Excitotoxic Injury

Glutamate Signalling

The brain's main excitatory signal. Everything fast the brain does runs on it, and too much of it is how neurons die. Long-term users show a chemical signature consistent with raised turnover, which is the nearest thing to direct human evidence of a neurotoxic process in this literature.

Hippocampus

Where new memory is laid down. Unusually sensitive to sustained cortisol and to lost deep sleep, both of which these compounds can produce, which makes it the structure behind most reported memory complaints.

NMDA Glutamate Receptor

The receptor that carries the calcium current behind learning. It is also the route by which too much glutamate kills the cell, so the same channel that writes memory is the one that destroys the neuron when it stays open too long.

Astrocyte

The support cell that feeds neurons and clears glutamate from the synapse. It also expresses aromatase, which means part of the brain's own estrogen supply comes from glia.

Mitochondrial Calcium Buffering

How much calcium a neuron's mitochondria can absorb before the cell dies. This is the single most underrated number in the whole estrogen argument: estradiol does not stop calcium entering the neuron, it raises the amount the neuron can survive.

Neuronal Apoptosis

Programmed neuron death. Unlike muscle, these cells are largely not replaced, so this process is where a reversible effect becomes a permanent one. Everything protective in this module ultimately resolves to whether it raises or lowers this.