| 61. |
- Englund, Elisabet
(författare)
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Neuropathology of white matter lesions in vascular cognitive impairment.
- 2002
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 13 Suppl 2:Suppl 2, s. 11-15
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Tidskriftsartikel (refereegranskat)abstract
- The white matter is an important locus for tissue damage in vascular cognitive impairment and white matter lesions often dominate over gray matter changes. The spectrum of ischemic white matter lesions histopathologically represents focal and diffuse lesions, the most common form being the combination of both, in varying proportions. In the combined pathology, the diffuse lesion represents a gradient zone of damage towards surrounding normal tissue and may hold over 200 times the volume of an identified focal lesion, the lacunar infarct. Pathogenetically, the focal lesion results from the acute reaction to regional ischemia, while the diffuse white matter lesion represents the adjustment to altered perfusional and physiological conditions within the tissue. Copyright 2002 S. Karger AG, Basel
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| 62. |
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| 63. |
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| 64. |
- Friberg, Niklas, et al.
(författare)
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Cause of death and significant disease found at autopsy
- 2019
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Ingår i: Virchows Archiv. - : SPRINGER. - 0945-6317 .- 1432-2307. ; 475:6, s. 781-788
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Tidskriftsartikel (refereegranskat)abstract
- The use of clinical autopsy has been in decline for many years throughout healthcare systems of developed countries despite studies showing substantial discrepancies between autopsy results and pre-mortal clinical diagnoses. We conducted a study to evaluate over time the use and results of clinical autopsies in Sweden. We reviewed the autopsy reports and autopsy referrals of 2410 adult (age > 17) deceased patients referred to two University hospitals in Sweden during two plus two years, a decade apart. There was a decline in the number of autopsies performed over time, however, mainly in one of the two hospitals. The proportion of autopsy referrals from the emergency department increased from 9 to 16%, while the proportion of referrals from regular hospital wards was almost halved. The autopsies revealed a high prevalence of cardiovascular disease, with myocardial infarction and cerebrovascular lesion found in 40% and 19% of all cases, respectively. In a large proportion of cases (> 30%), significant findings of disease were not anticipated before autopsy, as judged from the referral document and additional data obtained in some but not all cases. In accordance with previous research, our study confirms a declining rate of autopsy even at tertiary, academic hospitals and points out factors possibly involved in the decline.
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| 65. |
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| 66. |
- Garza, Raquel, et al.
(författare)
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LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification
- 2023
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Ingår i: Science Advances. - 2375-2548. ; 9:44
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Tidskriftsartikel (refereegranskat)abstract
- The genetic mechanisms underlying the expansion in size and complexity of the human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution are largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters are dynamically active in the developing and the adult human brain. L1s generate hundreds of developmentally regulated and cell type-specific transcripts, many that are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived long noncoding RNA, LINC01876, is a human-specific transcript expressed exclusively during brain development. CRISPR interference silencing of LINC01876 results in reduced size of cerebral organoids and premature differentiation of neural progenitors, implicating L1s in human-specific developmental processes. In summary, our results demonstrate that L1-derived transcripts provide a previously undescribed layer of primate- and human-specific transcriptome complexity that contributes to the functional diversification of the human brain.
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| 67. |
- Garza, Raquel, et al.
(författare)
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Single-cell transcriptomics of human traumatic brain injury reveals activation of endogenous retroviruses in oligodendroglia
- 2023
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Ingår i: Cell Reports. - : Elsevier. - 2211-1247. ; 42:11, s. 113395-
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is a leading cause of chronic brain impairment and results in a robust, but poorly understood, neuroinflammatory response that contributes to the long-term pathology. We used single-nuclei RNA sequencing (snRNA-seq) to study transcriptomic changes in different cell populations in human brain tissue obtained acutely after severe, life-threatening TBI. This revealed a unique transcriptional response in oligodendrocyte precursors and mature oligodendrocytes, including the activation of a robust innate immune response, indicating an important role for oligodendroglia in the initiation of neuroinflammation. The activation of an innate immune response correlated with transcriptional upregulation of endogenous retroviruses in oligodendroglia. This observation was causally linked in vitro using human glial progenitors, implicating these ancient viral sequences in human neuroinflammation. In summary, this work provides insight into the initiating events of the neuroinflammatory response in TBI, which has therapeutic implications.
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| 68. |
- Gorcenco, Sorina, et al.
(författare)
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Clinical and genetic analyses of a Swedish patient series diagnosed with ataxia
- 2024
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Ingår i: Journal of Neurology. - 0340-5354. ; 271:1, s. 526-542
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary ataxia is a heterogeneous group of complex neurological disorders. Next-generation sequencing methods have become a great help in clinical diagnostics, but it may remain challenging to determine if a genetic variant is the cause of the patient’s disease. We compiled a consecutive single-center series of 87 patients from 76 families with progressive ataxia of known or unknown etiology. We investigated them clinically and genetically using whole exome or whole genome sequencing. Test methods were selected depending on family history, clinical phenotype, and availability. Genetic results were interpreted based on the American College of Medical Genetics criteria. For high-suspicion variants of uncertain significance, renewed bioinformatical and clinical evaluation was performed to assess the level of pathogenicity. Thirty (39.5%) of the 76 families had received a genetic diagnosis at the end of our study. We present the predominant etiologies of hereditary ataxia in a Swedish patient series. In two families, we established a clinical diagnosis, although the genetic variant was classified as “of uncertain significance” only, and in an additional three families, results are pending. We found a pathogenic variant in one family, but we suspect that it does not explain the complete clinical picture. We conclude that correctly interpreting genetic variants in complex neurogenetic diseases requires genetics and clinical expertise. The neurologist’s careful phenotyping remains essential to confirm or reject a diagnosis, also by reassessing clinical findings after a candidate genetic variant is suggested. Collaboration between neurology and clinical genetics and combining clinical and research approaches optimizes diagnostic yield.
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| 69. |
- Granholm, Ann-Charlotte E, et al.
(författare)
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Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2 : preliminary findings
- 2024
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Ingår i: Acta Neuropathologica. - 1432-0533. ; 147, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.
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| 70. |
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