Morphological and functional analysis of an incomplete CNS fiber tract lesion: graded crush of the rat optic nerve.

Fiber tract lesions in the central nervous system (CNS) often induce delayed retrograde neuronal degeneration, a phenomenon that represents an important therapeutic challenge in clinical neurotraumatology. In the present study, we report an in vivo trauma model of graded axonal lesion of CNS neurons. Controlled by a newtonmeter device, we induced retrograde degeneration of adult rat retinal ganglion cells (RGCs) by graded crush of the optic nerve. The extent of secondary RGC death increased linearly with the applied crush force. Moreover, visually evoked potentials were used to characterize the consequences of controlled optic nerve lesion on the functional integrity of the visual projection. The presented model of fiber tract lesion closely resembles the clinical conditions of traumatic brain injury and could prove useful to screen for neuroprotective drugs based on both a morphological and functional read-out.