Axonal injury in the optic nerve: a model simulating diffuse axonal injury in the brain.
A new model of traumatic axonal injury has been developed by causing a single, rapid, controlled elongation (tensile strain) in the optic nerve of the albino guinea pig. Electron microscopy demonstrates axonal swelling, axolemmal blebs, and accumulation of organelles identical to those seen in human and experimental brain injury. Quantitative morphometric studies confirm that 17% of the optic nerve axons are injured without vascular disruption, and horseradish peroxidase (HRP) studies confirm alterations in rapid axoplasmic transport at the sites of injury. Since 95% to 98% of the optic nerve fibers are crossed, studies of the cell bodies and terminal fields of injured axons can be performed in this model. Glucose utilization was increased in the retina following injury, confirming electron microscopic changes of central chromatolysis in the ganglion cells and increased metabolic activity in reaction to axonal injury. Decreased activity at the superior colliculus was demonstrated by delayed HRP arrival after injury. The model is unique because it produces axonal damage that is morphologically identical to that seen in human brain injury and does so by delivering tissue strains of the same type and magnitude that cause axonal damage in the human. The model offers the possibility of improving the understanding of traumatic damage of central nervous system (CNS) axons because it creates reproducible axonal injury in a well-defined anatomical system that obviates many of the difficulties associated with studying the complex morphology of the brain.
Gennarelli
T A
TA
Division of Neurosurgery, University of Pennsylvania, Philadelphia.
Thibault
L E
LE
Tipperman
R
R
Tomei
G
G
Sergot
R
R
Brown
M
M
Maxwell
W L
WL
Graham
D I
DI
Adams
J H
JH
Irvine
A
A
D000818:Animals; D001369:Axons / Q000293:injuries* / Q000648:ultrastructure; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D005947:Glucose / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D008959:Models, Neurological; D009900:Optic Nerve / Q000648:ultrastructure; D020221:Optic Nerve Injuries
D005947:Glucose