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Mild therapeutic hypothermia improves neurological outcomes after cardiac arrest by preserving brain function. It is currently under discussion the possibility that hypothermia may also provide a protective effect on cardiac function, in particular, by reducing the infarct size in patients with acute myocardial infarction complicated by cardiac arrest. Despite encouraging experimental and clinical data obtained so far may suggest a potential future indication in this population, routine use of therapeutic hypothermia in acute myocardial infarction patients needs further investigation and it is not currently recommended.

The metabotropic glutamate receptors (mGluRs) are expressed pre- and post synaptically throughout the nervous system where they serve as modulators of synaptic transmission and neuronal excitability. The glutamatergic system is involved in a wide range of physiological processes in the brain, and its dysfunction plays an important role in the etiology and pathophysiology of psychiatric disorders, including schizophrenia. This paper reviews the neurodevelopmental origin and genetic susceptibility of schizophrenia relevant to NMDA receptor neurotransmission, and discusses the relationship between NMDA hypofunction and different domains of symptom in schizophrenia as well as putative treatment modality for the disorder. mGlu receptors have been hypothesizes as attractive therapeutic targets for the development of novel interventions for psychiatric disorders. Group II of mGlu receptors are of particular interest because of their unique distribution and the regulatory roles they have in neurotransmission. The glutamate hypothesis of schizophrenia predicts that agents that restore the balance in glutamatergic neurotransmission will ameliorate the symptomatology associated with this illness. Development of potent, efficacious, systemically active drugs will help to address the antipsychotic potential of these novel therapeutics. This review will discuss recent progress in elucidating the pharmacology and function of group II receptors in the context of current hypotheses on the pathophysiology of schizophrenia and the need for new and better antipsychotics.

Sodium, the most important extracellular fluid electrolyte, is the focus of several homeostatic mechanisms that regulate fluid and electrolyte balance. Hyponatremia is a common electrolyte abnormality caused by an actual sodium deficiency or extracellular compartment fluid excess. Clinical symptoms are related with acuity and speed with which this abnormality is established. The symptoms are mainly neurological and neuromuscular disorders (headache, confusion, stupor, seizures, coma) due to brain cells edema. Hyponatremia due to sodium deficiency is caused by sodium loss from kidney (nephritis, diuretics, mineralocorticoid deficiency) and / or extrarenal (vomiting, diarrhea, burns). Hyponatremia due to water excess seems to be the most common and it is attributable to cirrhosis, nephrotic syndrome, heart failure, infusion 5% glucose solutions and drugs that stimulate ADH secretion. It was recently highlighted the role of inflammation and IL-6 in the non-osmotic ADH release. Hyponatremia is considered also marker of phlogosis. Acute (<48 h) and severe (<125 mEq/ L) hyponatremia is a medical emergency that requires prompt correction. Patients with chronic hyponatremia have a high risk of osmotic demyelination syndrome if rapid correction of the plasmatic sodium occurs. In combination with conventional therapy, a new class of drugs, vasopressin receptors antagonists (AVP-R antagonists) would be able to increase the excretion of electrolyte-free water and the serum sodium concentration.

The erythropoietin is produced by the kidney and other organs. EPO does not only affect erythroid cells, but also other blood cell lines, such as myeloid cells, lymphocytes and megakaryocytes. This hormone can also enhance phagocytes function of the polymorph nuclear cells and reduces the activation of macrophages, thus modulating the inflammatory process. Hematopoietic and endothelial cells probably have the same cellular origin, and the discovery of erythropoietin receptors also on mesangial and myocardial cells and smooth muscle fibro-cells has prompted the study of the pleiotropic actions of this hormone. Through its receptors, spread out over the body, it carries out many actions which range from the erythrogenesis after hypoxic stimuli to the tissue protection of the heart and the brain after ischemia. Erythropoietin also acts in the endothelial proliferation of new vessels involving the tumor genesis, but it opens new frontiers to the employment of rHuEPO in the Regenerative Medicine.

Purpose: Metabolite ratios are the measurements most commonly utilised for clinical applications of brain proton magnetic resonance spectroscopy ((1)H-MRS) [1]. We evaluated the agreement between the metabolite ratios calculated with semiautomatic and automatic software., Materials and Methods: Two single-voxel spectra (3.375 ml) localised in the frontal grey matter (GM) and peritrigonal white matter (WM) were obtained in 20 healthy subjects by using a point-resolved proton spectroscopy sequence (PRESS, TE=144 ms). The spectra were processed using the semiautomatic software J-Magnetic Resonance User Interface (JMRUI) and the automatic software SpectroView. Agreement of the N-acetyl-aspartate (NAA)/creatine (Cr), NAA/choline (Cho) and Cho/Cr ratios calculated with the two methods was assessed by estimating the 95% limits of agreement (LAs) of the differences of the values obtained with the two software packages., Results: Mean values and standard deviations of NAA/Cr, Cho/Cr and NAA/Cho (semiautomatic//automatic software) were 1.99+/-0.53//1.73+/-0.36, 1.13+/-0.40//1.04+/-0.33, 1.85+/-0.62//1.89+/-0.69 for the GM and 2.24+/-0.41//2.37+/-0.27, 0.96+/-0.17//1.13+/-0.15, 2.37+/-0.43//2.11+/-0.23 for the WM. The 95% LAs were wider for GM spectra and ranged between -0.51, 0.17 for Cho/Cr in the WM and -1.54, 1.47 for NAA/Cho in the GM., Conclusions: The difference between brain metabolite ratios calculated with the two software packages is not negligible and reflects spectral quality.

Laughter is a very common behaviour in everyday life, nevertheless scientific literature is lacking in studies which examine closely its nature. The study aims are: to summarise the present knowledge about laughter and its relation with depression and to make hypotheses on its possible therapeutic function. In the first part of the review the main data existing about encephalic structures involved in laughter genesis, which show participation of cortical and subcortical regions, are reported and the effects of laughter on the organism physiologic equilibrium, particularly on the neuroendocrine and immune systems, are described. In the second part, scientific evidence about the influence of depression on the ability to laugh are referred, which suggests that reduction of laughter frequency is a symptom of the disease and that its increase may be used as a marker of clinical improvement. Finally, the main assumptions supporting the hypothesis of the therapeutic action of laughter on depression are examined: first of all, it has been demonstrated that laughter is able to improve mood directly and to moderate negative consequences of stressful events on psychological well-being; in addition, it is possible that the stimulation of particular cerebral regions, involved in depression pathogenesis, and the normalisation of the hypothalamic pituitary adrenocortical system dysfunctions, both mediated by laughter, can counteract efficiently depressive symptoms; finally, the favourable effects of laughter on social relationships and physical health may have a role in influencing the ability of depressed patients to face the disease.

In 1929 Burr and Burr discovered the essential fatty acids omega-6 and omega-3. Since then, researchers have shown a growing interest in unsaturated essential fatty acids as they form the framework for the organism's cell membranes, particularly the neurones in the brain, are involved in the energy-transformation process, regulate the information flows between cells. Polyunsaturated fatty acids are also precursors of ''hormonal'' molecules, often with opposing effects, prostaglandins, prostacyclins, thromboxanes, leukotrienes, lipossines, resolvines, protectines that regulate immunity, platelet aggregation, inflammation, etc. They showed that raised levels of polyunsaturated fatty acids omega-3 in tissue correlate with a reduced incidence of degenerative cardiovascular disease, some mental illnesses such as depression, and neuro-degenerative diseases such as Alzheimer's. The balance between omega-3 and omega-6 acids allows the cell membranes to develop with exactly the right flexibility and fluidity, to carry messages between neurones, that is a determining factor in physical and mental well-being and has a profound influence on all the body's inflammatory responses. The results of a number of scientific studies suggest that omega-3 acids contribute to measuring and restricting inflammatory symptoms, whereas omega-6 acids (and saturated fats) give free range to inflammatory responses and amplify allergic reactions. Today in the Western countries, the ratio of omega-3 acids to omega-6 in the diet is weighted 1:10 in favour of omega-6 to up to 1:25 in some areas, while for proper functioning a 4:1 ratio of omega-6 acids to omega-3 acids is generally considered the optimum. In addition, the type of diet followed in the Western countries is very rich in saturated fats like butter and animal fats, but because of an excessive supply of these less noble fats, the cell membranes lose flexibility and this can affect the way they work. An appropriate supplement can be an efficient, effective and often necessary way to meet the body's needs, enhance its daily functions and promote health and longevity.

Alzheimer's Disease (AD) is the most common neurodegenerative disorder in western societies affecting up to 15 million individuals worldwide.It leads to death after a progressive memory deficit and cognitive impairment accompanied by the appearance of two pathological hallmarks in specific brain areas: neurofibrillary tangles and amyloid plaques. Cholesterol homeostasis may play a key role in AD pathogenesis and this is supported by the demonstration that cholesterol-rich membrane domain, so-called Rafts,are disorganized in affected brains. Retrospective clinical studies indicate that individuals chronically treated with cholesterol synthesis inhibitors,statins, are at lower risk of developing AD but current literature is conflicting with regard to the neuroprotective effects of statins on cognitive impairment. Before recommending statins for prevention and/or treatment of AD it is important to investigate more the role of cholesterol levels in neurodegenerative disorders.

Aims: The present review is aimed to evaluate the recent contribution of brain imaging techniques to the definition of neuroanatomofunctional models of panic disorder (PD)., Methods: Structural and functional brain imaging studies of PD, conducted from January 1993 to October 2003 and selected through a comprehensive Medline search (key-words: panic disorder, emotions, brain imaging, EEG, Event-Related Potentials, MRI, fMRI, PET, SPECT, TC) were included in the review. The Medline search has been complemented by bibliographic cross-referencing., Results: The majority of the reviewed studies suggests that a dysfunction of a neural circuit encompassing prefrontal and temporo-limbic cortices is present in PD. A right hemisphere preferential involvement in PD has been shown by several studies., Conclusions: Reviewed neuroimaging studies suggest a dysfunction of frontal and temporo-limbic circuitries in PD. However, those studies cannot be considered conclusive because of several methodological limitations. Longitudinal and multi-modal studies involving larger patient samples, possibly integrated with population-based and genetic studies, would provide more insight into pathophysiological mechanisms of PD., Declaration of Interest: Authors declare that none of them had any known real, potential, or apparent conflict of interest and that there was no business or personal interest that might be relevant to the topic of this article.

Purpose: Here we report our experience in a general hospital setting using [(123)I]-FP-CIT SPECT to diagnose patients with suspect Parkinson's disease (PD)., Materials and Methods: Thirty consecutive patients (19M, 11W, mean age: 61+/-13 years) were prospectively studied. Patients underwent MRI (27) at 1.5T or CT (3) when MRI was contraindicated, to rule out focal brain abnormalities. Motor and cognitive function were evaluated by neurologists with UPDRS and Hoehn e Yahr Scale. [(123)I]-FP-CIT striatal uptake, assessed with SPECT, was classified as normal, non-diagnostic, abnormal (unilateral or bilateral). Imaging results (SPECT+MRI) were correlated with the neurological findings., Results: In 5 patients the [(123)I]-FP-CIT brain SPECT was normal, suggesting that their symptoms could be related to a benign disorder such as essential tremor. Two patients had non-diagnostic [(123)I]-FP-CIT brain SPECT, with MRI/CT findings compatible with subcortical cerebrovascular disease. In the remaining 23 patients abnormal striatal [(123)I]-FP-CIT uptake correlated with neurological findings, significantly increasing the probability of Parkinson's disease. In these patients MRI/CT scans were normal, or showed a mild BA, or mild cerebral vascular disease (mild CVD)., Conclusions: Our results suggest that [(123)I]-FP-CIT scan could be used routinely in clinical practice to support the diagnosis of PD and to differentiate between other conditions. Moreover, FP-CIT could significantly impact treatment selection and follow-up of these patients.

Three cases of Kearns-Sayre Syndrome are reported, in which some facial anomalies, including facial asymmetry, high forehead, wide nasal bridge, upturned nose, flat philtrum, low set ears and short neck were present. In two cases, the diagnosis of oxidative phosphorylation deficiency was confirmed by hystoenzymatic and genetic studies. The relationship of these facial anomalies with neural crest maldevelopment is emphasized and a classification of the Kearns-Sayre Syndrome as metabolic neurocristopathy is proposed. The facial anomalies are suggestive of an antenatal expression of the oxidative phosphorylation disease.

Anorexia is an often underrated symptom in the clinical management of patients suffering from chronic diseases. Moreover, the anorexia accompanying chronic diseases (secondary anorexia) is often confused with anorexia nervosa, a typically neuropsychiatric disorder involving completely different pathogenic mechanisms and therapeutic strategies. Secondary anorexia is one of the main factors responsible for the development of malnutrition, which in turn negatively affects patient morbidity and mortality. Different mechanisms have been proposed to explain the pathogenesis of secondary anorexia. However, consistent experimental and clinical evidence seems to point to hypothalamic serotonergic system hyperactivity as a preeminent cause; this hyperactivity appears to be triggered by enhanced brain availability of tryptophan, the aminoacid precursor of serotonin. The hyperactive hypothalamic serotonergic system might also represent the final effector where different regulatory and modulating pathways, including cytokines, converge. The involvement of tryptophan and the hypothalamic serotonergic system is further supported by the effectiveness of a therapeutic strategy, based on the inhibition of tryptophan entry into the brain, in increasing the food intake of anorectic patients. Although these results represent an encouraging approach to the treatment of secondary anorexia, with possible beneficial effects on the nutritional status of patients, they need to be validated in larger trials.

Near infrared spectroscopy (NIRS) is a new technique which allows non invasive bedside monitoring of cerebral oxygenation and hemodynamics by measuring relative changes in cerebral oxy- and deoxyhaemoglobin and cytochrome aa3. We have applied this technique to evaluate the possible effects on cerebral oxygenation and hemodynamics of clinical procedures usually performed on preterm infants:--endotracheal suctioning, and we have demonstrated that the magnitude and the duration of the negative effects of open system are significantly reduced using closed endotracheal suctioning system;--withdrawal and infusion through umbilical vein and artery cause significant changes in cerebral hemodynamics: these effects are significantly reduced after administration of ibuprofen;--treatment of patent ductus arteriosus with ibuprofen does not significantly reduce cerebral perfusion and oxygen availability compared to indomethacin and ibuprofen administration also does not affect cerebral vasoreactivity to arterial carbon dioxide tension;--administration of different types and doses of natural surfactant causes different changes in cerebral hemodynamics and these effects seem to be dose-related. Therefore NIRS is an useful device to investigate cerebral oxygenation state of preterm infants and new possibilities could derive from the introduction of a new NIRS method which allows to measure the tissue oxygenation index.

Near infrared spectroscopy (NIRS) is a non invasive, portable, safe technique for monitoring cerebral oxygenation and haemodynamics. A new frequency-domain tissue oximeter based on a multi-distance measurement protocol is presented. The effects of apneic episodes on cerebral and peripheral arterial oxygen saturation (SatO2) in preterm newborns, as monitored by NIRS and by pulse oximetry, are reported. The study population consist of 5 preterms (26 to 30 weeks of gestational age), in the second week of postnatal age, affected by apnea of prematurity. NIRS and pulse oximetric measurements were made contemporarily for a 40-minutes period for each infant. All monitorized apneic events were associated with bradicardia, and resolved spontaneously or after tactile stimulation. As results: a) there was always cerebral deoxygenation in association with apneic events, b) the mean SatO2 as measured by NIRS was slightly lower than the pulse oximeter readings, c) cerebral SatO2 decreased faster and the absolute value of the cerebral SaO2 decrease was greater than that measured peripherally (mean value of 27 versus 13%), d) increases of cerebral deoxyhemoglobin and total hemoglobin and a decrease of oxyhemoglobin were also observed. These preliminary results show that peripheral oxygen saturation measurements as measured by pulse oximetry could not always reflect brain oxygenation.

Therapeutic interventions for acute ischemic stroke have not yet been established in clinical practice. The recognition of an area of reduced blood flow in which neuronal death may be prevented has focused attention on treatments aiming at minimizing ischemic brain damage, if they are initiated within short time after occlusion. The combination of restoring blood flow and providing neuroprotection may be the most productive approach in human acute ischemic stroke, but this combined therapy requires testing through clinical trials. To gain insight into the molecular mechanisms of cerebral ischemia, this review examines the excito-toxic cascade, synthesis and role of nitric oxide and oxidants, gene regulation and possible neuroprotective therapeutic targets. As neuroprotectants, glutamate-antagonists, calcium-antagonists and free radical scavengers have been investigated. The role of nitric oxide is very complex, as it can be cytotoxic or cytoprotective in relation to sources, time of synthesis, and medium redox state. Animal gene studies suggest that nitric oxide produced by endothelial nitric oxide synthase may be advantageous, while nitric oxide produced by neuronal and inducible nitric oxide synthase disadvantageous. A treatment strategy could involve the use of selective inhibitors of different types of nitric oxide synthase. Cell death after cerebral ischemia occurs through the dual pathway of ischemic necrosis and apoptosis. Novel therapies may be directed at genes mediating either recovery or apoptosis. There are, as yet, no conclusive data concerning the safety and efficacy of neuroprotectants in humans. Differences between animal models and clinical conditions may justify the discrepancy between experimental data and clinical practice.

Cortical activity of the brain can be monitored continuously by simple, cheap and non-invasive methods. Nevertheless routine monitoring in Neuro ICUs seldom includes traditional or processed EEG. Our clinical experience with the Cerebral Function Monitor (CFM) indicates that a reliable guide to treatment of acute cerebral lesion can be obtained in different clinical situations and steps of management., Ischemia: the lower border voltage of the CFM correlates with the minimum level of cortical activity and mirrors different degrees of cortical metabolic depression. Cerebral oligaemia is reflected consistently in a an increase in periods of EEG suppression, particularly in the arterial boundary zones where the CFM electrodes are located. CFM is a reliable warning of impending ischaemia., Therapy: during the administration of hypnotics, development of a burst suppression EEG pattern signifies adequate dosage for maximal reduction of cerebral metabolism (CMRO2), cerebral blood flow (CBF) and intracranial pressure. Values of CFM lower border voltage predict the efficacy of hypnotic agents in ICP reduction therapy after severe head injury. Hyperventilation, mannitol and i.v. anaesthetic agents may be beneficial or detrimental in different conditions of CBF and metabolic demand; concomitant recording of oxygen jugular bulb saturation (SjO2) and CFM identifies different clinical situations of the CBF/CMRO2 ratio (adequate perfusion, relative hyperaemia, compensated and non compensated hypoperfusion, cerebral infarct) and offers a clinical guide to targeted therapy., Seizures: generalized and focal sub-clinical seizures are easily recognizable on the CFM trace; continuous EEG/CFM monitoring is mandatory in status epilepticus to choose and titrate drugs., Research: continuous polygraphic recording of CFM together with ABP, ICP and SjO2 is a good method to appreciate spontaneous pathophysiological dynamics and the relationship between treatment, nursing and cerebral events. Frustrating artifacts and "wandering electrodes" could be eliminated by qualified nursing and improved ICU environment; early control of CBF/CMRO2 derangement and prevention of ischaemic secondary damage could take advantage from validated guidelines based on continuous EEG/CFM monitoring.

Whole brain irradiation (WBR) can produce acute and chronic neurological adverse effects, which are usually divided into acute, early delayed and late delayed reactions according to the time of onset. To assess the impact of WBR on brain functional parameters during the early-delayed phase, we employed the [14C]-2-deoxyglucose (2-DG) and the [14C]-alfa-aminoisobutyric (AIB) acid quantitative autoradiographic techniques to study local cerebral glucose utilization and blood-brain barrier permeability, respectively. Sprague-Dowley albino rats were exposed to conventional fractionation (200 Gy/day 5 days a week) for a total dose of 4000 Gy. Experiments were made 3 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. As a rule, brain areas with the highest basal metabolic rates showed the highest percentage drop in glucose utilization. Changes in blood-brain barrier function, as assessed by an increased transcapillary transport of AIB, were also demonstrated in specific brain regions. This study illustrates how moderate doses of WBR induce well-defined changes in brain metabolism and BBB function, which are possibly involved in the pathogenesis of the early-delayed radiation-induced cerebral dysfunction in humans.

A growing body of evidence indicates for ascorbate a very important role in CNS functioning, rather than just fulfilling the relatively passive roles of general reducing agent and enzymatic cofactor. On-going modulation of synaptic events, locomotor activity, intermodulation with the consciousness state, are new fields of ascorbate activity. Several CNS drugs, according to their kind of activity, induce increase or decrease of extracellular brain ascorbate levels; moreover, they can, like d-amphetamine, activate the ascorbate transport system to CNS. Also regional brain ascorbate metabolism can be selectively activated by drugs. Activation of postsynaptic dopaminergic receptors increases ascorbate oxidation in striatum, but not in hypothalamus. Finally, the active transport of ascorbate to neural tissue and its efficient homeostatic system limit the ascorbate therapeutic potential on CNS.

The influence of diet on human behaviour was first postulated several centuries ago, albeit in terms of a magical interpretation of life. Due to our improved knowledge of the basic science, we are now able to provide experimental proof to support this concept. Some opinions, which were once believed to be true, have now been disproved, whereas others have been reconfirmed in physiological terms. This paper aims to evaluate the state of the art in particular with regard to pediatrics. It is now certain that some amino-acids in the diet can influence brain activity by enhancing or reducing the metabolic rates of different neurotransmitters. A modulating effect on the brain has even been suggested with regard to some vitamins and minerals, but data on this aspect are still under evaluation. On the other hand, no data have yet been reported to support the hypothesis of a specific etiological role played by any nutrient in the development of behavioural disturbances.

Recent evidence for the existence of different types and subtypes of serotoninergic receptors has been reviewed. Presently, 5-TH receptors have been divided into 5-HT1, 5-HT2 and 5-HT-3. 5-HT1 receptors have been subdivided into 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D. The development of specific agonists and antagonists to these different types of receptors suggests the possibility of a selective use of these drugs in the treatment of various disorders.

The effects of some antipileptic drugs on the level of GABA in the mouse brain was studied using standardized chromatographic methods. Diphenylhydantoin and carbamazepine determined a marked increase of the cerebral GABA level, whereas phenobarbital, diazepam a,d clonazepam were without effect. The results seem to indicate that diphenyihydantoin and carbamazepine, by increasing the GABA level, may act through an enchancement of the GABA-ergic transmission.

In this study we have measured malonaldehyde (MDA) as an index of endogenous lipoperoxidation, the latter being a relevant aspect of oxidative stress that occurs in different neuronal systems. Our results clearly demonstrate that in physiological conditions specific neuronal systems exhibit a different rate of MDA formation among which substantia nigra neurons show a particular vulnerability to oxidative stress. Chronic ethanol treatment significantly enhances MDA production, particularly at the level of cholinergic structures (septum) as well as in the dopaminergic system (substantia nigra) and cortex. On the other hand, treatment with glutathione is able to decrease MDA formation, pointing out the possibility of an exogenous modulation of redox balance in brain cells.

Intoxication of NMRI Albino mice with bromobenzene is often followed by the appearance of neurological symptoms. The possibility was investigated that the intoxication results in glutathione (GSH) depletion in central nervous systems as seen in other tissues, and that such a depletion is followed by the development of lipid peroxidation. 18-20 hours after bromobenzene administration (15 mmoles/Kg, p.o.) GSH content of prosencephalic and metencephalic regions was depleted by 39 and 55%, respectively. Lipid peroxidation (measured by the tissue content of malonildialdehyde) was observed only when GSH content reached a threshold value, which was different for prosencephalon as compared to metencephalon (2-1.5 mumoles GSH/g and 1.2-0.7 mumoles GSH/g, respectively). Possible mechanisms underlying the phenomenon are discussed.