Brain, Neuron - Degeneration

It is important for the pathologist to be aware of the various forms of subtle early changes associated with neuronal injury. These types of neuronal changes may be evident in animals receiving lower doses of the test compound, or in nuclei of the brain less vulnerable to the agent from higher dosed animals. Injury to neural tissue may involve one or more modes, such as vascular injury in which fluid accumulates in the neuropil, creating a vacuolated appearance of the region. Direct neuronal injury may involve the membrane and ion and fluid transfer, in which case vacuoles may become evident in the neuronal perikaryon. Commonly, the injury involves metabolic processes, particularly disturbances to neuronal energy production, in which case cell death occurs characterized by central chromatolysis, neuronal necrosis, and ultimately lysis. Figure 1, Figure 2, and Figure 3, at low and higher magnification, depict degeneration of internal granule cells of the olfactory bulb. Note that the change in Figure Figure 1 is worse on one olfactory bulb (arrow), with degeneration and loss of neurons, as well as rarification of the entire bulb structure. The contralateral olfactory bulb is divided from its affected counterpart by a thin osseous plate, and the posterior portion of the olfactory mucosa is present ventrally. The structure of the contralateral olfactory bulb provides a good comparison in Figure 1 and Figure 2, having a normal glomerular layer, external plexiform layer, and internal granule cell layers. Close observation of the olfactory bulb for lesions is important in toxicologic studies, even if the compound is not delivered by the inhalation route. The necrotic and degenerative changes of granule cells of the olfactory bulb have a morphology similar to that seen in granule neurons in other sites, such as the granular cell layer of the cerebellum.

Figure 4 and Figure 5 depict a commonly overlooked subtle and early form of neuronal injury known as “granulovacuolar change.” The perikaryon is slightly swollen and contains small vacuoles and granularity (arrowheads), suggesting membrane injury and distension of the cytoplasmic organelles such as the endoplasmic reticulum and mitochondria. In these images, it is accompanied by other ancillary evidence of neuronal injury, such as central chromatolysis (black arrows) and genuine basophilic “chronic” nerve cell change (white arrows). Various stages of neuronal and astrocytic degeneration as documented by light and electron microscopy are available in a sequenced study by Cavanagh et al. (1998) of the effects of a mycotoxin on the rat cerebellum.