Landmarks for the Location of the Subthalamic Nucleus Using Magnetic Resonance Imaging

Deep brain stimulation has become an option for advanced Parkinson's disease treatment since the 1990s, but the first reports are from Benabid's team, a French neurosurgeon, in the 1980s. The subthalamic nucleus (STN), more specifically its dorsolateral portion, is the most commonly stimulated brain area. One of the major aspects for a good surgical result is the accurate location of this target. Therefore, the present article aimed to identify landmarks that facilitate and refine the location of the STN using nuclear magnetic resonance imaging (NMRI) of the skull. In order to achieve this goal, a search for articles was performed using the PubMed and Science Direct online databases, and articles regarding the use of NMRI to target STN were included. The precise location of the dorsolateral portion of the STN is fundamental to achieve the best possible effect on motor symptoms and to minimize side effects. One of the most used location methods is the NMRI, associated or not with tomography or ventriculography. The location strategies can be classified as direct and indirect. Landmarks are among the indirect strategies, and the most important ones (red nucleus, Sukeroku sign, dent internal capsule sign, supramammillary commissure, mammillothalamic tract, and interpeduncular cistern) are described in the present article. The various landmarks can be combined to locate with more accuracy the dorsolateral portion of the STN and the ideal position of the electrodes to achieve the best possible clinical result.

Disorders of Consciousness: Practical Management in an Emergency Room

Lowering of the level of consciousness is a very common presentation at the emergency room, often without any history that helps finding an etiology. This emergency requires quick empirical measures to reduce neuronal mortality, with additional protection against sequelae. According to the Advanced Cardiac Life Support (ACLS) guidelines, there are current emergency neurological support protocols, such as the Emergency Neurological Life Support (ENLS) created by the Neurocritical Care Society. The present paper shows how to approach unconscious patients, highlighting possible etiologies and proposed treatments.

Panic-like defensive behavior but not fear-induced antinociception is differently organized by dorsomedial and posterior hypothalamic nuclei of Rattus norvegicus (Rodentia, Muridae)

The hypothalamus is a forebrain structure critically involved in the organization of defensive responses to aversive stimuli. Gamma-aminobutyric acid (GABA)ergic dysfunction in dorsomedial and posterior hypothalamic nuclei is implicated in the origin of panic-like defensive behavior, as well as in pain modulation. The present study was conducted to test the difference between these two hypothalamic nuclei regarding defensive and antinociceptive mechanisms. Thus, the GABA A antagonist bicuculline (40 ng/0.2 µL) or saline (0.9% NaCl) was microinjected into the dorsomedial or posterior hypothalamus in independent groups. Innate fear-induced responses characterized by defensive attention, defensive immobility and elaborate escape behavior were evoked by hypothalamic blockade of GABA A receptors. Fear-induced defensive behavior organized by the posterior hypothalamus was more intense than that organized by dorsomedial hypothalamic nuclei. Escape behavior elicited by GABA A receptor blockade in both the dorsomedial and posterior hypothalamus was followed by an increase in nociceptive threshold. Interestingly, there was no difference in the intensity or in the duration of fear-induced antinociception shown by each hypothalamic division presently investigated. The present study showed that GABAergic dysfunction in nuclei of both the dorsomedial and posterior hypothalamus elicit panic attack-like defensive responses followed by fear-induced antinociception, although the innate fear-induced behavior originates differently in the posterior hypothalamus in comparison to the activity of medial hypothalamic subdivisions.

Normal Sleep in Children and Adolescents / 대한소아신경학회지

Sleep is not just a rest for brain activity during daytime, but also has a vital function for memory consolidation after learning as well as restoration of both body and brain. While restoration of the body mainly occurs during non-rapid eye movement (NREM) sleep, especially during slow wave sleep, restoration of brain and memory consolidation occurs mainly during REM sleep. Adenosine acts as a sleep-inducing agent, so called somnogen or hypnotoxin which accumulates while awake. Sleep deprivation results in the disruption of every aspect of physical, cognitive, and behavioral function, which can be reversed only by sleep. Many neurotransmitter-secreting nuclei in the brain stem, hypothalamus, and basal forebrain are key structures for wakefulness, NREM, and REM sleep. They have been localized in the basal forebrain (acetylcholine), ventrolateral preoptic area (VLPO, GABA and galanin), tuberomamillary nucleus (TMN, histamine), lateral and posterior hypothalamus (orexin/hypocretin), reticular formation (glutamate), substantia nigra/ventral tegmental area (SN/VTA, dopamine), pedunculopontine nucleus and lateral dorsal tegmentum (PPT-LDT, acetylcholine), locus ceruleus (norepinephrine), and the raphe nuclei (serotonin). All are activated during wakefulness except VLPO which secrets GABA and galanin, which suppress other nuclei for sleep induction. Acetylcholine-secreting PPT-LDT is a major locus for REM sleep, and is inhibited by the raphe nuclei and locus ceruleus which act as REM-off neurons inducing NREM sleep. The suprachiasmatic nucleus is a pacemaker for circadian rhythms, which can be modified by bright light and melatonin. It should be emphasized that the best performance of cognitive function including reactivity, abstract thinking, creativity, memory, executive function, and accurate and efficient work as well as physical well-being is achieved by sufficient and appropriate sleep.

Neuroanatomy of Sleep-Wake Regulation and its Application to Pharmacotherapy / 대한정신약물학회지

A current hypothesis of sleep-wake regulation proposes that the sleep process starts with the activation of sleep-promoting neurons located in the preoptic area of the anterior hypothalamus. This activation leads to the inhibition of wake-promoting neurons located in the posterior hypothalamus, basal forebrain, and mesopontine tegmentum, which, in turn removes inhibition from the sleep-promoting structures(i.e., disinhibition) to initiate the sleep process. Mutual inhibition between these wake- and sleep-promoting neurons results in switching properties that define discrete wakeful and sleep states with sharp transitions between them. Wake-promoting nuclei include the orexinergic lateral hypothalamic/perifornical area, the histaminergic tuberomammillary nucleus, the cholinergic pedunculopontine tegmental nucleus, the noradrenergic locus coeruleus, the 5-hydroxytryptaminergic raphe nuclei, and possibly the dopaminergic ventral tegmental area. The major sleep-promoting nucleus is the GABAergic ventrolateral preoptic nucleus of the hypothalamus. The regulation of sleep is classically viewed as the dual interaction of circadian(SCN-based) and homeostatic processes, and the propensity to be asleep or awake at any given time is a consequence of a sleep debt and its interaction with signals from the SCN circadian clock. To better understand the mechanisms of sleep and wakefulness, the focus of pharmacotherapy is on targeting specific therapies to the particular defect in sleep-wake regulation.

Characterization of Norepinephrine Release in Rat Posterior Hypothalamus Using in vivo Brain Microdialysis

In the present study, we used the microdialysis technique combined with high performance liquid chromatography (HPLC) and electrochemical detection to measure the extracellular levels of norepinephrine (NE) in the posterior hypothalamus in vivo, and to examine the effects of various drugs, affecting central noradrenergic transmission, on the extracellular concentration of NE in the posterior hypothalamus. Microdialysis probes were implanted stereotaxically into the posterior hypothalamus (coordinates: posterior 4.3 mm, lateral 0.5 mm, ventral 8 mm, relative to bregma and the brain surface, respectively) of rats, and dialysate collection began 2 hr after the implantation. The baseline level of monoamines in the dialysates were determined to be: NE 0.17 +/- 0.01, 3,4-dihydroxyphenylacetic acid (DOPAC) 0.94 +/- 0.07, homovanillic acid (HVA) 0.57 +/- 0.05 pmol/sample (n=8). When the posterior hypothalamus was perfused with 90 mM potassium, maximum 555% increase of NE output was observed. Concomitantly, this treatment significantly decreased the output of DOPAC and HVA by 35% and 28%, respectively. Local application of imipramine (50microM) enhanced the level of NE in the posterior hypothalamus (maximum 200%) compared to preperfusion control values. But, DOPAC and HVA outputs remained unchanged. Pargyline, an irreversible monoamine oxidase inhibitor, i.p. administered at a dose of 75 mg/kg, increased NE output (maximum 165%), while decreased DOPAC and HVA outputs (maximum 13 and 12%, respectively). These results indicate that NE in dialysate from the rat posterior hypothalamus were neuronal origin, and that manipulations which profoundly affected the levels of extracellular neurotransmitter had also effects on metabolite levels.

effects of atropine and methylatropine on erythropoietin production and hypothalamic stimulation in rabbits

A atropina bloqeia parcialmente o aumento na produção de EPO em coelhos submetidos a hipóxia. Na tentativa de estudar a possibilidade do envolvimento de mecanismos colinérgicos no controle da eritropoiese, a metilatropina foi administrada a coelhos, que, em seguida, foram submetidos a hipóxia hipobárica ou a estimulação do hipotálamo posterior. A metilatropina não bloqueou o aumento na produção de EPO em resposta à hipóxia, nem o aumento na taxa de reticulócitos na circulação periférica. A antropina, que atravessa a barreira hematoencefálica, bloqueia tanto o aumento na produção de EPO, quanto o aumento no número de reticulócitos na circulação periférica

Brain Benzodiazepine-like Molecules and Stress-anxiety Response / 영남의대학술지

Benzodiazepines(BZDs) are among the widely prescribed drugs in the world. They are potent anxiolytic, antiepileptic, hypnotic, and muscle relaxing agents. There is an emerging model of the role of several neural systems in anxiety and their relation to the mechanism of action of BZDs. It has been postulated that BZD drugs exert their anxiolytic action by regulating GABAergic transmission in limbic areas such as the amygdala, in the posterior hypothalamus, and in the raphe nuclei. The involvement of the amygdala in the behaviors triggered by fear and stress has been suggested by many previous studies. In this review, reports about regulatory effects of endogenous BZD receptor ligands on the perception of anxiety and memory consolidation were summerized. These findings further support the contention that BZD receptor ligands modulate memory consolidation of averse learning tasks by influencing the level of stress and/or anxiety that accompanies a learning experience. The findings suggest that the decrease in the limbic levels of BZD-like molecules seen after the various behavioral procedures represent a general response to stress and/or anxiety, since it occurs in proportion to the level of stress and/or anxiety that accompany these tasks. In addition, these findings further support the hypothesis that the GABAA/BZD receptor complex in limbic structures plays a pivotal role in the stress and anxiety.

Primary role of posterior hypothalamic cholinergic receptors in central regulation of blood pressure and heart rate in rats

The purpose of the present study is to determine the role of muscarinic cholinergic receptors of posterior hypothalamus in the central blood pressure regulation when respiration is controlled. In anesthetized and artificially ventilated rats, vasodepressor response was evoked by injection of L-glutamate (10 nmol) neuroexcitatory amino acid into the posterior hypothalamic area. The injection of carbachol (0.5 ~ 8 nmol) into the same area induced dose-dependent vasodepressor and bradycardic responses. Pretreatment with atropine (4 nmol) completely blocked the vasodepressor response to carbachol (2 nmol). In contrast, in spontaneously breathing rats, the injection of carbachol (8 nmol) into the posterior hypothalamic area induced the vasopressor and tachycardic responses. These results suyggest that the muscarinic cholinergic receptors in the posterior hypothalamic area primarily play an inhibitory role in the central regulation of blood pressure and heart rate.

Effect of mutual stimulation of the anterior and posterior hypothalamic nuclei on renal hemodynamics and sodium concentration in plasma

The effect of mutual stimulation of the anterior and posterior hypothalamic nuclei on renal hemodynamics and sodium concentration in plasma was studied in anaesthetized cats. Unilateral renal vasodilation induced by anterior hypothalamic nucleus stimulation resulted in an ipsilateral increase in renal flow and increase in plasma sodium Concentration. Stimulation of the posterior hypothalamic nucleus in the presence of unilateral renal vasodilated kidney resulted in a sustained marked increase in plasms sodium level. These results are consistent with the view that the anterior hypothalamic nucleus stimulation produces a cardiovascular depressor effect and that the posterior hypothalamic nuclei produce a cardiovascular pressor effect. The proper combinations of the two physiological important variables, arterial pressure, renal vascular resistance. can effect large changes in tubular reabsorption of sodium, probably through intrarenal mechanisms

Haemodynamic effects of hypothalamic stimulation on skin and muscle venous beds.

Twenty three points mainly located in the posterior hypothalamus were stimulated to study its effect on the pressures, flows and calculated segmental resistances of the skin and muscle venous beds of hind limbs in the dog. Stimulation of these points produced a uniform pattern of rise in pressures of the muscle veins consisting consisting of a steep rise during stimulation followed by a rapid decline to basal level on its cessation. Skin veins, on the other hand registered a gradual increase in pressure during stimulation followed by a secondary rise during post stimulatory period. Large veins of both muscle and skin exhibited comparatively smaller pressure increases than small vein. These pressure changes were accompanied by a similar marked rise in systemic arterial pressure. Out of 23 points, 21 points produced similar increases in the calculated resistances of skin and muscle veins. Two points produced greater increase of the skin vein resistance. Total venous resistance of the limb was therefore, raised by all the points stimulated. None of these points elicited any fall in the pressures or calculated resistances of either the muscle or skin venous bed. Muscle venous outflow always registered an increase while the skin venous outflow recorded either a small increase or decrease or at times no change during the hypothalamic stimulation. These findings demonstrate that hypothalamic stimulation can profoundly alter the haemodynamics of the hind limb venous beds and actively mobilize the post capillary venous sections of both skin and muscle venous beds.