Anoxic terminal negative DC-shift in human neocortical slices in vitro

Area of Science:

• Neuroscience
• Cellular Physiology
• Pathophysiology

Background:

• Anoxic terminal negativity (ATN) is a key indicator of hypoxic conditions in animal models, characterized by a negative shift in DC potential.
• This phenomenon is primarily attributed to neuronal membrane potential breakdown, but its occurrence in human neocortical neurons in vitro has been less clear.

Purpose of the Study:

• To investigate whether anoxic terminal negativity (ATN) develops in human neocortical slices subjected to hypoxia.
• To characterize the properties and recovery patterns of ATN in human brain tissue.

Main Methods:

• Human neocortical brain slices (n=15, from 13 patients) were subjected to controlled hypoxic periods (10-120 minutes).
• Direct current (DC) potential shifts, specifically ATN, were recorded.
• Evoked potentials were monitored during hypoxia and reoxygenation.
• ATN were classified based on their rise slopes (steep vs. flat).

Main Results:

• ATN were successfully observed in human neocortical slices, typically appearing as monophasic events with a latency of approximately 16 minutes.
• Two distinct types of ATN were identified: steep and flat, differing in amplitude and decay slopes.
• Repeated hypoxic episodes reduced the latency of both steep and flat ATN.
• Evoked potentials were suppressed during hypoxic DC shifts and showed incomplete recovery with extended or repeated hypoxia.

Conclusions:

• Anoxic terminal negativity (ATN) can be induced in human neocortical slices, mirroring findings in animal models.
• The characteristics and recovery of ATN suggest distinct responses and potential for neuronal damage with prolonged or repeated hypoxic insults.
• These findings contribute to understanding human neuronal responses to hypoxia and have implications for neurological conditions.