| 1. |
|
|
| 2. |
- Moretti, R., et al.
(författare)
-
Melatonin reduces excitotoxic blood-brain barrier breakdown in neonatal rats
- 2015
-
Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522. ; 311, s. 382-397
-
Tidskriftsartikel (refereegranskat)abstract
- The blood-brain barrier (BBB) is a complex structure that protects the central nervous system from peripheral insults. Understanding the molecular basis of BBB function and dysfunction holds significant potential for future strategies to prevent and treat neurological damage. The aim of our study was (1) to investigate BBB alterations following excitotoxicity and (2) to test the protective properties of melatonin.Ibotenate, a glutamate analog, was injected intracerebrally in postnatal day 5 (P5) rat pups to mimic excitotoxic injury. Animals were than randomly divided into two groups, one receiving intraperitoneal (i.p.) melatonin injections (5. mg/kg), and the other phosphate buffer saline (PBS) injections. Pups were sacrificed 2, 4 and 18. h after ibotenate injection. We determined lesion size at 5. days by histology, the location and organization of tight junction (TJ) proteins by immunohistochemical studies, and BBB leakage by dextran extravasation. Expression levels of BBB genes (TJs, efflux transporters and detoxification enzymes) were determined in the cortex and choroid plexus by quantitative PCR.Dextran extravasation was seen 2. h after the insult, suggesting a rapid BBB breakdown that was resolved by 4. h. Extravasation was significantly reduced in melatonin-treated pups. Gene expression and immunohistochemical assays showed dynamic BBB modifications during the first 4. h, partially prevented by melatonin. Lesion-size measurements confirmed white matter neuroprotection by melatonin.Our study is the first to evaluate BBB structure and function at a very early time point following excitotoxicity in neonates. Melatonin neuroprotects by preventing TJ modifications and BBB disruption at this early phase, before its previously demonstrated anti-inflammatory, antioxidant and axonal regrowth-promoting effects. © 2015 IBRO.
|
|
| 3. |
- Asa, S L, et al.
(författare)
-
From pituitary adenoma to pituitary neuroendocrine tumor (PitNET) : an International Pituitary Pathology Club proposal
- 2017
-
Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 24:4, s. C5-C8
-
Tidskriftsartikel (refereegranskat)abstract
- The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.
|
|
| 4. |
- Morrow, A., et al.
(författare)
-
Cerebrospinal Fluid Sphingomyelins in Alzheimer's Disease, Neurodegeneration, and Neuroinflammation
- 2022
-
Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 90:2, s. 667-680
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sphingomyelin (SM) levels have been associated with Alzheimer's disease (AD), but the association direction has been inconsistent and research on cerebrospinal fluid (CSF) SMs has been limited by sample size, breadth of SMs examined, and diversity of biomarkers available. Objective: Here, we seek to build on our understanding of the role of SM metabolites in AD by studying a broad range of CSF SMs and biomarkers of AD, neurodegeneration, and neuroinflammation. Methods: Leveraging two longitudinal AD cohorts with metabolome-wide CSF metabolomics data (n = 502), we analyzed the relationship between the levels of 12 CSF SMs, and AD diagnosis and biomarkers of pathology, neurodegeneration, and neuroinflammation using logistic, linear, and linear mixed effects models. Results: No SMs were significantly associated with AD diagnosis, mild cognitive impairment, or amyloid biomarkers. Phosphorylated tau, neurofilament light, alpha-synuclein, neurogranin, soluble triggering receptor expressed on myeloid cells 2, and chitinase-3-like-protein 1 were each significantly, positively associated with at least 5 of the SMs. Conclusion: The associations between SMs and biomarkers of neurodegeneration and neuroinflammation, but not biomarkers of amyloid or diagnosis of AD, point to SMs as potential biomarkers for neurodegeneration and neuroinflammation that may not be AD-specific.
|
|
| 5. |
- Zhukova, Nataliya, et al.
(författare)
-
WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
- 2014
-
Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
|
|
| 6. |
- Mistry, A. K., et al.
(författare)
-
The DESPEC setup for GSI and FAIR
- 2022
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 1033, s. 166662-
-
Tidskriftsartikel (refereegranskat)abstract
- The DEcay SPECtroscopy (DESPEC) setup for nuclear structure investigations was developed and commissioned at GSI, Germany in preparation for a full campaign of experiments at the FRS and Super-FRS. In this paper, we report on the first employment of the setup in the hybrid configuration with the AIDA implanter coupled to the FATIMA LaBr3(Ce) fast-timing array, and high-purity germanium detectors. Initial results are shown from the first experiments carried out with the setup. An overview of the setup and function is discussed, including technical advancements along the path.
|
|
| 7. |
- Andersson, Claes, et al.
(författare)
-
Psychosocial dysfunction is associated with recidivism in crime in paroled offenders
- 2013
-
Ingår i: Alcoholism. - : John Wiley & Sons. - 0145-6008 .- 1530-0277. ; 37:s2, s. 260A-260A
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this research was to study whether automated telephony could be used in paroled offenders to perform daily assessment of variables associated with recidivismin crime, and whether there are grounds for studying the effects of a brief intervention based on these assessments during 30 days following probation. The design included a randomized controlled trial using automated daily assessments and feedback interventions based on Interactive Voice Response (IVR). Participants included paroled offenders (N = 108) during their first 30 days after leaving prison. All subjects were called daily and answered assessment questions. Based on the content of their daily assessments, the subjects in the intervention group received immediate feedback and a recommendation by IVR, and their probation officers also received a daily report by email. Main outcomemeasures (assessed daily) included Stress (Arnetz and Hasson Stress Questionnaire and a revised version of Daily Assessment of Daily Experience), Mood (SCL-8D measuring depression and anxiety), and Use and Urge to Use Alcohol and Drugs (revised version of the Alcohol Urge Questionnaire). Participants were also asked to rate the severity of their most stressful event that day. The outcome variables were analyzed using linear mixed models, presented as group differences between means, 95%CI. Results indicated that the intervention group showed greater improvement than the control group in stress (9.6, 0.5; 18.7, p = 0.038), depression/anxiety (4.6, 0.2; 9.0, p = 0.042), alcohol use (0.8, 0.1; 1.4, p = 0.031), drug use (1.0, 0.5; 1.6, p = 0.000), and in the severity of themost stressful daily event (1.9, 1.1; 2.7, p = 0.000). There were no differences between the groups in the Stress scale and in craving for alcohol and drugs. Overall, the research suggests that in paroled offenders, automated telephony is an effective technology thatmay be used to follow up and to give interventions, resulting in reduced stress and drug use.
|
|
| 8. |
- Deming, Y., et al.
(författare)
-
Neuropathology-based APOE genetic risk score better quantifies Alzheimer's risk
- 2023
-
Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:8, s. 3406-3416
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionApolipoprotein E (APOE) epsilon 4-carrier status or epsilon 4 allele count are included in analyses to account for the APOE genetic effect on Alzheimer's disease (AD); however, this does not account for protective effects of APOE epsilon 2 or heterogeneous effect of epsilon 2, epsilon 3, and epsilon 4 haplotypes. MethodsWe leveraged results from an autopsy-confirmed AD study to generate a weighted risk score for APOE (APOE-npscore). We regressed cerebrospinal fluid (CSF) amyloid and tau biomarkers on APOE variables from the Wisconsin Registry for Alzheimer's Prevention (WRAP), Wisconsin Alzheimer's Disease Research Center (WADRC), and Alzheimer's Disease Neuroimaging Initiative (ADNI). ResultsThe APOE-npscore explained more variance and provided a better model fit for all three CSF measures than APOE epsilon 4-carrier status and epsilon 4 allele count. These findings were replicated in ADNI and observed in subsets of cognitively unimpaired (CU) participants. DiscussionThe APOE-npscore reflects the genetic effect on neuropathology and provides an improved method to account for APOE in AD-related analyses.
|
|
| 9. |
- Keck, Michaela Kristina, et al.
(författare)
-
Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification
- 2023
-
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 145:1, s. 49-69
-
Tidskriftsartikel (refereegranskat)abstract
- Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
|
|
| 10. |
|
|
