ABSTRACT
La enfermedad de Huntington (EH) es un trastorno degenerativo hereditario que afecta a personas con predisposición genética. No existe hasta hoy un tratamiento efectivo; la enfermedad avanza lentamente y el paciente termina en incapacidad o muerte después de 15 o 20 años. Los estudios relacionados con el tratamiento de las manifestaciones clínicas que aparecen en la enfermedad, incluyen tratamientos medicamentosos y el uso de trasplante de células. En la actualidad se conoce que es posible reproducir algunas características de la enfermedad en modelos experimentales para ensayar posibles terapéuticas (ej. el modelo de lesión estriatal por inyección de ácido quinolínico; [AQ]). No se conoce el efecto restaurativo de las células de médula ósea (CMO) en este modelo. Objetivos: 1) Caracterizar morfológicamente la lesión por inyección intraestriatal de AQ. 2) Caracterizar inmunocitoquímicamente las CMO. 3) Evaluar la concentración óptima de CMO para el trasplante en el modelo y 4) Evaluar el estado funcional del trasplante de CMO, a través de la conducta motora.
Huntington Disease (HD) is a heritable neurodegenerative disease that affects people with genetic history. Until today, an effective treatment doesn't exist; the illness advances slowly and the patient finishes in inability or death after 15 or 20 years. The studies related with the treatment of the clinical manifestations, include treatments with medications and the use of cells transplant. At the present time it is known that it is possible to reproduce, some characteristics of the disease in experimental models for to use possible therapies [example: estriatal lesion of quinolínico acid; (QA)]. the restorative effect of the bone marrow cells (BMC) is not known in this model. Objectives. 1) characterizationmorphofological of the estriatal lesion whith QA. 2) to characterization immunochemical of BMC. 3) to evaluate the BMC concentration for the transplant and 4) to evaluate the functional state of BMC transplant, through the motor behavior.
Subject(s)
Huntington Disease/chemically induced , Huntington Disease/radiotherapy , Huntington Disease/blood , Huntington Disease , Bone Marrow/abnormalities , Bone Marrow/blood supplyABSTRACT
UNLABELLED: PET with [(11)C]-(R)-PK11195 is currently the modality of choice for the in vivo imaging of microglial activation in the human brain. In this work we devised a supervised clustering procedure and a new quantification methodology capable of producing binding potential (BP) estimates quantitatively comparable with those derived from plasma input with robust quantitative implementation at the pixel level. METHODS: The new methodology uses predefined kinetic classes to extract a gray matter reference tissue without specific tracer binding and devoid of spurious signals (in particular, blood pool and muscle). Kinetic classes were derived from an historical database of 12 healthy control subjects and from 3 patients with Huntington's disease. BP estimates were obtained using rank-shaping exponential spectral analysis (RS-ESA) (both plasma and reference input) and the simplified reference tissue model (SRTM). Comparison between plasma- derived BPs and those produced with the new reference methodology was performed using 6 additional healthy control subjects. Reliability of the new methodology was performed on 4 test-retest studies of patients with Alzheimer's disease. RESULTS: The new algorithm selected reference voxels in gray matter tissue avoiding regions with specific binding located, in particular, in the venous and arterial circulation. Using the new reference, BP values obtained using a plasma input and a reference input were in excellent agreement and highly correlated (r = 0.811, P < 10(-5)) when calculated with RS-ESA and less so (r = 0.507, P < 0.005) when SRTM was used. In the production of parametric maps, SRTM was used with the new reference extraction, resulting in test-retest variability (10.6%; mean ICC = 0.878) that was superior to that obtained using the previous unsupervised clustering approach (mean ICC = 0.596). CONCLUSION: Reference region modeling combined with supervised reference tissue extraction produces a robust and reproducible quantitative assessment of [(11)C]-(R)-PK11195 studies in the human brain.
