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Abstract
Objective
Energy failure and concurrent electrical silence are common features of oxygen-glucose deprivation (OGD) in the brain. Hippocampal slice has been used extensively to study electrophysiological alterations. Orthodromic extracellular field potential recording has been most widely chosen for those studies however there were few with antidromic recording. The goal of this study is to clarify which types of recordings is better for the evaluation of extent of ischecmic insults.
Methods
Rat hippocampal slices were made for the orthodromically and antidromically evoked filed potential recording. Before, during and after 6 to 11 minutes of experimental OGD, the authors measured population spike amplitude and slope of field excitatory postsynaptic potential (fEPSP).
Results
A dramatic reduction of amplitude and total disappearance of orthodromic population spike (oPS) noted 1.1 +/- 0.2 min after OGD onset. On the contrary antidromic population spike (aPS) was not affected at the beginning. It slowly and gradually diminished and finally disappeared 6.6 +/- 0.2 min after OGD onset. A transient recovery of oPS, so called hypoxic injury potentials (HIP) briefly occurred just before the total dissappearance of aPS and the both signals disappeared simultaneously. Incomplete recovery due to irreversible damage began 7 min after OGD onset. There was no recovery 10 min after OGD, 7 min after oPS loss and 2 min after aPS loss. The OGD experiments with various neuroprotective agents (MK 801, AP-5, lidocaine, CNQX, adenosine) lasted for longer than 2 min after aPS disappearance sensitively showed their efficacy.
Figures and Tables
FIGURE 1
Schematic drawing showing the experimental setup for the electrophysiological recordings from CA1 hippocampus.
FIGURE 2
A: Graph showing a representative tracing of ortho-(open circle, oPS) and anti-dromic (filled circle, aPS) population spikes before, during and after 8 minutes of oxygen-glucose deprivation. The depression of oPS noted first and a transient recovery was followed immediately before the complete dissappearance of aPS. B: Bar graph showing the relationship between the total duration of ischemia and the sequential recovery of oPS.
FIGURE 3
A: Scatter graph showing the relationship between the duration of hypoxic injury potential and the recovery of aPS. The experimental conditions that limit HIP duration to less than 1 minutes elicited poor recovery. B: Scatter graph showing the relationship between the duration of ischemia after the initial depression of oPS and the recovery of aPS. C: Scatter graph showing the relationship between the duration of ischemia lasting later the depression of aPS and the recovery of aPS.
FIGURE 4
Scatter graphs showing the effect of various neuro-protective agents and -modulators. The control data in these graphs are the same as those shown in Fig. 3C. The data point shown on the right side of two vertical dotted line and on the upper part of horizontal line means that it has some neuroprotective potentials.
TABLE 1
Result of two different recordings obtained from the same 9 min of ischemia experiments. All the agents shown to be effective in oPS recordings (20 uM MK-801, 40 uM Lidocaine) are also effective in aPS recording. In addition, those without effect in oPS recording (20 uM Lidocaine and 10 uM CNQX) are much clearer in aPS recording
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