Soft biomaterials as a substitute for the Nucleus Pulposus

One of the largest health problems faced worldwide, when evaluated by direct (clinical) as well indirect cost (absenteeism), is the degeneration of the intervertebral disc (IVD) that leads to back pain and, potentially disability and individual´s quality of life decreasing. The intervertebral disc is a mechanical and biological complex structure, formed by a tough outer layer of fibrocartilage called Annulus Fibrosus (AF),which surrounds a soft, elastic and gelatinous core called Nucleus Pulposus (NP). These two structures are completed by two upper and lower encasing layer called Vertebral Endplates (VEP). The degeneration of the IVD is marked by the dehydration of the Nucleus Pulposus, reducing the hydrostatic pressure inside the nucleus, resulting in a loss of capability to support compressive forces, during the active period, and to regain height during the resting period. This situation will compromise the role of shock absorber by the NP and transfers these forces to the AF. This transfer will result in cracks on the AF, deteriorating the IVD, allowing the ingrowth of vessels and nerves. This project was based on the developing a protocol to test suitable NP replacements, in hope to future assessment of discrete mechanical values and characteristics for an NP replacement. For this, Nucleus pulposus samples from goat, encapsulated Hydromed gel denominated “Raviolis” and Chitosan gels, produced via wet route using an ammonium environment, were confined compressed. Chitosan was rheologically tested and swelling capability of all the three type of materials was assessed. Results showed that the Nucleus Pulposus and “Raviolis” have similar mechanical behavior, being able to swell and “build up” hydrostatic pressure after a compression stage, while the Chitosan gel did not showed that ability. Therefore, “Raviolis” are a more suitable candidate to replace the NP than Chitosan gels. It was also observed that confined compression is the key test to perform on any possible candidate to replace the NP.

Volumetric alterations in the nucleus accumbens and caudate nucleus in bulimia nervosa: a structural magnetic resonance imaging study

Bulimia nervosa (BN) is an eating disorder characterized by recurrent episodes of binge eating and inappropriate compensatory behaviors (such as purging, fasting, or excessive exercise) to prevent weight gain. BN has been associated with deficits in inhibitory control processes. The basal ganglia specifically, the nucleus accumbens (NAc) and the caudate nucleus (CN) are part of the frontostriatal circuits involved in inhibitory control. The main goal of this study was to investigate the presence of morphological alterations in the NAc and the CN in a sample of patients diagnosed with BN.

Antidepressant induced excessive yawning and indifference

Introduction Antidepressant induced excessive yawning has been described as a possible side effect of pharmacotherapy. A syndrome of indifference has also been described as another possible side effect. The frequency of those phenomena and their physiopathology are unknown. They are both considered benign and reversible after antidepressant discontinuation but severe cases with complications as temporomandibular lesions, have been described. Methods We report two unprecedented cases in which excessive yawning and indifference occurred simultaneously as side effects of antidepressant therapy, discussing possible physiopathological mechanisms for this co-occurrence. Case 1: A male patient presented excessive yawning (approximately 80/day) and apathy after venlafaxine XR treatment. Symptoms reduced after a switch to escitalopram, with a reduction to 50 yawns/day. Case 2: A female patient presented excessive yawning (approximately 25/day) and inability to react to environmental stressors with desvenlafaxine. Conclusion Induction of indifference and excessive yawning may be modulated by serotonergic and noradrenergic mechanisms. One proposal to unify these side effects would be enhancement of serotonin in midbrain, especially paraventricular and raphe nucleus.

Experimental procedures for the identification of material properties of intervertebal disc - a contribution for the development of biomimetic substitutes for the nucleus pulposus

Tese de Doutoramento em Engenharia Mecânica.

Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

OBJECTIVE: We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar¹, Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3% NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. METHODS: Holtzman rats were used . Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-mul volumes for 10-15 seconds. Seven days after brain surgery, water and 3% NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. RESULTS: Losartan (40 nmol) and [Sar¹, Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar¹, Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. CONCLUSION: MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested.

Influence of nucleus accumbens core or shell stimulation on early long-term potentiation in the dentate gyrus of freely moving rats

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2010

Comportamento do Heterocromossômio em alguns Ortópteros do Brasil

In the present paper the behavior of the heterochromoso-mes in the course of the meiotic divisions of the spermatocytes in 15 species of Orthoptera belonging to 6 different families was studied. The species treated and their respective chromosome numbers were: Phaneropteridae: Anaulacomera sp. - 1 - 2n = 30 + X, n +15+ X and 15. Anaulacomera sp. - 2 - 2n - 30 + X, n = 15+ X and 15. Stilpnochlora marginella - 2n = 30 + X, n = 15= X and 15. Scudderia sp. - 2n = 30 + X, n = 15+ X and 15. Posldippus citrifolius - 2n = 24 + X, n = 12+X and 12. Acrididae: Osmilia violacea - 2n = 22+X, n = 11 + X and 11. Tropinotus discoideus - 2n = 22+ X, n = 11 + X and 11. Leptysma dorsalis - 2n = 22 + X, n = 11-J-X and 11. Orphulella punctata - 2n = 22-f X, n = 11 + X and 11. Conocephalidae: Conocephalus sp. - 2n = 32 + X, n = 16 + X and 16. Proscopiidae: Cephalocoema zilkari - 2n = 16 + X, n = 8+ X and 8. Tetanorhynchus mendesi - 2n = 16 + X, n = 8+X and 8. Gryliidae: Gryllus assimilis - 2n = 28 + X, n = 14+X and 14. Gryllodes sp. - 2n = 20 + X, n = 10- + and 10. Phalangopsitidae: Endecous cavernicola - 2n = 18 +X, n = 94-X and 9. It was pointed out by the present writer that in the Orthoptera similarly to what he observed in the Hemiptera the heterochromosome in the heterocinetic division shows in the same individual indifferently precession, synchronism or succession. This lack of specificity is therefore pointed here as constituting the rule and not the exception as formerly beleaved by the students of this problem, since it occurs in all the species referred to in the present paper and probably also m those hitherto investigated. The variability in the behavior of the heterochromosome which can have any position with regard to the autosomes even in the same follicle is attributed to the fact that being rather a stationary body it retains in anaphase the place it had in metaphase. When this place is in the equator of the cell the heterochromosome will be left behind as soon as anaphase begins (succession). When, on the contrary, laying out of this plane as generally happens (precession) it will sooner be reached (synchronism) or passed by the autosomes (succession). Due to the less kinetic activity of the heterochromosome it does not orient itself at metaphase remaining where it stands with the kinetochore looking indifferently to any direction. At the end of anaphase and sometimes earlier the heterochromosome begins to show mitotic activities revealed by the division of its body. Then, responding to the influence of the nearer pole it moves to it being enclosed with the autosomes in the nucleus formed there. The position of the heterochromosome in the cell is explained in the following manner: It is well known that the heterochromosome of the Orthoptera is always at the periphery of the nucleus, just beneath the nuclear membrane. This position may be any in regard of the axis of the dividing cell, so that if one of the poles of the spindle comes to coincide with it, the heterochromosome will appear at this pole in the metaphasic figures. If, on the other hand, the angle formed by the axis of the spindle with the ray reaching the heterochromosome increases the latter will appear in planes farther and farther apart from the nearer pole until it finishes by being in the equatorial plane. In this way it is not difficult to understand precession, synchronism or succession. In the species in which the heterochromosome is very large as it generally happens in the Phaneropteridae, the positions corresponding to precession are much more frequent. This is due to the fact that the probabilities for the heterochromosome taking an intermediary position between the equator and the poles at the time the spindle is set up are much greater than otherwise. Moreover, standing always outside the spindle area it searches for a place exactly where this area is larger, that is, in the vicinity of the poles. If it comes to enter the spindle area, what has very little probability, it would be, in virtue of its size, propelled toward the pole by the nearing anaphasic plate. The cases of succession are justly those in which the heterochromosome taking a position parallelly to the spindle axis it can adjust its large body also in the equator or in its proximity. In the species provided with small heterochromosome (Gryllidae, Conocephalidae, Acrididae) succession is found much more frequently because here as in the Hemiptera (PIZA 1945) the heterochromosome can equally take equatorial or subequatorial positions, and, furthermore, when in the spindle area it does offer no sereous obstacle to the passage of the autosomes. The position of the heterochromosome at the periphery of the nucleus at different stages may be as I suppose, at least in part a question of density. The less colourability and the surface irregularities characteristic of this element may well correspond to a less degree of condensation which may influence passive movements. In one of the species studied here (Anaulacomera sp.- 1) included in the Phaneropteridae it was observed that the plasmosome is left motionless in the spindle as the autosomes move toward the poles. It passes to one of the secondary spermatocytes being not included in its nucleus. In the second division it again passes to one of the cells being cast off when the spermatid is being transformed into spermatozoon. Thus it is regularly found among the tails of the spermatozoa in different stages of development. In the opinion of the present writer, at least in some cases, corpuscles described as Golgi body's remanents are nothing more than discarded plasmosomes.

Einfluss der sportlichen Aktivität auf die motorisch-evozierten Potenziale des Musculus deltoideus und des Musculus dorsalis interosseus I

Magdeburg, Univ., Medizin. Fakultät, Diss., 2010

Charakterisierung der Projektionen des ventralen CA1 und des Subiculums zum Nucleus basomedialis der Amygdala in der Maus und ihre Beziehungen zu GABAergen Interneuronen

Universität Magdeburg, Univ., Dissertation, 2015

Discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus of the rat.

The aim of the present study was to characterize the discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the rat. In the absence of acoustic stimulation, two types of spontaneous discharge patterns were observed: units tended to fire in a bursting or in a nonbursting mode. The distribution of units in the DNLL based on spontaneous firing rate followed a rostrocaudal gradient: units with high spontaneous rates were most commonly located in the rostral part of the DNLL, whereas in the caudal part units had lower spontaneous discharge rates. The most common response pattern of DNLL units to 200 ms binaural noise bursts contained a prominent onset response followed by a lower but steady-state response and an inhibitory response in the early-off period. Thresholds of response to noise bursts were on average higher for DNLL units than for units recorded in the inferior colliculus under the same experimental conditions. The DNLL units were arranged according to a mediolateral sensitivity gradient with the lowest threshold units in the most lateral part of the nucleus. In the rat, as in other mammals, the most common DNLL binaural input type was an excitatory response to contralateral ear stimulation and inhibitory response to ipsilateral ear stimulation (EI type). Pure tone bursts were in general a more effective stimulus compared to noise bursts. Best frequency (BF) was established for 97 DNLL units and plotted according to their spatial location. The DNLL exhibits a loose tonotopic organization, where there is a concentric pattern with high BF units located in the most dorsal and ventral parts of the DNLL and lower BF units in the middle part of the nucleus.

Hypoglycemia-activated GLUT2 neurons of the nucleus tractus solitarius stimulate vagal activity and glucagon secretion.

Glucose-sensing neurons in the brainstem participate in the regulation of energy homeostasis but have been poorly characterized because of the lack of specific markers to identify them. Here we show that GLUT2-expressing neurons of the nucleus of the tractus solitarius form a distinct population of hypoglycemia-activated neurons. Their response to low glucose is mediated by reduced intracellular glucose metabolism, increased AMP-activated protein kinase activity, and closure of leak K(+) channels. These are GABAergic neurons that send projections to the vagal motor nucleus. Light-induced stimulation of channelrhodospin-expressing GLUT2 neurons in vivo led to increased parasympathetic nerve firing and glucagon secretion. Thus GLUT2 neurons of the nucleus tractus solitarius link hypoglycemia detection to counterregulatory response. These results may help identify the cause of hypoglycemia-associated autonomic failure, a major threat in the insulin treatment of diabetes.

Microautophagy of the nucleus coincides with a vacuolar diffusion barrier at nuclear-vacuolar junctions.

Nuclei bind yeast vacuoles via nucleus-vacuole (NV) junctions. Under nutrient restriction, NV junctions invaginate and release vesicles filled with nuclear material into vacuoles, resulting in piecemeal microautophagy of the nucleus (PMN). We show that the electrochemical gradient across the vacuolar membrane promotes invagination of NV junctions. Existing invaginations persist independently of the gradient, but final release of PMN vesicles requires again V-ATPase activity. We find that NV junctions form a diffusion barrier on the vacuolar membrane that excludes V-ATPase but is enriched in the VTC complex and accessible to other membrane-integral proteins. V-ATPase exclusion depends on the NV junction proteins Nvj1p,Vac8p, and the electrochemical gradient. It also depends on factors of lipid metabolism, such as the oxysterol binding protein Osh1p and the enoyl-CoA reductase Tsc13p, which are enriched in NV junctions, and on Lag1p and Fen1p. Our observations suggest that NV junctions form in two separable steps: Nvj1p and Vac8p suffice to establish contact between the two membranes. The electrochemical potential and lipid-modifying enzymes are needed to establish the vacuolar diffusion barrier, invaginate NV junctions, and form PMN vesicles.

Confirmation of functional zones within the human subthalamic nucleus: patterns of connectivity and sub-parcellation using diffusion weighted imaging.

The subthalamic nucleus (STN) is a small, glutamatergic nucleus situated in the diencephalon. A critical component of normal motor function, it has become a key target for deep brain stimulation in the treatment of Parkinson's disease. Animal studies have demonstrated the existence of three functional sub-zones but these have never been shown conclusively in humans. In this work, a data driven method with diffusion weighted imaging demonstrated that three distinct clusters exist within the human STN based on brain connectivity profiles. The STN was successfully sub-parcellated into these regions, demonstrating good correspondence with that described in the animal literature. The local connectivity of each sub-region supported the hypothesis of bilateral limbic, associative and motor regions occupying the anterior, mid and posterior portions of the nucleus respectively. This study is the first to achieve in-vivo, non-invasive anatomical parcellation of the human STN into three anatomical zones within normal diagnostic scan times, which has important future implications for deep brain stimulation surgery.

Targetting of the ventro-intermediate nucleus using ultra-high field (7T) MRI for gamma knife surgery purposes: A pilot in vivo study on healthy subjects.

INTRODUCTION: Gamma Knife surgery (GKS) is a non-invasive neurosurgical stereotactic procedure, increasingly used as an alternative to open functional procedures. This includes targeting of the ventro-intermediate nucleus of the thalamus (e.g. Vim) for tremor. We currently perform an indirect targeting, as the Vim is not visible on current 3Tesla MRI acquisitions. Our objective was to enhance anatomic imaging (aiming at refining the precision of anatomic target selection by direct visualisation) in patients treated for tremor with Vim GKS, by using high field 7T MRI. MATERIALS AND METHODSH: Five young healthy subjects were scanned on 3 (T1-w and diffusion tensor imaging) and 7T (high-resolution susceptibility weighted images (SWI)) MRI in Lausanne. All images were further integrated for the first time into the Gamma Plan Software(®) (Elekta Instruments, AB, Sweden) and co-registered (with T1 was a reference). A simulation of targeting of the Vim was done using various methods on the 3T images. Furthermore, a correlation with the position of the found target with the 7T SWI was performed. The atlas of Morel et al. (Zurich, CH) was used to confirm the findings on a detailed analysis inside/outside the Gamma Plan. RESULTS: The use of SWI provided us with a superior resolution and an improved image contrast within the basal ganglia. This allowed visualization and direct delineation of some subgroups of thalamic nuclei in vivo, including the Vim. The position of the target, as assessed on 3T, perfectly matched with the supposed one of the Vim on the SWI. Furthermore, a 3-dimensional model of the Vim-target area was created on the basis of the obtained images. CONCLUSION: This is the first report of the integration of SWI high field MRI into the LGP, aiming at the improvement of targeting validation of the Vim in tremor. The anatomical correlation between the direct visualization on 7T and the current targeting methods on 3T (e.g. quadrilatere of Guyot, histological atlases) seems to show a very good anatomical matching. Further studies are needed to validate this technique, both by improving the accuracy of the targeting of the Vim (potentially also other thalamic nuclei) and to perform clinical assessment.

Prévalence des troubles de l'humeur dans la maladie de Parkinson traitée par stimulation cérébrale profonde [Prevalence of mood disorders in Parkinson's disease patients treated with subthalamic nucleus deep brain stimulation].

Subthalamic nucleus deep brain stimulation (STN-DBS) is a recognized treatment for advanced and severe forms of Parkinson's Disease. The procedure improves motor signs and often allows a reduction of the medication. The impact of the procedure on cognitive and neuropsychiatric signs of the disease is more debated and there is an international consensus for the need of a multidisciplinary evaluation of patients undergoing such programs, including a neuropsychiatric assessment. We present a review of the literature as well as the experience at our centre focused on the short and long term outcome on mood following STN-DBS.