MK-801 reduces retinal ganglion cell survival but improves visual performance after controlled optic nerve crush.
Excitotoxicity is implicated in secondary cell death after ischemic or traumatic brain injury. We therefore evaluated the role of excitotoxicity mediated by the NMDA glutamate receptor subtype on retinal ganglion cell (RGC) survival and visual performance after optic nerve injury in adult rats. To monitor visual deficits after mild optic nerve crush, rats were trained in a two-choice pattern discrimination task. Immediately after the crush and on postoperative day 1, MK-801 (1 nmol), a noncompetitive open channel blocker of the NMDA-receptor, was injected intraocularly. Within the first few days after crush, all rats showed a loss of their discrimination ability that was followed by a significant recovery within a 3-week testing period. Although animals treated with MK-801 had a significantly smaller initial deficit compared with 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 our 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 connected to their target. The observation that after traumatic injury MK-801 is neuroprotective functionally while being neurotoxic anatomically is a structural-functional paradox that needs to be explored further.
Schmitt
U
U
Institute of Medical Psychology, Otto-von-Guericke University, Magdeburg Medical School, Germany.
Sabel
B A
BA
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D009409:Nerve Crush; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009900:Optic Nerve / Q000473:pathology / Q000503:physiopathology*; D020221:Optic Nerve Injuries; D010364:Pattern Recognition, Visual / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology; D014785:Vision, Ocular / Q000187:drug effects*
D018696:Neuroprotective Agents; D016291:Dizocilpine Maleate