A.A. de Rotte

Relationships between α-MSH levels in blood and in cerebrospinal fluid

Using a new cannulation technique of the cisterna magna of the rat, CSF was obtained in which α-MSH levels were determined under various conditions and were compared with a-MSH levels in plasma. Basal levels of 66 ± 9 pg α-MSH/ml were found in the CSF and of 179 ± 13 pg α-MSH/ml in the plasma. A rapid flow of CSF from the lateral ventricles to the cisterna magna could be established as detected by elevated α-MSH levels in cisternal CSF 2 min after injection of a large quantity of α-MSH into the ventricular system. A half-time disappearance of α-MSH from the CSF of 33 min was calculated. The possibility of a contribution of peripheral α-MSH to central melanotropic activity was suggested by the finding of elevated levels of α-MSH in the CSF, following artificially induced high α-MSH concentrations in the blood. Additionally, the movement of α-MSH from the CSF to the blood was demonstrated. Both these movements were shown to be independent of the pituitary gland, since hypophysectomized animals exhibited the same rate of α-MSH transport as intact animals.

Plaque at RISK (PARISK): Prospective Multicenter Study to Improve Diagnosis of High-Risk Carotid Plaques

Background Patients with symptomatic carotid artery stenosis are at high risk for recurrent stroke. To date, the decision to perform carotid endarterectomy in patients with a recent cerebrovascular event is mainly based on degree of stenosis of the ipsilateral carotid artery. However, additional atherosclerotic plaque characteristics might be better predictors of stroke, allowing for more precise selection of patients for carotid endarterectomy. Aims and hypothesis We investigate the hypothesis that the assessment of carotid plaque characteristics with magnetic resonance imaging, multidetector-row computed tomography angiography, ultrasonography, and transcranial Doppler, either alone or in combination, may improve identification of a subgroup of patients with <70% carotid artery stenosis with an increased risk of recurrent stroke. Methods The Plaque At RISK (PARISK) study is a prospective multicenter cohort study of patients with recent (<3 months) neurological symptoms due to ischemia in the territory of the carotid artery and < 70% ipsilateral carotid artery stenosis who are not scheduled for carotid endarterectomy or stenting. At baseline, 300 patients will undergo magnetic resonance imaging, multidetector-row computed tomography angiography, and ultrasonography examination of the carotid arteries. In addition, magnetic resonance imaging of the brain, ambulatory transcranial Doppler recording of the middle cerebral artery and blood withdrawal will be performed. After two-years, imaging will be repeated in 150 patients. All patients undergo a follow-up brain magnetic resonance imaging, and there will be regular clinical follow-up until the end of the study. Study outcomes The combined primary end-point contains ipsilateral recurrent ischemic stroke or transient ischemic attack or new ipsilateral ischemic brain lesions on follow-up brain magnetic resonance imaging.

Involvement of ACTH and MSH in active and passive avoidance behavior.

Intracerebroventricular injection of antiserum to alpha--MSH induces a weak reduction of passive avoidance latencies after administration prior to retention testing. Administration of antiserum to ACTH 1--24 induces a more marked effect in this respect, whereas injection of a combination of these antisera results in the strongest reduction of passive avoidance retention. No effect of this treatment is observed when these antisera are injected immediately after the learning trial. In active avoidance behavior a facilitation of extinction of the response is observed after intracerebroventricular administration of the antisera prior to each extinction session. This effect is comparable with the one observed in passive avoidance behavior. From these data it is suggested that ACTH and alpha-MSH play an important role in processes related to the retrieval of information stored in the brain.

Plasma and cerebrospinal fluid α-MSH levels in the rat after hypophysectomy and stimulation of pituitary α-MSH secretion

Immunoreactive α-MSH was measured in cerebrospinal fluid (CSF) and plasma of rats. While treatment with haloperidol increased α-MSH levels in the plasma concentration of α-MSH in the CSF showed little change. Hypophysectomy also had little effect on the concentration of α-MSH in the CSF despite the fall in plasma α-MSH levels. This lack of correlation between α-MSH levels in the CSF and plasma suggests that the systemic circulation does not deliver α-MSH to the CSF. The apparently normal levels of α-MSH in the hypothalamus after hypophysectomy suggests that this tissue is able to synthesize α-MSH and it is possible that the hypothalamus is a source of the α-MSH in the CSF.

Intraplaque Hemorrhage and the Plaque Surface in Carotid Atherosclerosis: The Plaque At RISK Study (PARISK).

BACKGROUND AND PURPOSE: An important characteristic of vulnerable plaque, intraplaque hemorrhage, may predict plaque rupture. Plaque rupture can be visible on noninvasive imaging as a disruption of the plaque surface. We investigated the association between intraplaque hemorrhage and disruption of the plaque surface. MATERIALS AND METHODS: We selected the first 100 patients of the Plaque At RISK study, an ongoing prospective noninvasive plaque imaging study in patients with mild-to-moderate atherosclerotic lesions in the carotid artery. In carotid artery plaques, disruption of the plaque surface (defined as ulcerated plaques and/or fissured fibrous cap) and intraplaque hemorrhage were assessed by using MDCTA and 3T MR imaging, respectively. We used a χ2 test and multivariable logistic regression to assess the association between intraplaque hemorrhage and disrupted plaque surface. RESULTS: One hundred forty-nine carotid arteries in 78 patients could be used for the current analyses. Intraplaque hemorrhage and plaque ulcerations were more prevalent in symptomatic compared with contralateral vessels (hemorrhage, 38% versus 11%; P < .001; and ulcerations, 27% versus 7%; P = .001). Fissured fibrous cap was more prevalent in symptomatic compared with contralateral vessels (13% versus 4%; P = .06). After adjustment for age, sex, diabetes mellitus, and degree of stenosis, intraplaque hemorrhage was associated with disrupted plaque surface (OR, 3.13; 95% CI, 1.25–7.84) in all vessels. CONCLUSIONS: Intraplaque hemorrhage is associated with disruption of the plaque surface in patients with a carotid artery stenosis of <70%. Serial studies are needed to investigate whether intraplaque hemorrhage indeed increases the risk of plaque rupture and subsequent ischemic stroke during follow-up.

α-MSH levels in cerebrospinal fluid and blood of rats during behavioral manipulations

Abstract It was shown previously that α-MSH levels in peripheral blood of rats subjected to passive avoidance training did not correlate with the behavioral performance of the animals. We have investigated whether α-MSH levels in cerebrospinal fluid (CSF) change during passive avoidance behavior. It appeared that throughout adaptation, acquisition and retention of this avoidance behavior, α-MSH levels in the CSF did not change significantly. In an additional experiment in which the effects of an electric footshock versus a psychological stimulus were tested, α-MSH levels in CSF also remained unchanged. Since CSF α-MSH levels appear to be relatively stable under these behavioral conditions, it seems unlikely that the CSF functions as a direct and specific route for the afferent transport of the behaviorally active neuropeptide α-MSH to its sites of action in the brain. However, the psychological stimulus, which consisted of the fear of receiving an unavoidable electric footshock, did induce a significant enhancement of α-MSH levels in peripheral blood, suggesting that psychological stress may be involved in the release of α-MSH into the peripheral circulation. These results support the idea of a differentiated system of secretion of α-MSH into CSF and peripheral blood.

Plaque Components in Symptomatic Moderately Stenosed Carotid Arteries Related to Cerebral Infarcts: The Plaque at RISK Study

Large randomized controlled trials have demonstrated that patients with a symptomatic 70% to 99% stenosis of the carotid artery benefit most from carotid endarterectomy. In line with these results, decision making for patients with a symptomatic carotid artery stenosis is currently based on the degree of stenosis. Nevertheless, in the past decades, research has demonstrated that atherosclerotic plaque components may also play a role in risk assessment of these patients. Previous MRI studies suggest a correlation between specific carotid plaque components and the presence of cerebral infarcts on MRI, as well as clinical events during follow-up. The aim of the present cross-sectional study is to evaluate the association between intraplaque hemorrhage (IPH) and a thin/ ruptured fibrous cap (TRFC) and the presence of infarcts on MRI in patients with a symptomatic 30% to 69% carotid artery stenosis. Vulnerable plaque components, such as IPH, remain detectable in the plaque even after 18 months. Therefore, we hypothesize that both old and recent infarcts might be related to vulnerable carotid plaque components as assessed on MRI. Because not all subcortical infarcts are considered to be a result from large-vessel disease, in contrast to cortical infarcts, we evaluate both cortical and total amount of infarcts.