Similar Propagation of SD and Hypoxic SD-Like Depolarization in Rat Hippocampus Recorded Optically and Electrically

Abstract

Neuron membrane changes and ion redistribution during normoxic spreading depression (SD) induced, for example, by potassium injection, closely resemble those that occur during hypoxic SD-like depolarization (HSD) induced by oxygen withdrawal, but the degree to which the two phenomena are related is controversial. We used extracellular electrical recording and imaging of intrinsic optical signals in hippocampal tissue slices to compare 1) initiation and spread of these two phenomena and 2) the effects of putative gap junction blocking agents, heptanol and octanol. Both events arose focally, after which a clear advancing wave front of increased reflectance and DC shift spread along the CA1 stratum radiatum and s. oriens. The rate of spread was similar: conduction velocity of normoxic SD was 8.73 +/- 0.92 mm/min (mean +/- SE) measured electrically and 5.84 +/- 0.63 mm/min measured optically, whereas HSD showed values of 7.22 +/- 1.60 mm/min (electrical) and 6.79 +/- 0.42 mm/min (optical). When initiated in CA1, normoxic SD consistently failed to enter the CA3 region (7/7 slices) and could not be initiated by direct KC1 injection in the CA3 region (n = 3). Likewise, the hypoxic SD-like optical signal showed onset in the CA1 region and halted at the CA1/CA3 boundary (9/9 slices), but in some (4/9) slices the dentate gyrus region showed a separate onset of signal changes. Microinjection into CA1 stratum radiatum of octanol (1 mM), which when bath applied arrests the spread of normoxic SD, created a small focus that appeared to be protected from hypoxic depolarization. However, bath application of heptanol (3 mM) or octanol (2 mM) did not prevent the spread of HSD, although the onset was delayed. This suggests that, although gap junctions may be essential for the spread of normoxic SD, they may play a less important role in the spread of HSD.

Imaging Reveals the Focal Area of Spreading Depolarizations and a Variety of Hemodynamic Responses in a Rat Microembolic Stroke Model

“…26 In line with the predictions, hypoxic SDs tended to propagate B1 mm/min more rapidly than normoxic SDs as observed in brain slices. 27 These data in combination with our findings suggest that the tissue at the SD focus may be at the highest risk for permanent injury.…”

Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

“…Various pathological conditions can trigger CSD, including trauma, ischemia, and seizures (9,31). CSD also can be experimentally induced by exposure to high concentrations of excitatory amino acids or K + , direct electrical stimulation, inhibition of Na + /K + -ATPase, and energy failure (9,23,31).…”

“…CSD also can be experimentally induced by exposure to high concentrations of excitatory amino acids or K + , direct electrical stimulation, inhibition of Na + /K + -ATPase, and energy failure (9,23,31). The depolarization of a minimum critical mass of brain tissue and the presence of a critical level of extracellular K + are necessary for this induction (9).…”

Spreading Depolarization, A Pathophysiological Mechanism of Stroke and Migraine Aura

“…Among the biophysical key features of all spreading depolarizations are similar magnitudes of the ion concentration changes, the near complete sustained depolarization of the neurons with similar changes in holding current and input resistance in patch-clamped neurons, the waveform of the negative DC shift, the changes of the intrinsic optical signal, the sharp extracellular alkalotic shift followed by acidosis, the propagation in the tissue, the swelling of the neurons and shrinkage of the extracellular space, as well as the depolarization of the glial cells [7,37,[62][63][64][65].…”