Abstract # 2077 Neuroprotective and antiinflammatory effects of propentofylline following a gliotoxic lesion in the rat brainstem

Abstract

Propentofylline (PPF) is a xanthine derivative that depresses activation of glial cells, whose responses induce oxidative stress and neural tissue damage during inflammation. Ethidium bromide (EB) injection into the brain causes local oligodendroglial and astrocytic loss, resulting in primary demyelination and neuroinflammation. Surviving astrocytes present increased glial fibrillary acidic protein (GFAP) expression around the injury site. This investigation aimed to evaluate the capacity of PPF of affecting glial cell behaviour during the process of demyelination-remyelination and of altering cytokine release and lipid peroxidation (measured through its byproducts TBARS or thiobarbituric acid reactive species) in the plasma and brain. Wistar rats were injected with 0.1%EB into the cisterna pontis and treated or not with PPF (12.5 mg/kg/day, intraperitoneal) during the experimental period. Brainstem sections were collected from day (D) 7 to 31 and processed for GFAP immunohistochemistry and ultrastructural investigation. A semi-quantitative method was used to compare remyelination status. Plasma and brains were also collected for TBARS and cytokines (IL-1beta and TNF-alpha, measured by ELISA). PPF treatment decreased the levels of TBARS and cytokines in plasma and brains of EB-injected rats until D15, reduced GFAP expression until D21, and increased both oligodendroglial and Schwann cell remyelination on D31. These data suggest that PPF stimulates remyelination, decreases inflammation and redox imbalances in plasma and brain and may have a preventive role in glial scar development following gliotoxic injury.