What causes oxidative stress after brain ischemia?

Recall that during ischemia, brain tissue is unable to continue aerobic metabolism due to the loss of oxygen and substrate, and ATP levels fall rapidly. This leads directly to depolarization of the neuronal plasma membrane, a surge in intracellular Ca⁺⁺, and massive release of glutamate, which, among other things, further increases intracellular Ca⁺⁺.

Both depolarization itself and the surge in intracellular Ca⁺⁺ result in the activation of phospholipases, which immediately begin to munch on the membranes. That's bad enough, but one of the by-products of this process is the release of free fatty acids (FFAs), particularly arachidonate.  

This arachidonic acid hangs out during ischemia and on into reperfusion, when oxygen gets added back into the mix. As you may recall, arachidonate is a substrate of the enzyme cyclooxygenase, which catalyzes the addition of two molecules of oxygen to a FFA, yielding prostaglandin PGG. PGG in turn is rapidly peroxidized to PGH, and in the process the species superoxide (^.O₂^-) is released.

The story so far: Generation of superoxide during brain reperfusion. Ischemia leads to a surge in intracellular calcium, which in turn activates phospholipases, which generate FFAs. During reperfusion, oxidation of FFAs leads to production of the radical species superoxide.

It's important to note superoxide is produced all the time in normal cells, and it gets soaked up by mitochondria and antioxidant enzymes and converted to water. In brain ischemia, however, an overwhelming amount of lipolysis and superoxide generation overwhelms these systems, which are under stress anyway.