Mechanisms of Neuron Death (Necrosis, Apoptosis, Autophagy) After Brain Ischemia

Necrosis

Necrotic cell death or necrosis is an accidental type of cell death in living tissue and always caused by pathological factors, such as energy failure after brain ischemia. Cell death due to necrosis is always passive, and thus does not need activation of a particular cellular signaling pathway. A typical necrotic process due to brain ischemia encompasses swelling of the cell and subcellular organelles, followed by multiple organelle damage, the loss of cell membrane integrity, and an uncontrolled release of cellular contents into the surrounding extracellular space ( Fig. 43.1 ). As a result, necrosis usually initiates an inflammatory response in the surrounding areas of cell injury, which may be contained locally. However, severe necrosis may also lead to systemic inflammation in the remote organs, such as thymus, spleen, and small and large intestines. The systemic inflammatory response may be mediated by the circulating inflammatory signals, such as damage-associated molecular pattern molecules released from necrotic cell or tissue. Untreated necrosis can lead to a buildup of decomposing dead tissue and cell debris at or near the site of the cell death, resulting in tissue infarction.