Abstract
Abstract: :
Purpose: Ischemic white matter injury is common to many neurological disorders including glaucoma. A disturbance of transmembrane ionic gradients caused by depletion of cellular energy supply may play an important role. In this study, we characterized the role of intracellular Na+ overload in ischemic injury of rat optic nerves. Methods: Electrically elicited compound action potentials (CAPs) were recorded from the optic nerves acutely isolated from decapitated brown Norway rats. The nerves were superfused in recording chambers at 37o C with normal Ringer that was bubbled with 95% O2 and 5% CO2. In oxygen and glucose deprivation (OGD) experiments that simulate ischemia, O2 was replaced with N2 and glucose in the Ringers was replaced by equal molar manitol. Results: Under our conditions, robust and stable CAPs can be recorded for more than 5 hours. One hour OGD virtually eliminated the CAP (5% of control, estimated with the CAP area determined by integration of CAP amplitude over a period of 15 msec). Upon returning to normal conditions, the CAP gradually recovered. Maximum recovery (35% of control) was obtained by one hour after returning to normal oxygenated Ringer. When a rapidly reversible Na+ channel blocker, such as lidocaine (1 mM) that completely blocked the CAP under control conditions, was present during OGD, the recovery of the CAP was significantly enhanced to 65% of control. Replacing Na+ with either choline or Li+ in the Ringer during OGD also significantly reduced OGD–induced functional loss (65–70% of control). Removing Ca++ from the Ringer (plus 5 mM EGTA) provided even better preservation of the CAP following OGD (90% of control). Conclusions: Intracellular Na+ overload appears to play a significant role in ischemic injury of optic nerves. This Na+ overload induced injury seems dependent upon Ca++ influx from the extracellular space. There is also a Na+–independent injury mechanism during OGD that is mediated by Ca++ influx as well.
Keywords: ischemia • electrophysiology: non–clinical • neuro–ophthalmology: optic nerve