| 1. |
|
|
| 2. |
- Bryn, V., et al.
(författare)
-
Cytokine Profile in Autism Spectrum Disorders in Children
- 2017
-
Ingår i: Journal of Molecular Neuroscience. - : Springer Science and Business Media LLC. - 0895-8696 .- 1559-1166. ; 61:1, s. 1-7
-
Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of autism spectrum disorders (ASD) is not completely understood, but there is evidence of associations with altered immune responses. The aim of this study was to determine the serum levels of various cytokines in children with ASD and in healthy controls, in order to determine their role in ASD and its diagnostic subgroups. Sixty-five ASD patients were enrolled from an epidemiological survey in Norway, of which 30 were diagnosed with childhood autism, 16 with Asperger syndrome, 12 with atypical autism, 1 with Rett syndrome, and 6 with another ASD diagnosis. The serum levels of 12 cytokines were measured in all of the patients and in 30 healthy children. The cytokine levels did not differ significantly between the ASD group and the healthy controls. However, the interleukin-8 (IL-8) level was significantly higher (6.82 vs 4.58 pg/ml, p = 0.017) while that of IL-10 was significantly lower (2.24 vs 6.49 pg/ml, p = 0.009) in patients with childhood autism than in controls. Furthermore, the IL-8 level was significantly higher in childhood autism than in Asperger syndrome (6.82 vs 4.05 pg/ml, p = 0.013). Our study shows that the cytokine profile of children diagnosed with ASD, regardless of the subdiagnosis, does not differ from healthy controls. However, differentiation into different diagnostic subgroups reveals significantly different levels of IL-8 and IL-10. This indicates that different mechanisms may underlie the different ASD subdiagnoses. Future research into the pathophysiological mechanisms of ASD should pay more attention to the different subdiagnoses of ASD.
|
|
| 3. |
- Bryn, V., et al.
(författare)
-
Kynurenine Pathway in Autism Spectrum Disorders in Children
- 2018
-
Ingår i: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 76:2, s. 82-88
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. Methods: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46.5%) of these patients were diagnosed with childhood autism, 16 (24.6%) with Asperger syndrome, 12 (18.5%) with atypical autism, 1 (1.5%) with Rett syndrome, and 6 (9.2%) with other ASD. The serum levels of the following markers were measured in the children with ASD and compared to those in 30 healthy children: TRP, KYN, kynurenic acid (KA), 3-hydroxykynurenine, and quinolinic acid. Results: The mean serum level of KA was significantly lower in the ASD group than in the healthy controls (28.97 vs. 34.44 nM, p = 0.040), while the KYN/KA ratio was significantly higher in the ASD group (61.12 vs. 50.39, p = 0.006). The same relative values were found when comparing the childhood autism subgroup with the controls. Also, the mean serum level of TRP was significantly lower in children with a subdiagnosis of childhood autism than in those with Asperger syndrome (67.26 vs. 77.79 mu m, p = 0.020). Conclusion: Our study indicates that there is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD. (C) 2018 S. Karger AG, Basel
|
|
| 4. |
- Feet, B A, et al.
(författare)
-
Cerebral excitatory amino acids and Na+,K+-ATPase activity during resuscitation of severely hypoxic newborn piglets
- 1998
-
Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 87:8, s. 889-895
-
Tidskriftsartikel (refereegranskat)abstract
- We tested the hypothesis that early brain recovery in hypoxic newborn piglets is improved by resuscitating with an O2 supply close to the minimum level required by the newborn piglet brain. Severely hypoxic 2-5-d-old anaesthetized piglets were randomly divided into three resuscitation groups: hypoxaemic (n = 8), 21% O2 (n = 8), and 100% O2 groups (n = 8). The hypoxaemic group was mechanically ventilated with 12-18% O2 adjusted to achieve a cerebral venous O2 saturation of 17-23% (baseline; 45 +/- 1%, mean +/- SEM). During the 2h resuscitation period, extracellular aspartate and glutamate concentrations in the cerebral striatum were higher during hypoxaemic resuscitation (p = 0.044 and p = 0.055, respectively) than during resuscitation with 21% O2 or 100% O2, suggesting an unfavourable accumulation of potent excitotoxins during hypoxaemic resuscitation. The cell membrane Na+,K+-ATPase activity of cerebral cortical tissue after 2 h resuscitation was similar in the three groups (p = 0.30). In conclusion, hypoxaemic resuscitation did not normalize early cerebral metabolic recovery as efficiently as resuscitation with 21% O2 or 100% O2. Resuscitation with 21% O2 was as efficient as resuscitation with 100% O2 in this newborn piglet hypoxia model.
|
|
| 5. |
- Feet, B A, et al.
(författare)
-
Early cerebral metabolic and electrophysiological recovery during controlled hypoxemic resuscitation in piglets
- 1998
-
Ingår i: Journal of Applied Physiology. - 1522-1601. ; 84:4, s. 1208-1216
-
Tidskriftsartikel (refereegranskat)abstract
- We tested the hypothesis that controlled hypoxemic resuscitation improves early cerebral metabolic and electrophysiological recovery in hypoxic newborn piglets. Severely hypoxic anesthetized piglets were randomly divided into three resuscitation groups: hypoxemic, 21% O2, and 100% O2 groups (8 in each group). The hypoxemic group was mechanically ventilated with 12-18% O2 adjusted to achieve a cerebral venous O2 saturation of 17-23% (baseline; 45 +/- 1%). Base excess (BE) reached -22 +/- 1 mM at the end of hypoxia. During a 2-h resuscitation period, no significant differences in time to recovery of electroencephalography (EEG), quality of EEG at recovery, or extracellular hypoxanthine concentrations in the cerebral cortex and striatum were found among the groups. BE and plasma hypoxanthine, however, normalized significantly more slowly during controlled hypoxemic resuscitation than during resuscitation with 21 or 100% O2. We conclude that early brain recovery during controlled hypoxemic resuscitation was as efficient as, but not superior to, recovery during resuscitation with 21 or 100% O2. The systemic metabolic recovery from hypoxia, however, was delayed during controlled hypoxemic resuscitation.
|
|
| 6. |
- Kro, G A B, et al.
(författare)
-
A new tool for the validation of umbilical cord acid-base data.
- 2010
-
Ingår i: BJOG : an international journal of obstetrics and gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 117:12, s. 1544-52
-
Tidskriftsartikel (refereegranskat)abstract
- To identify the distribution of carbon dioxide tension (pCO(2) ) relative to pH in validated umbilical cord acid-base data.
|
|
| 7. |
- Ormstad, H., et al.
(författare)
-
Role of the Immune System in Autism Spectrum Disorders (ASD)
- 2018
-
Ingår i: Cns & Neurological Disorders-Drug Targets. - : Bentham Science Publishers Ltd.. - 1871-5273. ; 17:7, s. 489-495
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The evidence based supports that multifactorial and complex immune interactions play a role in autism spectrum disorders (ASD), but contradictory findings are also reported. Objective: The aim of this selective review was to identify trends in the research literature on this topic, focusing on immunology and other aberrations with respect to the different ASD subtypes. Methods: This selective review is based on original and review articles written in English and identified in literature searches of PubMed. Results: Several studies have found that the risk of ASD is greater among children whose mothers suffered from autoimmune diseases while pregnant. Moreover, individuals with ASD show increased levels of antibodies that are specific for several specific proteins. Studies also show that mothers of children with ASD have antibodies against fetal brain proteins. There are also reports on the associations between increased levels of proinflammatory cytokines and ASD. Finally, infections in mothers during pregnancy are linked to an increased risk of ASD. Conclusion: We propose that the large inconsistencies in findings among studies in the field are due to differences in subdiagnoses among the included children with ASD. Well-phenotyped ASD samples are needed to understand the biological and immunological mechanisms underpinning ASD and its subdiagnoses. Future research should apply new strategies to scrutinize the link between ASD and changes in immune responsivity. Important new research avenues are to investigate the associations (a) between different ASD phenotypes and aberrations in (auto) immune pathways and (b) between reduced natural regulatory autoimmune responses during pregnancy, which are in turn associated with increased oxidative and nitrosative stress in maternal blood and putative detrimental effects in the offspring.
|
|
| 8. |
- Ormstad, H., et al.
(författare)
-
Serum Tryptophan, Tryptophan Catabolites and Brain-derived Neurotrophic Factor in Subgroups of Youngsters with Autism Spectrum Disorders
- 2018
-
Ingår i: Cns & Neurological Disorders-Drug Targets. - : Bentham Science Publishers Ltd.. - 1871-5273. ; 17:8, s. 626-639
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is evidence that changes in neuro-immune responses coupled with dysfunctions in serotonin metabolism underpin the pathophysiology of autism spectrum disorders (ASD). Objective: This study aimed to delineate whether ASD subgroups or characteristics show aberrations in tryptophan and brain-derived neurotrophic factor (BDNF) metabolism. Methods: 65 individuals with ASD (diagnosed according to ICD criteria) and 30 healthy control patients were included. Measured were serum levels of tryptophan, kynurenine (KYN), kynurenic acid (KA), quinolinic acid (QA), BDNF and PRO-BDNF and total blood 5-HT and 5-OH-tryptophan (5-HTP). Results: Elevated BDNF levels and lower tryptophan and KA levels were characteristics of both childhood autism and intellectual disability disorder, whilst elevated tryptophan and lower 5-HT synthesis were hallmarks of Asperger syndrome. A pathological MRI was associated with elevated tryptophan and lowered KA. Abnormal EEG results and dysmorphology were both associated with an elevated BDNF/ PRO-BDNF ratio. Any brain pathology and gastro-intestinal symptoms were accompanied by lowered KA. Conclusions: Increased BDNF production and changes in the metabolism of tryptophan are associated with many ASD characteristics, showing particularly strong associations with childhood autism and Intellectual and Developmental Disabilities. Peripheral BDNF and tryptophan metabolism appear to take part in the pathophysiology of autism spectrum disorders and their phenotypes.
|
|
