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Phosphodiesterase inhibition for the treatment of brain ischemia
Brazil (IFMSA Brazil) - Centro Universitario CESUMAR (UNICESUMAR), Maringa
Department of Pharmacology, Av Colombo 5790, B K68, 104a, 87020-900. Maringá, Paraná, Brazil.
Prof Dr Humberto Milani
Prof Dr Humberto Milani
English, Portuguese and Spanish
Type of Research Project
- Basic science
What is the background of the project?
Cerebral ischemia (CI), depression, post-traumatic stress disorder (PTSD), Parkinson's disease (PD) and Alzheimer's disease (AD) are among the most prevalent public health problems worldwide with a wide range of cognitive and affective impairments highly incapacitating and with high socioeconomic cost. These disorders take on alarming dimensions because of their high prevalence in the elderly as a result of increasing life expectancy, as well as the fact that pharmacological treatment options are limited and with severe and potentially serious adverse effects. In this context, phosphodiesterase inhibitors PDE-I(PDE-I)) appear as a promising therapeutic strategy for the treatment of such diseases or their symptoms, given their anti-inflammatory, antioxidant and neuroplastic properties. This study is a part of a big project aimed to investigate the effects of PDE-I in animal models of CI, with the prospect of reaching clinical trials in a second stage. In addition, the present proposal intends to integrate several levels of research involving behavioral, pharmacological, biochemical experiments.
What is the aim of the project?
The objective of this project is to test the hypothesis that phosphodiesterase inhibitors have therapeutic potential to treat CI beyond those indications for which they are already employed such as erectile dysfunction and pulmonary disease. The rationale for this proposal is based on the fact that these conditions involve aspects of neuroinflammation, neurodegeneration and changes in synaptic plasticity, in which PDEs play a prominent role.
What techniques and methods are used?
Surgeries in rodents (rats or mice) to model transient global brain ischemia. Pharmacological treatment. Behavioral analysis to evaluate functional impairments and recovery. Obtention of brain tissue for histological evalutation. Histological techniques to evaluate neurodegeneration and neuroprotection. All the data collected will be organized in Microsoft Excel tables and afterwards the results will be crossed with another studies data, analyzed to evaluate the kind of effects the procedures has made.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
It is expected from the student to take care of the animals, including feeding, cleaning, taking care of surgery wounds; to perform surgeries for brain ischemia induction along with the tutor, assisting and performing procedures on their own after learning from the tutor in the first ones; to administrate pharmacological treatments and also making filling reports created by the tutor describing possible side effects from the medication; to evaluate animals behavior in different tasks, mainly after surgery and medication administration creating reports with time, specific changes in behavior to compare the study group with control group.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes. Appropriate literature will be provided. The student will participate weekly of seminars for discussing papers and results.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster - The student’s name will be mentioned in a future publication
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
The student must be completed at least 2 years of medical school
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system
- Dézsi; L.; Kis-Varga; I.; Nagy; J.; Komlódi; Z.; Kárpáti; E. (2002). "Neuroprotective effects of vinpocetine in vivo and in vitro. Apovincaminic acid derivatives as potential therapeutic tools in ischemic stroke". Acta pharmaceutica Hungarica. 72 (2): 84–91. PMID 12498034.
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