U. Schmitt et Ba. Sabel, MK-801 REDUCES RETINAL GANGLION-CELL SURVIVAL BUT IMPROVES VISUAL PERFORMANCE AFTER CONTROLLED OPTIC-NERVE CRUSH, Journal of neurotrauma, 13(12), 1996, pp. 791-800
Excitotoxicity is implicated in secondary cell death after ischemic or
traumatic brain injury. We therefore evaluated the role of excitotoxi
city mediated by the NMDA glutamate receptor subtype on retinal gangli
on cell (RGC) survival and visual performance after optic nerve injury
in adult rats, To monitor visual deficits after mild optic nerve crus
h, rats were trained in a two-choice pattern discrimination task. Imme
diately after the crush and on postoperative day 1, MK-801 (1 nmol), a
noncompetitive open channel blocker of the NMDA-receptor, was injecte
d intraocularly. Within the first few days after crush, all rats showe
d a loss of their discrimination ability that was followed by a signif
icant recovery within a 3-week testing period, Although animals treate
d with MK-801 had a significantly smaller initial deficit compared wit
h PBS-injected controls, anatomic investigations using retrograde HRP
tracing revealed a significant retrograde loss of RGC in lesioned rats
that was significantly exacerbated by MK-801. These results confirm o
ur earlier studies suggesting that neuronal damage does not uniformly
match behavioral defects in CNS injury paradigms and that near-normal
visual performance occurs in rats with only about 10% of RGC being con
nected to their target. The observation that after traumatic injury MK
-801 is neuroprotective functionally while being neurotoxic anatomical
ly is a structural-functional paradox that needs to be explored furthe
r.