NEUROPATHOLOGY

Author: PERAL GUTIERREZ DE CEBALLOS JOSE.
Year: 2004.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: UNIVERSIDAD COMPLUTENSE MADRID.

Summary: Approximately 80% of patients who survive a heart attack remain in a state of coma for varying periods of time. This loss of consciousness may indicate the existence of a permanent injury, evolution vegetative state, but on other occasions represents one metabolic abnormality potentially recoverable. It is important from a medical and social power to predict the intensity of damage neuro1ógico, and estimate so early prognosis of patients with encefa10patíapost-anóxica.Estudio observaciona1 prospective cohort, including all patients in coma anoxic secondary a PCR. 65 patients. Average age 59 years. APACHE II 28.7. Average stay 9.7. Mortality to 6 months 81%. Evolution neuro1ógica to 6 months: 57 patients in a coma, 5 with good recovery and 3 with moderate disability. The presence of mioclonías, the pattern "Burst-Suppression" in the EEG tracing and the absence bilateral N20 imply evolution e5tado vegetative at 100% of our patients. The initial clinical examination allows a first approach to the clinical situation, but it lacks sufficient weight to allow decisions on the discontinuity of treatment. The abolition of reflection fotomotor or lack of any response motor may not mean lesion irreversible and therefore the withdrawal of supportive measures should be questioned. The absence bilateral N20 is the most useful tool for establishing the poor prognosis of encefa10patía post-anóxica. Potential somatosensory not allow predict or recoverability good evolution of these patients

Author: LÁZCOZ RIPOLL PAULA.
Year: 2004.
University: NAVARRA.
Place of defense: DEPARTAMENTO DE CIENCIAS DE LA SALUD.
Place of preparation: UNIVERSIDAD PÚBLICA DE NAVARRA.

Summary: INTRODUCTION tumors neuroblásticos are malignant solid tumors more common during the age pediátrica.Según the International Committee of Pathology Neuroblastoma distinguishes four types of tumors neuroblástcos: neuroblastoma, ganglioneuroblastomas intermezclado, ganglioneuroblasoma modular and ganlioneroma.Las alteraiones most frequent genetic frecuenates in these tumors are the extension of MYCN and deletions in 1p, both associated with more forecast. GOALS - Determine the frequency of deletions and microsatellite instability in 10q and 3p21 - Analysis degree of hypermethylation of the gener PTEN, MGMT, MX11, FGFR2, RASSF1A, NORE1A, BLU And CASP8 and its correlation with the level of gene expression . - Determinacción of gains and losses of genetic material at a global level. - Determine the correlation between the artifacts found and data from clinical pathological tumors. MATERIALS AND METHODS. The study was conducted on 45 tumors neuroblásticos and 12 cell lines neuroblastoma. The techniques used were as follows: differential PCR, PCR, MSP, RT-PCR and CGH. RESULTS. There were deletions and microsatellite instability in 10q and 3p21 much as 21% of the samples analizadas.Los gene MGMT, RASSF1A, NORE1A, BLU and CASP8 found hipermetilados in an 8%, 83%, 3%, 8% and 60 % of the tumors analyzed, and by 25%, 100%, 50%, 66% and 92% of the cell lines detected neuroblastoma.Se absence of expression of RASSF1A in all cell lines and were gains of chromosomes 17 and 2 p, the loss of chromosomes 22 and 11 and the expansion of MYCN. CONCLUSIONS The most important conclusions drawn from this study were as follows: 1. The alterations at the level of chromosome 10q appears to be a type of alteration uncommon in these tumors, while the region altered chromosome 3p21 appears more frequently. 2. There was a statistically significant relationship between the hypermethylation of RASSF1A and CASP8 which suggests the need to alter both the Brakes on poliferación cell as the induction of apoptosis may be created for a tumor neuroblástico. 3. We did not find any statistically significant relationship between genetic alterations found and data clinico-patológicos of tumors.

Author: TERESA PARREÑO LUIS JULIO JOSE DE.
Year: 2004.
University: PAÍS VASCO.
Place of defense: FACULTAD DE MEDICINA Y ODONTOLOGIA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: A case control study was performed in 147 patients to determine the prevalence of impaired nerve conduction at the central level and assess whether it is independent of the peripheral alterations. In diabetic patients there is increased latencies of the waves LIyL III and latencies interpicos III, IV, V and in diabetic patients which involves changes in measures of the central and peripheral conduction. This correlation between alterations in peripheral and central suggests the existence of a common pathogenic mechanism. The relationship between the findings of PESS and the presence of NP shows that association between the presence of peripheral neuropathy and peripheral proximal marker driving. In diabetic patients, there is a disruption of nerve conduction at midfield and troncoencefálico that correlates with changes in nerve conduction at peripheral level, and there is also an effect of the auditory afferent pathways both peripheral as troncoencefálico. The microangiopathy markers correlates with altered nerve conduction at troncoencefálico showing a common pathogenic mechanism and microangiopathy believe that this could prejudge a change in the mechanisms of nerve conduction both troncoencefálico as cerebral microvascular factors playing an important role in the chronic neurological complications of diabetes. Instead we found no association between time evolution dyslipidemia, hypertension, and so on. Central and neuropathy. The prevalence of carpal tunnel syndrome associated in a significant way to diabetes 21.4% in diabetics compared with 2.6% in controls and the same is repeated with peripheral neuropathy 50.1% in diabetics compared with 2% in controls .

Author: Pérez Asensio Fernando Jesús.
Year: 2004.
University: VALENCIA.
Place of defense: Facultad de Ciencias Biológicas.
Place of preparation: Facultad de Medicina - Universitat de València.

Summary: The acute stroke ( "stroke" brain) are neurological disorders caused by the sharp decline of cerebral blood input ( "cerebral ischemia"). The incidence of stroke in Spain is about 200 cases per 100,000 population, which stands as the second leading cause of death, as well as the leading cause of permanent disability and the second of dementia. Except for the application of thrombolytic therapy, there is currently no other effective treatment of stroke in clinic. The rationale behind the proposals neuroprotective therapy in this study is to prevent or limit pharmacologically succession deleterious cellular reactions triggered by ischemia and reperfusion just leading to the cells to death, especially those in the darkness and who are capable of be rescued. The outcome of this study is therefore to evaluate the potential neuroprotective of certain substances capable of interfering on three pathophysiological mechanisms involved in the brain damage caused by ischemia: NO, oxidative stress and inflammation. Given the importance of the experimental model in studies of neuroprotection, previously characterized the model of transient focal cerebral ischemia in rats induced by cerebral artery occlusion half through "technique intraluminal suturing." During the experiments was monitored infusion cerebro-cortical (TPP) by láser-Doppler in an area of ischemic penumbra, systemic blood pressure (SBP), the pO2 and pCO2, and the pH and blood glucose in the blood. Finally it was determined the neurological impairment and cerebral infarct size resulting. OBJECTIVES: 1 - The first specific objective was to assess the hypothesis that NO produced by the enzyme inducible nitric oxide synthase (iNOS) after ischemia caused by late fall in the levels of ATP, which in turn causes the release late glutamate. This sequence could contribute to the progression of heart attack, and thus inhibitors may prove beneficial in the treatment of cerebral ischemia. It used the selective iNOS inhibitor, 1400W. 2 - The second specific goal was to assess the hypothesis that cerebral ischemia eliminates the glutathione peroxidase activity in the ischemic tissue and reduces therefore endogenous antioxidant capacity. Therefore, the recovery of glutathione peroxidase activity by the administration of drugs mimicking their antioxidant activity, it could have a beneficial effect on ischemic brain damage. It used the antioxidant seleno-orgánico, ebselén. 3 - The third and final objective was to assess the hypothesis that the fosfolipasas A2 secretion (sPLA2s) are involved in the pathophysiology of ischemic brain damage by their participation in the development of the inflammatory response, and therefore their inhibition could impact neuroprotective. It used the selective inhibitor of sPLA2s, 12-epi-scalaradial. CONCLUSIONS 1-occlusion transient cerebral artery half (90 min of ischemia / 3 days of reperfusion) induces the expression of iNOS in the brain and late overproduction of NO, a phenomenon that in turn half of ATP depletion and release glutamate. The neuroprotective effect of 1400W (2.5 mg / kg / h, intraperitoneally) confirmed that the production of NO from the iNOS contributes to the damage caused by cerebral ischemia as well as the potential usefulness of the determination of L-arginine and L-glutamato plasma as markers of the damage caused by ischemia / reperfusion. 2 - The administration of ebselén in single dose (100 mg / kg) did not reduce the size of myocardial ischemia resulting from a severe (2 h of isque 8 mia / 7554 days of reperfusion), although seen a slight preservation of perfusion intraisquémica, which contrast with the results obtained in previous studies conducted with isquemias less severe and shorter survival times. the affected tissue. These results suggest that at least some isoforms of sPLA2s might have a neuroprotective effect in cerebral ischemia, and therefore its inhibition prove deleterious to the ischemic brain tissue.

Author: SOLÉ TOST SONIA.
Year: 2004.
University: BARCELONA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: CSIC-IIBB -IDIBRAS.

Author: Morote García Julio César.
Year: 2005.
University: MURCIA.
Place of defense: Facultad de Química.
Place of preparation: Facultades de Biología y Veterinaria.

Author: SABATÉ MARTÍNEZ M. DEL MAR.
Year: 2005.
University: ROVIRA I VIRGILI.
Place of defense: F.MEDICINA CIÈNCIES SALUT.
Place of preparation: FACULTAT DE MEDICINA I CIÈNCIES DE LA SALUT.

Author: PÉREZ CAPOTE KAMIL.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Unknown signal that triggers glial activation in response to neuronal injury, but it is suggested that alterations in contacts neurona-glía as the presence of certain soluble factors secreted by the damaged neurons may play an important role in this process. This paper elaborated on knowledge of the role of glía in response to neuronal injury and glial activation process triggered by two models of neuronal death: neuronal death by excitotoxicidad by high concentrations of glutamate and neuronal death by apoptosis through K + deprivation of culture medium. It has been found that the glial cells of the cerebellum crops neurona-glía to respond to the damage to neuronal functional changes associated with glial activation, as occurs in vivo. However, although the two experimental models of neuronal damage used (excitotoxicidad and apoptosis) death occurs in the majority of neurons to 24, there are differences in neuronal death induced. In response to neuronal death by exitotoxicidad in glial cells or hay production factors related to activation of a response proinflamatoria, increase their proliferation and phagocytic activity. In response to neuronal death by apoptosis glial cells do not produce proinflammatory molecules or proliferate, but their phagocytic activity triggering more quickly than in the model excitotoxicidad. In this case, the glial activation is restricted to the detection and removal of damaged neurons without producing factors that may amplify the glial activation and transform it into harmful. The results show that the state faced glial cells may have an important role in the neural response to noxious stimuli. This could be very important for designing strategies to enhance those protective properties of the activated glial cells or inhibit those that are harmful to the neurons, with the aim of promoting the mechanisms of neuroprotection harmful to a particular stimulus.

Author: MASI LATIFA.
Year: 2005.
University: SEVILLA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE BIOLOGÍA.

Author: GARCÍA CABEZAS MIGUEL ÁNGEL.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The thalamus of the primates receiving multiple aferencias modulating different biochemical nature. Among them, the dopaminergic innervation is one of the most discussed and least studied, although there are multiple data dispensers in the literature suggest that the presence of this innervation in the thalamus of the primates. The objectives of this thesis have been to demonstrate this innervation studying their distribution and their microscopic characteristics. It has sought to give a practical work offering maps of the dopaminergic innervation of the thalamus monkey and the man who could be used in clinical and experimental studies bulls. The methods used have been histochemical techniques (Nissl, Gallyas) histoenzimáticas (acetylcholinesterase, citocromo-oxidasa) Immunohistochemical and brain tissue of macaque monkey and human obtained postmortem. The axones dopamine were found inmunohistoquímicamente with antibodies against the conveyor opamina, which is a marker specific antibodies against the dopamine transporter, which is a specific marker of dopaminergic phenotype. The mapping of the distribution of these axones have been developed with software Neurolucida and Canvas. The thalamus of the primates receive a wealth of dopaminergic innervation expressing transporter and dopamine, which is distributed in heterogeneous manner by all nuclei talámicos. The nuclei of thalamus macaque monkey receiving an innervation are more dense nuclei associative dorsomediano and lateral and posterior nuclei engines ventales VPLo and VLc. In the thalamus human innervation is more dense in kernels associative dorsomediano and lateral later kernels engines ventales earlier and in some nuclei límbicos of the median line. Of the afferent and efferent connections of these nuclei, it appears that the dopaminergic system talámico is in a key position to modulate higher functions, which depend on communication between barks, and complex circuits subcórtico-tálamo- subcorticales or subcórtico-tálamo-corticales character limbic, sensory and motor. The loss or dysfunction of the dopaminergic neuromodulation in the thalamus of the primates may be the substrate pathophysiologic symptoms of some diseases due to injury or dysfunction of the dopaminergic systems such as Parkinson's disease, schizophrenia or addiction to certain drugs.

Author: TORNERO PRIETO DANIEL.
Year: 2006.
University: CASTILLA-LA MANCHA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The permeabilización of mitochondrial membranes is a process seen as a point of no return in the apoptotic signaling pathways responsible for a large number of diseases that affect the nervous system particularly as ischemia, aging and certain neurodegenerative diseases. In this paper we study processes that occur during the permeabilización of the mitochondrial inner membrane in response to two stimuli such as the increase in the levels of intracellular calcium and accumulation of reactive oxygen species responsible for the so-called oxidative stress. Through electrophysiological techniques, microfluorimétricas and biochemical processes are studied as the activation of Conductance Multiple Channel, the loss of mitochondrial potential, the swelling of the mitochondrial matrix, the release of cytochrome c to the cytoplasm and the activation of the cascade of caspases. In addition, we studied the role of the protein anti-apoptótica the family of Bcl-2, Bcl-xL, in the regulation of these processes, revealing its inhibitory function of this protein mitochondrial on them. Finally, it was found damage caused by reactive oxygen species on the activity of two enzymes essential cellular energy metabolism, such as gliceraldehído 3-fosfato dehydrogenase and citrate synthase.

Author: FAIZ MARYAM.
Year: 2006.
University: AUTÓNOMA DE BARCELONA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The mammalian brain retains actively proliferating progenitor cells and quiescent stem cells in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus. Normally, these cells generate new neurons that migrate 1) from the SVZ through the rostral migratory stream to the olfactory bulb and differentiate into interneurons and 2) from the SGZ to the granule cell layer of the dentate gyrus. Brain damage induces neurogenesis in various experimental paradigms and raises the possibility of cell replacement from endogenous neural stem cells. The difficulty with these studies is that most often neurogenesis is defined in terms of 5´Bromodeoxyuridine (BrdU) incorporation and the differentiation of BrdU+ cells into neurons. In the context of injury, a progenitor response would not only have to include proliferation, but also survival, differentiation, migration and integration into damaged tissue to provide a therapeutic outlook for brain regeneration. The immature brain responds uniquely to injury; there is increased plasticity and improved outcome and a greater capacity for neurogenesis than the adult brain. However, few studies have been done on the immature brain and surprisingly little is known about the contribution of progenitor pools in recovery from immature brain damage. An understanding of the immature environment that is more permissive and shows increased plasticity may provide crucial insight into the underlying mechanisms of the precursor response in the mature central nervous system (CNS). The principal objective of this thesis was to understand the proliferation and migration dynamics of progenitor cells after damage to the developing brain and subsequent determination of whether these cells were able to mature and integrate into the damaged tissue. Mechanisms used by neural progenitor and stem cells for survival and migration were also investigated. A model of neonatal rat excitotoxicity was used in order to characterise the endogenous progenitor cell response to immature brain damage; Long Evans postnatal rat pups were stereotaxically injected with either N-methyl-D-aspartate (NMDA) or saline in the right sensorimotor cortex. In order to examine the pattern and time course of proliferating cells in the brain, NMDA injected, saline injected and intact controls were pulse labeled with BrdU. In order to trace the migration of VZ/SVZ cells after brain insult, Cell Tracker Green (CTG) was injected into the right lateral ventricle four hours before lesioning with NMDA and used as a tracer of SVZ cells. The identity of cells and protein expression was visualized by immunohistochemistry. To determine if CTG+ SVZ cells were capable of integrating into the appropriate cortical neuronal circuits, Fluorogold was injected into the internal capsule. Guidance molecules were analyzed and confirmation of migration strategies was done using semi-thin sections. Analysis of the germinative niches in control animals showed peak proliferation at postnatal day 12 that decreased in the adult. Heterogeneous expression of Cu/Zn superoxide dismutase (Cu/Zn SOD) in the germinative zones was observed experimentally; and Cu/Zn SOD was proposed as a mechanism for coping with oxidative stress and increased energy requirements by neuronal lineage progenitors in the developing brain. Contrary to the adult case, neonatal cortical excitotoxicity caused a decrease in proliferation in the SVZ and a later appearance of proliferating striatal groups. This was the first study to demonstrate that excitotoxic injury to the neonatal rat brain results in sustained migration of SVZ precursor cells into areas of primary and secondary neurodegeneration. Progenitors used strategies for migration and mobilization that recapitulate development, which include radial-glial-like guides and roundabout 1 (Robo1) and chemokine receptor 4 (CXCR4) mediated signalling. Differentiation studies showed that some SVZ progenitors become mature neurons in terms of their morphology and protein expression, but that there is very little axon extension (suggestive of integration) of new neurons into the existing 8 circuit 3f5 ry. In summary, this work describes the four major aspects of the progenitor cell response to immature excitotoxic brain damage. Understanding the dynamics of progenitor cells in the germinative zones of the developing brain in both normal and pathological states is key in harnessing the therapeutic potential that this endogenous population may provide.

Author: TORNERO PRIETO DANIEL.
Year: 2006.
University: CASTILLA-LA MANCHA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The permeabilización of mitochondrial membranes is a process seen as a point of no return in the apoptotic signaling pathways responsible for a large number of diseases that affect the nervous system particularly as ischemia, aging and certain neurodegenerative diseases. In this paper we study processes that occur during the permeabilización of the mitochondrial inner membrane in response to two stimuli such as the increase in the levels of intracellular calcium and accumulation of reactive oxygen species responsible for the so-called oxidative stress. Through electrophysiological techniques, microfluorimétricas and biochemical processes are studied as the activation of Conductance Multiple Channel, the loss of mitochondrial potential, the swelling of the mitochondrial matrix, the release of cytochrome c to the cytoplasm and the activation of the cascade of caspases. In addition, we studied the role of the protein anti-apoptótica the family of Bcl-2, Bcl-xL, in the regulation of these processes, revealing its inhibitory function of this protein mitochondrial on them. Finally, it was found damage caused by reactive oxygen species on the activity of two enzymes essential cellular energy metabolism, such as gliceraldehído 3-fosfato dehydrogenase and citrate synthase.