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- Ström, Jakob, et al.
(författare)
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Effects of high and low 17β-estradiol doses on cerebral ischemia
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION: Estrogens’ effects on cerebral ischemia have during the last two decades been the subject of intense research efforts. Notwithstanding this, the reasons that some studies indicate that estrogens are damaging while others show estrogen-induced neuroprotection has hitherto not been fully elucidated. Recent evidence indicates that discrepancies in hormone administration paradigms, resulting in highly different serum hormone concentrations, may account for this dichotomy. The current study was designed to test this ypothesis.METHODS: Sixty ovariectomized female rats were randomized into three groups differing in subsequent 17β-estradiol regimen (vehicle, low dose and high dose respectively). Following two weeks of treatment, focal cerebral ischemia was induced via an intraluminal filament middle cerebral artery occlusion (MCAo) method. All animals were subjected to a small functional testing battery, and three days after MCAo they were sacrificed for infarct size assessment.RESULTS AND DISCUSSION: The hormone administration regimens significantly affected animal weights and feeding behavior, but infarct sizes did not differ between groups. Further, random intra-group variations in infarct size were too large to allow negative conclusions to be drawn. The large variation was possibly a consequence of too large occluding filament diameter in combination with that the animals were allowed to wake up during ongoing MCAo. After correcting the large variation, the hypothesis needs to be addressed anew.
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- Hoe-Hansen, Carsten, et al.
(författare)
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Acute local inflammation elicits sprouting of sensory axons in the rat supraspinatus tendon
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Inflammation activates nociceptive nerve endings and can elicit local sprouting of axons. We hypothesized that axon sprouting might be one factor behind the emergence of painful inflammatory conditions in the shoulder. Here we examine the distribution of sensory and sympathetic axons in the rat subacromial space under normal conditions and after local induction of inflammation with carrageenan. Furthermore, we measured the neuropeptide content in the supraspinatus tendon. In normal rats protein gene product 9.5- (POP 9.5-), substance P- (SP-), calcitonin gene related peptide- (CGRP-), neuropeptide Y- (NPY-) and tyrosine hydroxylase- (TH-) like immunoreactive (LI) axon profiles occurred in the subacromial space and around the glenohumeral joint. In the supraspinatus tendon axon profiles were limited to the tendon-muscle junction. After carrageenan injection inflammatory cells invaded the tendon and the subacromial bursa with a maximum at 2-3 weeks. Moreover, the tendon and the bursa showed signs of sprouting of PGP-9.5-, SP- and CGRP-LI axons, but not NPY- and TH-LI axons. The tendon was also invaded by blood vessels. The occurrence of axon profiles had a maximum at 2 weeks after injection and then subsided. Also, these axons were GAP-43-LI indicating collateral sprouting of nociceptive nerve fibres. There was no significant increase in the concentration of the neuropeptides SP and CGRP in the supraspinatus tendon. No inflammatory reaction or sprouting of nerve fibres was seen in saline-injected controls. We conclude that an acute inflammation in the subacromial space of the rat shoulder region can elicit a transient local sprouting of sensory axons in the tendon stroma and associated aberrant blood vessels.
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- Hoe-Hansen, Carsten, et al.
(författare)
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Increased Occurrence of Nerve Fibres and some Neuropeptides in Subacromial Tissue Biopsies from Patients with Impingement Syndrome of the Shoulder
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The pathophysiology of subacromial inflammation is not fully understood. In the present study we evaluate the presence of sensory and sympathetic nerve fibres and some neuropeptides in biopsies from the supraspinatus tendon and the subacromial bursa of patients with chronic subacromial inflammation as well as of control cases.Methods: The occurrence of nerve fibres was subjectively assessed by immunohistochemistry. The concentration of substance P (SP), calcitonin generelated peptide (CGRP) and neuropeptide Y (NPY) was measured by radioimmunoassay (RIA).Results: In tendon biopsies from patients with an intact or partially ruptured tendon protein gene product 9.5-like immunoreactive (LI), SP-LI and CGRP-LI nerve fibres were abnormally abundant. In patients with a total tendon rupture nerve fibre occurrence was normal. All biopsies from the bursa exhibited an abnormally high occurrence of SP- and CGRP-LI nerve fibres. In all biopsies the tendon and the bursa contained more blood vessels than normal. The vessels were surrounded by NPY- and tyrosine hydroxylase-LI nerve fibres in a subjectively normal pattern. RIA analysis revealed that the concentration of all three neuropeptides was abnormally high in tendon biopsies from patients with an intact or partially ruptured tendon. Tendon biopsies from patients with total tendon rupture showed statistically normal levels. Biopsies from the bursa showed abnormally high levels of SP and CGRP but normal levels of NPY in all patients.Conclusion: We conclude, that the supraspinatus tendon and the subacromial bursa exhibit an increased occurrence of nerve fibres and some neuropeptides in patients with chronic subacromial inflammation.Clinical relevance: Patients with chronic subacromial inflammation have a disabling pain problem. The increased local occurrence of sensory andsympathetic axons in the inflamed tissues as well as the elevated tissue concentration of certain neuropeptides may represent important factors behind that problem.
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- Karlén, Jerker, et al.
(författare)
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Impact of prenatal psychosocial exposures on hair cortisol levels and child health : cohort study
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background Early psychosocial exposures are increasingly recognized as crucial for health throughout life. A possible mechanism could be physiologic dysregulation due to stress. Cortisol in hair is a new biomarker, assessing long-term HPA axis activity. The objective was to investigate whether prenatal adverse psychosocial circumstances influence infant cortisol levels in hair and health outcome in children prospectively until age 10.Methods True prospective cohort study in the general community with a questionnaire covering 11 psychosocial items in the family during pregnancy formed a composite scale of prenatal psychosocial vulnerability, and cumulative incidence of diseases through diagnoses until age 10 in n=1876 children. At age 1, cortisol levels in hair were measured using a competitive radioimmunoassay on a subsample of n=209.Results Children with added prenatal psychosocial exposures had higher infant cortisol levels in hair (B=0.40, p<0.0001, adjusted for gender and size for gestational age) in a cumulative manner and were more often (p≤0.05) affected by 12 of the 14 most common childhood diagnoses with a general pattern of rising ORs.Conclusions These findings support the model of physiologic dysregulation as a plausible mechanism in how the duration and number of early detrimental psychosocial exposures determine health outcome. It indicates that the multiplicity of adversities should be targeted in future interventions and could help to identify children who are at high risk of poor health. Furthermore, given the prolonged nature of exposure to a stressful social environment, the novel biomarker of cortisol in hair could be of major importance.
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- Rugarn, Olof, et al.
(författare)
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Estradiol causes dose-dependent increase in galanin-like immunoreactivity in both ventral and dorsal hippocampus
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of the study was to investigate the dose- and duration effects of estradiol treatment on galanin-like immunoreactivity in ventral and dorsal rat hippocampus. Ovariectomized rats were treated three, 20 or 60 days with low or high pharmacological doses of estradiol or with carrier only. Galanin-like immunoreactivity was measured with radioimmunoassay using antiserum GalRat4 raised against rat galanin. ANOVA revealed a significant effect from dose (p<0.001) and from duration (p<0.001) of estrogen treatment, but not from region, i.e. ventral or dorsal hippocampus. With the high pharmacological dose, galanin-like immunoreactivity increased more than 10-fold in comparison with the vehicle-treated in dorsal hippocampus and about 6-fold in ventral hippocampus. The increment is most likely due to an effect in the noradrenergic galanin-expressing neurons originating in locus ceruleus. The functional interpretation of these results is dependent on the yet unknown role of galanin in their hippocampal nerve terminals.
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