Osteopontin Attenuates Secondary Neurodegeneration in the Thalamus after Experimental Stroke.

Cortical cerebral ischemia elicits neuroinflammation as well as secondary neuronal degeneration in remote areas. Locally distinct and specific secondary neurodegeneration affecting thalamic nuclei connected to cortical areas highlights such processes. Osteopontin (OPN) is a cytokine-like glycoprotein that is excreted in high amounts after cerebral ischemia and exerts various immunomodulatory functions. We here examined putative protective effects of OPN in secondary thalamic degeneration. We subjected male Wistar rats to photothrombosis and subsequently injected OPN or placebo intracerebroventricularly. Immunohistochemical and fluorescence staining was used to detect the extent of neuronal degeneration and microglia activation. Ex vivo autoradiography with radiotracers available for human in vivo PET studies, i.e., CIS-4-[18F]Fluor-D-Proline (D-cis-[18F]FPRO), and [6-3H]thymidine ([3H]thymidine), confirmed degeneration and proliferation, respectively. We found secondary neurodegeneration in the thalamus characterized by microglial activation and neuronal loss. Neuronal loss was restricted to areas of microglial infiltration. Treatment with OPN significantly decreased neurodegeneration, inflammation and microglial proliferation. Microglia displayed morphological signs of activation without expressing markers of M1 or M2 polarization. D-CIS-[18F]FPRO-uptake mirrored attenuated degeneration in OPN-treated animals. Notably, [3H]thymidine and BrdU-staining revealed increased stem cell proliferation after treatment with OPN. The data suggest that OPN is able to ameliorate secondary neurodegeneration in thalamic nuclei. These effects can be visualized by radiotracers D-CIS-[18F]FPRO and [3H]thymidine, opening new vistas for translational studies. Graphical Abstract Intracerebroventricular injection of osteopontin attenuates thalamic degeneration after cortical ischemia (pink area). Disruption of thalamocortical connections (blue) and degeneration of thalamic nuclei (encircled) leads to microglia activation. Osteopontin protects from both neurodegeneration and microglia activation as assessed by histological analysis and autoradiograpic studies.

Estudio con tomografía por emisión de positrones de un caso de demencia vascular por hematoma talámico izquierdo, ejemplo del fenómeno de diasquisis / A study using positron emission tomography of a case of vascular dementia due to left thalamic haematoma, an example of the diaschisis phenomenon

Introducción. Las lesiones vasculares talámicas que se comportan como ictus estratégicos pueden causar amnesia, disfunciones ejecutivas o disfasia, así como síntomas comportamentales o psicológicos, y causar una demencia vascular. Caso clínico. Mujer de 58 años, hipertensa y dislipidémica, que, tras una hemorragia talámica izquierda que evolucionó radiológicamente de manera favorable, presentó un síndrome amnésico grave y otras alteraciones sutiles en la orientación y el lenguaje, dificultades en el manejo del dinero y síntomas depresivos que precisaron tratamiento ansiolítico y antidepresivo, todo lo cual fue causa de limitaciones para el normal desempeño de su trabajo. Seguida en la consulta de neurología, se le practicó una tomografía por emisión de positrones/tomografía axial computarizada con 18F-2-fluoro-2- desoxi-D-glucosa, donde se apreció un hipometabolismo en el tálamo izquierdo y, además, en la región frontal inferior ipsilateral, que se explicaría mediante el fenómeno de diasquisis. Conclusiones. El fenómeno de diasquisis es un hallazgo de neuroimagen y fisiopatológico por el cual los ictus talámicos o de los ganglios basales causan hipoperfusión/hipometabolismo en la corteza ipsilateral o contralateral, y que puede explicar síntomas a distancia corticales. El presente caso evidencia la presencia de conexiones talamocorticales, lo cual ayuda a comprender los circuitos de la memoria y a explicar la asociación en él de otros síntomas corticales, como la disfasia o las alteraciones ejecutivas (AU)

Introduction. Thalamic vascular lesions as strategic strokes can cause amnesia, executive dysfunctions or dysphasia and behavioral or psychological symptoms causing vascular dementia. Case report. A 58 years-old woman with hypertension and dyslipemia, who after a left thalamic hemorrhage with good radiological evolution, presents a severe amnesic syndrome as well as other subtle changes in orientation and in language, difficulties in managing money and depressive symptoms requiring anxiolytic and antidepressive treatment. All this joined to limitations in the normal course of her work. Followed by neurology service, a positron emission tomography with 18F- 2-fluoro-2-deoxy-D-glucose integrated with computed tomography was performed, which showed a hypometabolism in left thalamic area and also in ipsilateral inferior frontal region, explained by the diaschisis phenomenon. Conclusions. Diaschisis phenomenon is a neuroimaging and pathophysiological finding whereby thalamic or basal ganglia strokes cause hypoperfusion/hypometabolism in the ipsilateral or contralateral cortex and could explain cortical distal symptoms. This case report demonstrates the presence of thalamocortical connections, which helps to understand the circuitry of memory and help to explain the association of other cortical symptoms as dysphasia or executive dysfunction (AU)

[Thalamic pain syndrome]. / Talamik agri sendromu.

Central pain is a chronic pain due to various causes, with accompanying neurological symptoms and often unresponsive to medical therapy. Pain management and results in a 31 years old female patient with a diagnosis of thalamic pain syndrome, which is one of the causes of central pain is analysed in this article.

An 18-mer peptide fragment of prosaposin ameliorates place navigation disability, cortical infarction, and retrograde thalamic degeneration in rats with focal cerebral ischemia.

It was previously reported that prosaposin possesses neurotrophic activity that is ascribed to an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain. To evaluate the effect of the 18-mer peptide on ischemic neuronal damage, the peptide was infused in the left lateral ventricle immediately after occlusion of the left middle cerebral artery (MCA) in stroke-prone spontaneously hypertensive (SP-SH) rats. The treatment ameliorated the ischemia-induced space navigation disability and cortical infarction and prevented secondary thalamic degeneration in a dose-dependent manner. In culture experiments, treatment with the 18-mer peptide attenuated free radical-induced neuronal injury at low concentrations (0.002 to 2 pg/mL), and the peptide at higher concentrations (0.2 to 20 ng/mL) protected neurons against hypoxic insult. Furthermore, a saposin C fragment comprising the 18-mer peptide bound to synaptosomal fractions of the cerebral cortex, and this binding decreased at the 1st day after MCA occlusion and recovered to the preischemic level at the 7th day after ischemia. These findings suggest that the 18-mer peptide ameliorates neuronal damage in vivo and in vitro through binding to the functional receptor, although the cDNA encoding prosaposin receptor has not been determined yet.

Paralisis de la mirada vertical hacia abajo, trastornos de la localizacion visual, simultagnosia y ataxia optica / Downgaze paralysis, disorders of visual localization, simultagnosia and optic ataxia

Presentamos el caso de un paciente de 73 anos con un cuadro semiologico constituido por paralisis de la mirada hacia abajo, trastornos de la localizacion visual, simultagnosia y ataxia optica; analizamos desde una perspectiva anatomovascular cerebral las lesiones diagnosticadas mediante la tomografia axial computadorizada (TAC); revisamos la literatura relacionada con cada uno de los sintomas componentes del cuadro clinico; ponemos a consideracion los supuestos de que el hemisferio derecho es dominante para las funciones motrices realizadas bajo el control visual y que este complejo semiologico descrito conforma un nuevo sindrome que puede replicarse; llamamos la atencion para que se investiguen detalladamente los signos y sintomas de los pacientes con trastornos vasculares de la arteria cerebral posterior que comprometan el talamo y las estructuras vecinas.