V.M.S. de Bruin

Effects of lithium, alone or associated with pilocarpine, on muscarinic and dopaminergic receptors and on phosphoinositide metabolism in rat hippocampus and striatum.

The mechanism of action of lithium (Li) alone or with pilocarpine (Pilo), focusing on muscarinic and dopaminergic systems and also on phosphoinositide metabolism was studied. Li (3 mEq/kg) administered to rats once (1 d) or daily for 7 days (7 d), 24 h before Pilo (15 mg/kg), exacerbated cholinergic signs, leading to tremors. convulsions and brain lesions. Increases in muscarinic receptors (MR) of 29 and 49% were observed in the hippocampus after atropine (Atro) and Li-Atro-Pilo treatments, respectively, as compared to controls (Atro) and the Li-Pilo group (Li-Atro-Pilo). In the striatum, except for the 37% increase in the Li-Atro (50 mg/kg)-Pilo group as compared to the Li-Pilo one, no other changes were observed in MR. A decrease of 32% on average in D2-like receptors (D2R) was detected in the hippocampus in the group Li-7d. On the contrary, in the striatum an increase (25%) in the Li-7d group was observed and this effect was blocked by Li-Pilo. As far as inositol phosphates (IP) and phosphatidylinositol-4,5-biphosphate (PIP2) metabolism is concerned, Li caused a decrease (28%) and an increase (60%) in IP and PIP2 accumulations, respectively, in hippocampus slices while Pilo only altered IP accumulation (32% decrease). In this area the association of Li-Atro (10 mg/kg)-Pilo also caused a decrease (36%) in PIP2 as compared to the Li-Pilo group. In striatal slices, except for the Li, Atro (10 mg/kg) and Li-Atro (10 mg/kg)-Pilo groups which showed a decrease (33 40%) in IP accumulation, no other alteration was detected. The potentiation of the effect of Pilo by Li does not seem to depend on the PI metabolism, but instead on its involvement with muscarinic and dopaminergic systems.

Cortisol and dehydroepiandosterone sulfate plasma levels and their relationship to aging, cognitive function, and dementia.

We have studied the relationship between dehydroepiandrosterone sulfate (DHEAS), cortisol, and cognitive function in a population of demented patients (n=29), age-matched controls (n=46), and younger subjects (n=11). All were submitted to morning collection of blood for determination of plasma cortisol and DHEAS measured by 125I radioimmunoassay. DHEAS levels and cortisol/DHEAS ratios were significantly different among groups with higher DHEAS levels and lower cortisol/DHEAS ratios in younger people (Bonferroni p<.05). Cortisol levels were associated to the presence of dementia (Odds ratio=.93; 95% CI,.86-1.01). There was no difference between DHEAS levels of demented and age-matched controls; however, demented patients showed a trend for higher cortisol/DHEAS ratios than age-matched controls and the latter showed higher ratio values than younger subjects. DHEAS and cortisol plasma values were significantly correlated in all individuals (p<.01). In this study cortisol was independently associated to the presence of dementia.

Inhibitory action of a calcium channel blocker (nimodipine) on seizures and brain damage induced by pilocarpine and lithium-pilocarpine in rats

The present work studied the effect of a calcium channel blocker (nimodipine) on rat behavioural changes and brain lesions observed after seizures induced by high doses of pilocarpine (400 mg/kg, s.c.; P400), and the association of lithium (3 mEq/kg, i.p., daily during 7 days) plus pilocarpine (a single dose of 15 mg/kg, s.c.) administered 24 h after the last injection of lithium. In the P400 model, nimodipine (5 or 10 mg/kg, i.p.) inhibited convulsions, status epilepticus, and significantly decreased the percentage of death and cerebral changes (Mann-Whitney, P = 0.0057). In the lithium-pilocarpine (Li-Pi) induced seizures, nimodipine even increased convulsive action and did not interfere with brain lesions. The results suggested that a calcium channel mechanism is involved in the P400 induced seizures, and that there is a difference in the physiopathology of epileptic seizures and brain damage induced by either P400 and Li-Pi models.

Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease

Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. This randomized, double-blind, placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD. Thirty consecutive patients with moderate to very severe COPD were initially recruited for the study. None of the participants had a history of disease exacerbation 4 weeks prior to the study, obstructive sleep apnea, mental disorders, current use of oral steroids, methylxanthines or hypnotic-sedative medication, nocturnal oxygen therapy, and shift work. Patients received 3 mg melatonin (N = 12) or placebo (N = 13), orally in a single dose, 1 h before bedtime for 21 consecutive days. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness was measured by the Epworth Sleepiness Scale. Pulmonary function and functional exercise level were assessed by spirometry and the 6-min walk test, respectively. Twenty-five patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved global PSQI scores (P = 0.012), particularly sleep latency (P = 0.008) and sleep duration (P = 0.046). No differences in daytime sleepiness, lung function and functional exercise level were observed. We conclude that melatonin can improve sleep in COPD. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

Lipid Peroxidation and Nitrite plus Nitrate Levels in Brain Tissue from Patients with Alzheimer’s Disease

Background: Although oxidative stress has been implicated in the pathogenesis of neurodegenerative diseases, data found in the literature are still a matter of controversy. Objective: To study lipid peroxidation and nitrite plus nitrate levels in brain specimens (frontal, parietal, temporal, and occipital cortices) from 8 patients with Alzheimer’s disease (AD) in comparison to 6 young and 7 age-matched controls. Methods: Lipid peroxidation was estimated by the thiobarbiturate test for malonaldehyde and nitrate/nitrite using the Griess method. Results: Our results show a clear malonaldehyde increase tendency in all brain areas from AD cases in relation to older individuals and younger controls. In temporal cortex there was no difference between AD cases and age-matched controls. We suggest that this may be due to incipient temporal cortex damage in control individuals and that this area could be more susceptible to age-related changes. We showed that nitrite plus nitrate levels significantly decrease in brain areas of AD cases in relation to young controls. Except for the frontal cortex, there was a trend for a decreased concentration of nitrite/nitrate in the aged group in all brain areas studied as compared with young controls. Conclusion: Our results support a major role for lipid peroxidation alterations in cerebral cortex of AD patients and showed not only a decrease in nitrite/nitrate levels in frontal cortex of AD cases in relation to young and old individuals, but also a reduction in these nitric oxide metabolites in the other cortical areas as related to young controls.

Obstructive sleep apnea and biomarkers of inflammation in ischemic stroke

Medeiros CAM, de Bruin VMS, Andrade GM, Coutinho WM, de Castro‐Silva C, de Bruin PFC. Obstructive sleep apnea and biomarkers of inflammation in ischemic stroke.
Acta Neurol Scand: 2012: 126: 17–22.
© 2011 John Wiley & Sons A/S.

Clinical outcome after acute ischaemic stroke: the influence of restless legs syndrome

Background and purpose:  The objective was to evaluate the presence of Restless Legs Syndrome (RLS) in acute stroke, its association with sleep disturbances and clinical outcome during long‐term follow‐up.

Behavioral and Neurochemical Alterations After Lithium–Pilocarpine Administration in Young and Adult Rats: A Comparative Study

Pilocarpine and lithium-pilocarpine can induce seizures and brain damage in adult rats. However, manifestation of cerebral lesions seems to be an age-related phenomenon suggesting that maturational states of neurocircuitry may be involved. We have studied behavior changes, cerebral histopathology, and muscarinic and dopaminergic receptors density in rodents subjected to lithium-pilocarpine treatment. Wistar rats, at two different ages (21 days and 2 months), were treated with pilocarpine (15 mg/kg, SC), lithium (3 mEq/kg, IP), atropine (50 mg/kg, IP) and the combination of lithium to pilocarpine. Histopathologic studies showed that younger animals were more resistant to the development of cerebral changes and there was a preferential involvement of the striatum (Wilcoxon p = 0.02) as opposed to more generalized areas in adult animals such as hippocampus and neocortex. Lithium treatment induced an upregulation of muscarinic receptors at both ages, and this effect was reversed in younger animals after pilocarpine administration. Lithium also induced an upregulation of dopaminergic receptors in the striatum at both ages (p < 0.05), and this effect was not reversed after pilocarpine administration. Our data confirm that young animals show less brain damage after lithium-pilocarpine, and main alterations in dopaminergic receptors density occur in young and older animals after treatment with lithium and lithium combined to a low dose of pilocarpine.

Swallowing dysfunction in Wilson's disease: a scintigraphic study.

Abstract  Although dysphagia is a common complaint of patients with Wilson’s disease (WD) and pneumonia is an important cause of death in these patients, swallowing function remains an underinvestigated field in this condition. The aim of this study was to characterize swallowing dynamics in WD patients. Eight WD patients and 15 age‐matched controls underwent scintigraphic evaluation of oral and pharyngeal deglutition. Patients had significantly slower oral transit (P = 0.008) and a greater percentage of oral residue (P = 0.006) when compared to controls. Two of eight patients were free of neurological symptoms at time of examination. Impaired oropharyngeal function was found in patients without dysphagia and without neurological symptoms. Our findings indicate that WD may present with objective swallowing dysfunction, even in the absence of neurological manifestations. Further studies are necessary to investigate the impact of this dysfunction on morbidity and mortality in WD.