Differential Effects of Pentoxifylline on Learning and Memory Impairment Induced by Hypoxic-ischemic Brain Injury in Rats

Abstract

Objective Hypoxic-ischemic (HI) brain injury in the human perinatal period often leads to significant long-term neurobehavioral dysfunction in the cognitive and sensory-motor domains. Using a neonatal HI injury model (unilateral carotid ligation followed by hypoxia) in postnatal day seven rats, the present study investigated the long-term effects of HI and potential behavioral protective effect of pentoxifylline. Methods Seven-day-old rats underwent right carotid ligation, followed by hypoxia (F i O 2 = 0.08). Rats received pentoxifylline immediately after and again 2 hours after hypoxia (two doses, 60–100 mg/kg/dose), or serum physiologic. Another set of seven-day-old rats was included to sham group exposed to surgical stress but not ligated. These rats were tested for spatial learning and memory on the simple place task in the Morris water maze from postnatal days 77 to 85. Results HI rats displayed significant tissue loss in the right hippocampus, as well as severe spatial memory deficits. Low-dose treatment with pentoxifylline resulted in significant protection against both HI-induced hippocampus tissue losses and spatial memory impairments. Beneficial effects are, however, negated if pentoxifylline is administered at high dose. Conclusion These findings indicate that unilateral HI brain injury in a neonatal rodent model is associated with cognitive deficits, and that low dose pentoxifylline treatment is protective against spatial memory impairment.

Rolipram and pentoxifylline combination ameliorates experimental diabetic neuropathy through inhibition of oxidative stress and inflammatory pathways in the dorsal root ganglion neurons

“…According to previous studies, the appropriate dose of pentoxifylline 100 mg / kg was chosen. (Neves et al 2015;Halis et al 2019). In previous studies, the dose of rolipram in combination with another phosphodiesterase inhibitor was halved.…”

Insight into the Effects of High-Altitude Hypoxic Exposure on Learning and Memory

“…As increased number of people transport to high altitudes for all reasons in recent years, the effects of altitude environmental exposure on L&M cannot be ignored, and finding strategies to relief or even prevent high altitude-induced CNS disorders is thus of worthy. On the one hand, studies have found that pentoxifylline (PTX), hydrogen, and ginkgolide B can improve L&M by relieving the apoptotic damage of hippocampal neurons [ 103 , 109 , 145 ]. Salidroside analogs could improve the body's oxygen utilization and the total oxyradical scavenging capacity (TOSC) to protect brain function without significant side effects.…”

“…Both IL-1 and TNF- α receptor antagonists can attenuate the effect above. The use of pentoxifylline can significantly reduce caspase-3 activity and lighten apoptosis caused by hypoxia [ 103 ]. In addition, different regions bear different oxidative stress responses.…”

Rolipram and pentoxifylline combination ameliorates the morphological abnormalities of dorsal root ganglion neurons in experimental diabetic neuropathy by reducing mitochondrial dysfunction and apoptosis

“…We selected the doses of rolipram and pentoxifylline according to the literature, and in the case of rolipram, a lower dose was chosen due to the side effects of this drug. [ 30,31 ] Evidence showed that the dose of rolipram was halved when combined with another phosphodiesterase inhibitor. Therefore, the first we chose rolipram dose and then adjusted pentoxifylline similar dose.…”