This is the end stage of irreversible neuronal injury. In atrophy, the cell body shrinks, cytoplasm shows diffuse basophilia and nucleus becomes dark or pyknotic. Neuronal loss is recognised by the accompanying increase in glial cells (gliosis), but sometimes may need detailed quantitative analysis. Atrophy and loss are commonly seen in aging and neurodegenerative diseases.

This is recognised by the presence of ‘red neurons’- shrunken neurons with bright eosinophilic cytoplasm, dark, pyknotic nuclei and loss of nucleoli (Fig. 2.1). The red neurons are not specific to hypoxia/ischaemia, but can also be seen in hypoglycaemia and excitotoxic injury. Neurons in some locations are more vulnerable to hypoxic-ischaemic injury than others e.g. pyramidal neurons of hippocampus (Sommer sector or CA1), cortical neurons (layers 3 and 5) and cerebellar Purkinje neurons. The dead neurons may sometimes be encrusted with minerals such as calcium and iron (termed ‘ferrugination’), commonly seen in infant brains with hypoxic-ischaemic injury.

This feature is recognised by the presence of a distended neuron with pale cytoplasm, loss of Nissl substance and eccentric location of the nucleus. This change is usually seen in lower motor neurons in the brainstem and spinal cord secondary to axonal damage. A similar change in neurons referred as ‘ballooned or swollen neurons’ can be seen in a wide variety of neurodegenerative, metabolic and developmental disorders.

Accumulation of abnormal inclusions within a neuron (either in the cytoplasm or nucleus) (Fig. 2.2a–d) can be seen in various neurodegenerative diseases, metabolic diseases and viral infections (Table 2.1).