A cascade is a series of events in which one event triggers the next, in a linear fashion. Thus "ischemic cascade" is actually a misnomer, since in it, events are not always linear: in some cases, they are circular, and sometimes one event can cause or be caused by multiple other events.[4] In addition, cells receiving different amounts of blood may go through different chemical processes. Despite these facts, the ischemic cascade can be generally characterized as follows:
1. Lack of oxygen causes the neuron's normal process for making ATP for energy to fail. 2. The cell switches to anaerobic metabolism, producing lactic acid. 3. ATP-reliant ion transport pumps fail, causing the cell to become depolarized, allowing ions, including calcium (Ca++), to flow into the cell. 4. The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high. 5. The presence of calcium triggers the release of the excitatory amino acid neurotransmitter glutamate. 6. Glutamate stimulates AMPA receptors and Ca++-permeable NMDA receptors, which open to allow more calcium into cells. 7. Excess calcium entry overexcites cells and causes the generation of harmful chemicals like free radicals, reactive oxygen species and calcium-dependent enzymes such as calpain, endonucleases, ATPases, and phospholipases in a process called excitotoxicity.[5][6] Calcium can also cause the release of more glutamate. 8. As the