.4) had neuropathological evidence of low-stage/low-burden CTE. A total of 11/52 (21.2%) cases (mean age 38.7 ± 12.7) presented a similar profile and severity of behavioural symptoms to those with CTE, despite the lack of significant post-mortem neuropathological findings. A total of 27/52 (51.9%) cases (mean age 75.5 ± 8.7) presented with complex post-mortem neurodegenerative diagnoses, including Alzheimer's disease and other mixed pathologies, and clinical symptoms associated with language, memory and sensory dysfunction. The presence of DNA damage in the brain was found in all neuropathological groups, predominantly in the ependymal lining of ventricles, and phosphorylated histone H2AX staining was correlated with higher age at death (
    Language English
    Publishing date 2024-02-26
    Publishing country England
    Document type Journal Article
    ISSN 2632-1297
    ISSN (online) 2632-1297
    DOI 10.1093/braincomms/fcad314
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Evidence of sex differences in cellular senescence.

    Ng, Mitchell / Hazrati, Lili-Naz

    Neurobiology of aging

    2022  Volume 120, Page(s) 88–104

    Abstract: Biological sex is a factor in many conditions, including aging, neurodegenerative disease, cancer, and more. For each of these, men and women display distinct differences in disease development and progression. To date, studies on the molecular basis of ... ...

    Abstract Biological sex is a factor in many conditions, including aging, neurodegenerative disease, cancer, and more. For each of these, men and women display distinct differences in disease development and progression. To date, studies on the molecular basis of such differences have largely focused on sex hormones, typically highlighting their neuroprotective benefits. However, new research suggests that cellular senescence may underlie sex differences in both neurological and non-neurological pathologies. Cellular senescence-stable proliferative arrest with a unique pro-inflammatory phenotype-occurs in response to persistent DNA damage signaling, safeguarding against tissue-level consequences of DNA damage (e.g., tumorigenesis). Though critical for maintaining tissue health, senescence has also been implicated in disease. Indeed, senescent cell accumulation occurs in multiple disease contexts, and the elimination of such cells (via senolytic therapies) alleviates associated disease hallmarks. If cell senescence is a driver of pathophysiology, sex differences in cellular senescence may underlie sex-specific disease outcomes. This review summarizes evidence of sex differences in cellular senescence-highlighting findings from both human and animal studies-and briefly discusses the potential relevance of sex chromosome epigenetics and mosaicism. Current studies show that female sex is associated with greater susceptibility to DNA damage and greater likelihood of senescence onset, despite additional evidence that estrogen protects against genotoxic insult and inhibits senescence regulatory proteins. Further studies on sex differences in cellular senescence are needed, both to verify whether findings from animal studies hold true in human contexts and to validate whether senescence manifests differently between men and women following comparable senescence-inducing stimuli.
    MeSH term(s) Animals ; Female ; Humans ; Male ; Sex Characteristics ; Neurodegenerative Diseases ; Senotherapeutics ; Cellular Senescence/genetics ; Estrogens
    Chemical Substances Senotherapeutics ; Estrogens
    Language English
    Publishing date 2022-09-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 604505-4
    ISSN 1558-1497 ; 0197-4580
    ISSN (online) 1558-1497
    ISSN 0197-4580
    DOI 10.1016/j.neurobiolaging.2022.08.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Embracing the Unknown in the Diagnosis of Traumatic Encephalopathy Syndrome.

    Hazrati, Lili-Naz / Schwab, Nicole

    Neurology

    2021  Volume 96, Issue 18, Page(s) 835–836

    MeSH term(s) Alzheimer Disease ; Brain Injuries, Traumatic ; Chronic Traumatic Encephalopathy ; Consensus ; Humans ; National Institute of Neurological Disorders and Stroke (U.S.) ; United States
    Language English
    Publishing date 2021-03-15
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000011847
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Breast cancer type 1 and neurodegeneration: consequences of deficient DNA repair.

    Leung, Emily / Hazrati, Lili-Naz

    Brain communications

    2021  Volume 3, Issue 2, Page(s) fcab117

    Abstract: Numerous cellular processes, including toxic protein aggregation and oxidative stress, have been studied extensively as potential mechanisms underlying neurodegeneration. However, limited therapeutic efficacy targeting these processes has prompted other ... ...

    Abstract Numerous cellular processes, including toxic protein aggregation and oxidative stress, have been studied extensively as potential mechanisms underlying neurodegeneration. However, limited therapeutic efficacy targeting these processes has prompted other mechanisms to be explored. Previous research has emphasized a link between cellular senescence and neurodegeneration, where senescence induced by excess DNA damage and deficient DNA repair results in structural and functional changes that ultimately contribute to brain dysfunction and increased vulnerability for neurodegeneration. Specific DNA repair proteins, such as breast cancer type 1, have been associated with both stress-induced senescence and neurodegenerative diseases, however, specific mechanisms remain unclear. Therefore, this review explores DNA damage-induced senescence in the brain as a driver of neurodegeneration, with particular focus on breast cancer type 1, and its potential contribution to sex-specific differences associated with neurodegenerative disease.
    Language English
    Publishing date 2021-05-27
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2632-1297
    ISSN (online) 2632-1297
    DOI 10.1093/braincomms/fcab117
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article: BRCA1 heterozygosity promotes DNA damage-induced senescence in a sex-specific manner following repeated mild traumatic brain injury.

    Leung, Emily / Taskina, Daria / Schwab, Nicole / Hazrati, Lili-Naz

    Frontiers in neuroscience

    2023  Volume 17, Page(s) 1225226

    Abstract: Emerging evidence suggests cellular senescence, as a consequence of excess DNA damage and deficient repair, to be a driver of brain dysfunction following repeated mild traumatic brain injury (rmTBI). This study aimed to further investigate the role of ... ...

    Abstract Emerging evidence suggests cellular senescence, as a consequence of excess DNA damage and deficient repair, to be a driver of brain dysfunction following repeated mild traumatic brain injury (rmTBI). This study aimed to further investigate the role of deficient DNA repair, specifically BRCA1-related repair, on DNA damage-induced senescence. BRCA1, a repair protein involved in maintaining genomic integrity with multiple roles in the central nervous system, was previously reported to be significantly downregulated in post-mortem brains with a history of rmTBI. Here we examined the effects of impaired BRCA1-related repair on DNA damage-induced senescence and outcomes 1-week post-rmTBI using mice with a heterozygous knockout for BRCA1 in a sex-segregated manner. Altered BRCA1 repair with rmTBI resulted in altered anxiety-related behaviours in males and females using elevated zero maze and contextual fear conditioning. Evaluating molecular markers associated with DNA damage signalling and senescence-related pathways revealed sex-specific differences attributed to BRCA1, where females exhibited elevated DNA damage, impaired DNA damage signalling, and dampened senescence onset compared to males. Overall, the results from this study highlight sex-specific consequences of aberrant DNA repair on outcomes post-injury, and further support a need to develop sex-specific treatments following rmTBI.
    Language English
    Publishing date 2023-08-10
    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.2023.1225226
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Author Response: Association of Position Played and Career Duration and Chronic Traumatic Encephalopathy at Autopsy in Elite Football and Hockey Players.

    Wennberg, Richard / Schwab, Nicole / Hazrati, Lili-Naz

    Neurology

    2021  Volume 97, Issue 6, Page(s) 298–299

    MeSH term(s) Athletes ; Autopsy ; Chronic Traumatic Encephalopathy ; Football ; Hockey ; Humans ; Soccer
    Language English
    Publishing date 2021-08-09
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000012382
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Author Response: Association of Position Played and Career Duration and Chronic Traumatic Encephalopathy at Autopsy in Elite Football and Hockey Players.

    Wennberg, Richard / Schwab, Nicole / Hazrati, Lili-Naz

    Neurology

    2021  Volume 97, Issue 6, Page(s) 299–300

    MeSH term(s) Athletes ; Autopsy ; Chronic Traumatic Encephalopathy ; Football ; Hockey ; Humans ; Soccer
    Language English
    Publishing date 2021-08-09
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000012385
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article: Cellular Senescence in Traumatic Brain Injury: Evidence and Perspectives.

    Schwab, Nicole / Leung, Emily / Hazrati, Lili-Naz

    Frontiers in aging neuroscience

    2021  Volume 13, Page(s) 742632

    Abstract: Mild traumatic brain injury (mTBI) can lead to long-term neurological dysfunction and increase one's risk of neurodegenerative disease. Several repercussions of mTBI have been identified and well-studied, including neuroinflammation, gliosis, ... ...

    Abstract Mild traumatic brain injury (mTBI) can lead to long-term neurological dysfunction and increase one's risk of neurodegenerative disease. Several repercussions of mTBI have been identified and well-studied, including neuroinflammation, gliosis, microgliosis, excitotoxicity, and proteinopathy - however the pathophysiological mechanisms activating these pathways after mTBI remains controversial and unclear. Emerging research suggests DNA damage-induced cellular senescence as a possible driver of mTBI-related sequalae. Cellular senescence is a state of chronic cell-cycle arrest and inflammation associated with physiological aging, mood disorders, dementia, and various neurodegenerative pathologies. This narrative review evaluates the existing studies which identify DNA damage or cellular senescence after TBI (including mild, moderate, and severe TBI) in both experimental animal models and human studies, and outlines how cellular senescence may functionally explain both the molecular and clinical manifestations of TBI. Studies on this subject clearly show accumulation of various forms of DNA damage (including oxidative damage, single-strand breaks, and double-strand breaks) and senescent cells after TBI, and indicate that cellular senescence may be an early event after TBI. Further studies are required to understand the role of sex, cell-type specific mechanisms, and temporal patterns, as senescence may be a pathway of interest to target for therapeutic purposes including prognosis and treatment.
    Language English
    Publishing date 2021-09-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2021.742632
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top