Banca de DEFESA: Miguel Cesar Merino Ruiz

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Miguel Cesar Merino Ruiz
DATE: 19/07/2024
TIME: 09:00
LOCAL: Plataforma Virtual ZOOM - https://us06web.zoom.us/j/84891932097? pwd=3PSvhA7di7ViGOMUaiykU5Lgt
TITLE:

Early Deep Brain Stimulation in the Model of Parkinson's Disease Induced by Intraestriatal Infusion of 6-Hydroxydopamine in Mice

KEY WORDS:

Neuroprotection; DBS; Parkinson's disease; Rodent; 6-OHDA.

PAGES: 100
BIG AREA: Outra
AREA: Defesa
SUMMARY:

Introduction: Deep brain stimulation (DBS) of brain nuclei is an effective symptomatic therapeutic strategy for the treatment of Parkinson's disease (PD). Unlike humans, there is evidence of neuroprotection mediated by DBS in rodents where parkinsonism was experimentally triggered, but in protocols conducted outside the acute phase of the disease induction. Objectives: To study neuroprotection as well as motor responses induced by DBS in the acute phase of parkinsonism induction through intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA) in mice. Materials and Methods: Three experimental groups were defined. The first two groups received interventions only on the left side of the brain, preserving the right side for control. One group underwent a nigrostriatal lesion and had an activated intracerebral DBS electrode implanted to neuromodulate the left Subthalamic Nucleus (STN) (6-OHDA + DBS) (n=6); another had a nigrostriatal lesion and an inactive DBS electrode implanted in the same location (6-OHDA) (n=8); and the remaining group was Naive (n=5). The interventions were performed on day zero (D0). During the first four days after the procedure (D1 to D4), behavioral assessments and the measurement of electrical resistance of the brain-electrode system in the 6-OHDA + DBS group were carried out. Body mass was measured in the animals from D1 to D4 as well as on D7, just before euthanasia for collection and subsequent analysis of the animals' brains. After Nissl staining of the STN region, animals with inaccurately located electrodes were discarded. An immunohistochemical study was carried out with Tyrosine Hydroxylase (TH) staining in the sections of the Substantia Nigra (SN) and the striatum to quantify the difference in the number of nigral dopaminergic neurons as well as the density of striatal dopaminergic terminals between lesioned and intact side Results: When comparing parkinsonian animals, those that underwent DBS regained body mass and exhibited improved performance in behavioral tests. While there was a trend towards a reduction in electrical resistance of the brain-electrode system, it was not statistically significant. More TH+ cells were identified in the SN ipsilateral to the lesioned side, particularly in the central and lateral regions. Additionally, a higher optical density of TH staining was observed in the lesioned striatum sections of the animals that received DBS. Conclusion: Despite the deteriorated clinical condition of the animals in the acute post-parkinsonism induction phase, the presented data show a body mass gain, favorable motor effect, reduced loss of striatal dopaminergic terminals, as well as a compartmentalized neuroprotective effect in the STN of mice that received four days of DBS, initiated one day after the induction of parkinsonism by 6-OHDA, compared to those that did not receive it. In the current context of seeking diagnosis of PD in premotor stages, the findings contribute to enriching the discussion on neuroprotective therapeutic strategies, proposing invasive neuromodulation as a potential therapeutic approach in an appropriate context.

COMMITTEE MEMBERS:
Externa à Instituição - ALESSANDRA MUSSI RIBEIRO - UNIFESP
Externa à Instituição - ANDREIA BIOLCHI MAYER - UNIPLAC
Externo à Instituição - GABRIEL AVOHAY ALVES CAMPOS - OUTROS
Presidente - 2567703 - MARCIA RENATA MORTARI
Interna - 1562111 - PEROLA DE OLIVEIRA MAGALHAES DIAS BATISTA