Protective effects of pentoxifylline on lipopolysaccharide-induced white matter injury in a rat model of periventricular leukomalasia.

Objective: To investigate the potential neuroprotective effect of maternal pentoxifylline (PNTX) treatment in endotoxin-induced periventricular leukomalasia (PVL) in the developing rat brain.

Method: Intraperitoneal injection of lipopolysaccharide was administered on two of three Wistar pregnant rats to establish PVL. To obtain PNTX-treated group, one of the two dams were injected with PNTX. The control group was treated with saline. Rat pups were grouped as control, maternal LPS-treated group and PNTX + LPS-treated group. At 7th postnatal days, apoptosis and hypomyelination were evaluated. Apoptosis was evaluated by caspase-3 and terminal deoxynucleotidyl transferase [TdT] dUTP nick endlabelling reaction (TUNEL) immunostaining. To assess hypomyelination, myelin basic protein (MBP) staining, as a marker of myelination, was evaluated.

Results: MBP staining was significantly less and weaker in the brains of the LPS-treated group as compared with the PNTX-treated group. PNTX treatment significantly reduced the number of apoptotic cells in the periventricular WM shown on Tunel and caspase-3.

Conclusions: Presented study is first indicated that PNTX may provide protection against an LPS-induced inflammatory response and WMI in the developing rat brain. Our results also suggest that PNTX treatment in pregnant women with maternal or placental infection may minimize the risk of PVL and cerebral palsy.