Abstract
Sciatic nerve injury in neonatal rats results in significant reduction in the number of surviving motoneurons and impairs muscle development. We examined the possible neuroprotective effects of daily in vivo administration of 1,4,7,8,9,10-hexahydro-9-methyl-6-nitropyrido[3,4-f]quinoxaline-2,3-dione (PNQX), an AMPA/kainate receptor antagonist, on sciatic nerve injured rats, during the period of plasticity of the rat nervous system. Furthermore, we investigated the effect of PNQX on muscle properties impaired by nerve crush. At the second postnatal day, the sciatic nerve of the rat left hind limb was crushed. Twenty-four rats were subsequently treated with PNQX and an equal number of rats, as control group, were treated with saline. PNQX was injected subcutaneously once daily (14 mg kg −1 body weight). Treatment continued until the rats were 14 days old. Measurements were then carried out to assess the contractile properties of the extensor digitorum longus (EDL), a fast-contracting muscle, and of the soleus muscle, a slow-contracting muscle, in four “age groups” of rats, each consisting of six PNQX-treated and six control animals: (a) postnatal day (P) 14, (b) postnatal day (P) 21, (c) postnatal day (P) 28 and (d) adult rats. The following parameters were recorded: number of motor units, muscle weight, maximal tetanic tension (TET 100), time to peak (TTP), half relaxation time (HRT), and fatigue index (FI). Improvement in motor unit survival after nerve injury was observed in all age groups administering PNQX. Also axotomy-induced impairment of muscle properties such as muscle weight, tension development, contraction and relaxation velocity was counteracted by injection of PNQX. The fatigue index was altered by axotomy and mostly normalized by treatment with this compound. AMPA/kainate receptor antagonists, with low toxicity, may serve in the future, as possible neuroprotective agents after acute neural injury or even as therapeutic agents in neurodegenerative diseases.
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