Ait-082 and Methylprednisolone Singly, but Not in Combination, Enhance Functional and Histological Improvement after Acute Spinal Cord Injury in Rats

Abstract

Extracellular non-adenine based purines are neuroprotective. Preliminary studies indicate that administration of the synthetic purine 4–[[3–(1,6 dihydro-6-oxo-9- purine-9-yl)-1-oxypropyl] amino] benzoic acid (AIT-082, leteprinim potassium) to rats immediately after acute spinal cord injury (SCI), improves functional outcome. The effects of potential new agents are often compared to methylprednisolone (MPSS). We evaluated the effects of AIT-082 and MPSS, separately and in combination, on the functional and morphological outcome of acute SCI in adult rats. After standardized T11–12 spinal cord compression rats were given intraperitoneally one of the following: vehicle (saline); MPSS (30 mg/kg or 60 mg/kg body weight, first dose 15 min after crush); AIT-082 (60 mg/kg body weight daily, first dose 15 min after crush); or AIT-082 plus MPSS. After 1, 3, or 21 days, the rats were perfused for histological analysis. AIT-082 administrations significantly reduced locomotor impairment from 1–21 days post-operatively. At 1 and 3 days post injury, AIT-082-treatment reduced tissue swelling, tissue loss and astrogliosis at the injured cords but did not alter the extent of hemorrhage and the number of macrophages and/or microglia. MPSS reduced hemorrhage and the number of macrophages and/or microglia, but did not alter astrogliosis. At 21 days, either AIT-082 or MPSS administration improved function and morphology similarly (less tissue loss and astrogliosis). In contrast, administration of AIT-082 and MPSS together abolished the beneficial effects observed when either drug was given individually. These results suggest that MPSS and AIT-082 may exert their beneficial effects through different and potentially antagonistic pathways.

Metabolism and Distribution of Guanosine Given Intraperitoneally: Implications for Spinal Cord Injury

“…[9,13] Evaluation of Exogenous GUO Distribution GUO 8 mg/kg in saline containing tracer amounts of [8-3 H]-GUO (0.4 ug/kg; sp. act.…”

Update on emerging drugs for sarcopenia – age-related muscle wasting

“…It was reported to stimulate neurite outgrowth from PC12 cells and neurons, stimulate synthesis and/or release of neurotrophic factors from astrocytes, enhance nerve fibre regeneration in vivo and enhance memory in animals and humans [83,84] . Neotrofin has potential for treatment of spinal cord injury, ALS, age-related memory impairment, head trauma, stroke and tremor [85] .…”

Effects of a Single Dose of Methylprednisolone versus Three Doses of Rosiglitazone on Nerve Growth Factor Levels after Spinal Cord Injury

“…Methylprednisolone and rosiglitazone may improve anatomical and locomotor recovery after SCI in rodents and they have both been shown to reduce lesions 24 h after injury. 12,38 The results of the present study suggest that rosiglitazone reduces tissue damage since it significantly increased injury-induced NGF expression 24 h after injury and also increased BDNF expression after injury. Rosiglitazone and methylprednisolone exhibit anti-inflammatory effects, which reduce neutrophil and macrophage infiltration and inhibit secretion of NGF and BDNF by inflammatory cells in the early stages after injury.…”