Aminoglycoside-induced biphasic hindlimb paralysis in the rat: a histological and electrophysiological assessment.
The intrathecal injection of gentamicin into a human patient with gram-negative bacterial meningitis as well as its intracisternal injection into rabbits caused spongy-like lesions in the gray matter and tetraplegia in rabbits. To characterize this neurotoxic effect, gentamicin was injected into the subarachnoid space of the lumbar spinal cord of the rat. A biphasic hindlimb paralysis ensued which consisted at first of a transient flaccid paralysis lasting 1 to 5 hr followed by a permanent flaccid paralysis which developed after 24 to 36 hr. The initial paralysis occurred simultaneously with the transient loss of reflex transmission through the cord but in the absence of lesions in the spinal cord or physiological alterations of neuromuscular transmission and muscle contraction. The onset of the second phase of paralysis occurred concomitant with changes in reflex transmission and appearance of lesions. Loss of neuromuscular transmission and appearance of signs of denervation (e.g., depolarization, alteration in action potential parameters, and chemosensitivity) appeared after the second phase of paralysis was established. Both the initial transient and late permanent paralysis originated in the spinal cord. The early transient paralysis appears to be due to a central block of transmission while the late paralysis apparently resulted from neuronal damage. The neurotoxic effects of aminoglycosides on neuronal elements in the spinal cord resulted in secondary effects (signs of denervation) in hindlimb muscles.
D000200:Action Potentials / Q000187:drug effects; D000617:Aminoglycosides / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D005260:Female; D005839:Gentamicins / Q000633:toxicity; D006614:Hindlimb; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D010243:Paralysis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013779:Tetrodotoxin / Q000633:toxicity
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D013779:Tetrodotoxin