Ultrastructural Signatures of Amikacin Neurotoxicity and the Protective Modulation of Memantine in Peripheral Nerves: A Transmission Electron Microscopy Exploration in Wistar Rats

Background/Objectives: Aminoglycoside antibiotics such as amikacin are indispensable for treating severe Gram-negative infections, but their clinical use is limited by a well-documented toxicity profile that has focused overwhelmingly on ototoxicity and nephrotoxicity, leaving their action on the peripheral nervous system comparatively unexplored. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist used in Alzheimer’s disease, has shown protective effects in peripheral-nerve animal models, raising the question of whether it could limit potential amikacin-induced peripheral neurotoxicity. Methods: Adult male Wistar rats were allocated to three groups: Group A: control, no drug administration; Group B: amikacin 20 mg/kg/day intraperitoneally for 14 days; and Group C: concurrent administration of amikacin 20 mg/kg/day plus memantine 10 mg/kg/day intraperitoneally for 14 days. Branches of the brachial plexus and the sciatic nerve were harvested and processed for transmission electron microscopy (TEM), and axonal, myelin and Schwann-cell ultrastructure were assessed in a blinded manner. Results: Group A showed intact axons, compact myelin sheaths and normal Schwann cells. Group B showed pronounced neurotoxic lesions: degeneration of the myelin sheath (splitting, dilation and folding), axoplasmic collapse with swollen organelles, and Schwann cells of abnormal shape. In Group C, memantine markedly attenuated the nerve fiber damage: most axons were preserved, myelin-sheath abnormalities were mild and focal, and numerous normal Schwann cells and unmyelinated nerve fibers were retained. Conclusions: Amikacin exerts a distinct, previously under-recognized ultrastructural neurotoxicity on peripheral nerves, and concurrent memantine confers substantial neuroprotection, supporting a potential adjunctive role for NMDA-receptor antagonism during aminoglycoside therapy.