Propentofylline reduces glial scar development following gliotoxic damage in the rat brainstem

Abstract

Propentofylline is a xanthine derivative that depresses activation of glial cells, whose responses contribute to neural tissue damage during inflammation. Ethidium bromide injection into the central nervous system induces local oligodendroglial and astrocytic loss, resulting in primary demyelination, neuroinflammation and blood-brain barrier disruption. Surviving astrocytes present a vigorous reaction around the injury site with increased immunoreactivity to glial fibrillary acidic protein (GFAP). Objective This study aimed to evaluate the effect of propentofylline administration on astrocytic response following gliotoxic injury. Method Wistar rats were injected with ethidium bromide into the cisterna pontis and treated or not with propentofylline (12.5mg/kg/day, intraperitoneal) during the experimental period. Brainstem sections were collected from 15 to 31 days after gliotoxic injection and processed for GFAP immunohistochemistry. Results and Conclusion Results demonstrate that propentofylline decreased astrocytic activation until the 21st day, suggesting that this drug may have a role in reducing glial scar development following injury.

Propentofylline decreases hypothalamic astrogliosis induced by hypercaloric diet in the rat

“…A strengthening of the cAMP signaling, which can be achieved by adenosine agonists and by PPF, stimulates the production of trophic factors in astrocytes, apparently preventing a deleterious and secondary astrocytic activation caused by previous microglial upregulation. Although not entirely understood, it has been accepted that drugs that elevate extracellular adenosine and/or block the degradation of cyclic nucleotides, like PPF, may be used to counteract glia-related damage in CNS pathological processes 22,29,30 .…”

“…It probably depresses activation of microglial cells and astrocytes, which is associated with neuronal damage during inflammation and hypoxia, and consequently decreases glial production and release of damaging proinflammatory factors 17 . It has previously been seen that PPF decreased the peripheral astrogliosis observed following gliotoxic injury in the rat brainstem 22 .…”

Integrative Nutritional Therapy in Canine Cognitive Dysfunction

“…20,33 Propentofylline, a xanthine derivative, increases the molecular signal adenosine and is helpful in suppressing the release of microglial inflammatory mediators and free radicals. 34,35 It is used in treating dullness, lethargy and depression in CCD. 20,36 The minimal data on side effects includes increased body weight and decreased exploratory behavior in an animal model.…”

Síndrome da disfunção cognitiva canina: revisão de literatura

“…Já a nicergolina melhora a utilização da glicose pelo cérebro, eleva a biossíntese de ácidos nucleicos e proteínas, além de possuir ação em sistemas de neurotransmissão. Fármacos como adrafinil e modafinil também estão sendo propostos devido a sua ação potencializadora no sistema noradrenérgico (Azkona et al, 2005;Gallego et al, 2010;Bondan et al, 2016). No entanto, ao instituir o tratamento para SDC em cães, deve-se considerar o estado de saúde geral do paciente, assim como a utilização de outras medicações já administradas ao animal, pois estes fármacos podem causar efeitos adversos ou interações medicamentosas, colocando em risco o tratamento ou a vida do paciente (Landsberg et al, 2011).…”