Tese
Contribuições ao tratamento de doenças desmielinizantes: estudo experimental em ratos e retrospectivo em cães
Fecha
2013-02-26Registro en:
BECKMANN, Diego Vilibaldo. Contributions in treatment of demyelination diseases:
experimental study in rats and retrospective study in dogs. 2013. 115 f. Tese (Doutorado em Medicina Veterinária) - Universidade Federal de Santa Maria, Santa Maria, 2013.
Autor
Beckmann, Diego Vilibaldo
Institución
Resumen
Demyelinating diseases are severe owing to the destruction of myelin sheaths present in the central
(CNS) and peripheral (PNS) nervous system. The demyelination may occur in infectious and compressive
diseases of the spinal cord in dogs. The experimental model of demyelination and remyelination by
Ethidium Bromide (EB) promotes impairment of locomotor activities similar to those observed in multiple
sclerosis (MS). The purpose of this study was to investigate the effect of flavonoid quercetin on
behavioral tests, on cholinergic neurotransmission, on parameters of oxidative stress in blood, on
cholinesterase activity in blood and Acetylcholinesterase (AChE) activities in lymphocytes of rats
submitted to the EB experimental demyelination model and to review cases of the atlantoaxial subluxation
in the neurological records of the Veterinary Hospital. In the first paper, fourteen dogs were diagnosed as
affected by atlantoaxial subluxation in dogs and the condition was more frequent in toy breeds under
twenty-four month old years. The main cause found for the instability was agenesis of the odontoid
process. Clinical signs ranged from cranial cervical pain to non-ambulatory tetraparesis. The surgical
treatment demonstrated to be efficacious. The predominant time of recovery was 30-60 days after
surgery. No correlation was found between the duration of clinical signs before surgery and the time of
recovery. In the experimental study, Wistar rats were randomly distributed into four groups (20 animals
per group): Control (pontine saline injection and treatment with ethanol), Querc (pontine saline injection
and treatment with quercetin), EB (pontine 0.1% EB injection and treatment with ethanol), and EB+Querc
(pontine 0.1% EB injection and treatment with quercetin). The animals of the groups Querc and Querc +
EB were treated once daily with quercetin (50mg/kg) diluted in 25% ethanol solution (1 ml / kg) and the
animals of the control groups and EB were treated once daily with 25% ethanol solution (1 ml / kg). Two
stages were observed: phase of demyelination with a peak on day 7 and phase of remyelination with a
peak on day 21 post-inoculation of EB. In the first manuscript, the behavioral tests (the beam walking test,
foot fault test and Inclined plane test), AChE activity and lipid peroxidation in the brain structures (pons,
cerebellum, hippocampus, hypothalamus, striatum and cortex) were measured. Quercetin promoted
earlier locomotor recovery, prevented the inhibition of AChE activity and the increase of lipidic
peroxidation. In a second manuscript, parameters of oxidative stress in blood, cholinesterase activity in
blood and AChE activities in lymphocytes were measured. The experimental demyelination model by EB
promoted alteration in AChE activity of non neural cells, and also modified the oxidative stress
parameters in the blood. In addition, quercetin was able to modulate AChE activity and of the antioxidant
enzymes, as well as reduces lipid peroxidation in demyelinated rats by EB. These results may contribute
to a better understanding of the neuroprotective role of quercetin and the importance of an antioxidant
diet in humans and in animals, and the therapeutic potential this flavonoid in demyelination diseases,
such as ME in humans, distemper in dogs, as well as in spinal cord compression (atlantoaxial
subluxation).