INTRODUCTION: THE CENTRAL NERVOUS SYSTEM
The central nervous system (CNS) comprises the brain and spinal cord and is the most complex organ system in the human body. The CNS differs from other organ systems in the variety of functions that it provides and in the localization of these functions to specialized areas of the CNS. The localization of specialized functions means that a relatively small, focal lesion in the CNS can produce a profound deficit, for example, loss of speech. This localization also results in the various populations of neurons within the CNS having unique capabilities and also unique vulnerabilities to disease. For example, Parkinson disease (PD) preferentially affects the neurons of the substantia nigra in the brain stem, while Alzheimer disease (AD) preferentially affects the neurons of the cerebral cortex.
CNS HISTOLOGY AND COMMON CELLULAR RESPONSES TO INJURY
Neurons (Figure 22-1) are the principal cell type within the nervous system. Acute neuronal injury is most often due to ischemia, but there are many other causes, including trauma, infections, toxic/metabolic diseases, and genetic diseases. Neurons undergoing acute cell death often show red (eosinophilic) cytoplasm and pyknotic nuclei histologically and are referred to as red neurons (Figure 22-2). Neurons may also undergo programmed cell death (apoptosis). Central chromatolysis refers to the changes that occur in the neuronal cell body (usually a lower motor neuron) when its axon is injured (axonal reaction). This axonal reaction is characterized by enlargement of the neuronal cell body, displacement of the neuron’s nucleus to the periphery of the cell body, and disappearance of the more centrally located Nissl bodies (stacks of rough endoplasmic reticulum). The more peripherally located Nissl bodies remain, hence the term central chromatolysis.
Astrocytes are a type of glial cell that provide numerous support functions for neurons. Astrocytes are somewhat analogous to fibroblasts elsewhere in the body, in that astrocytes react to injury by forming glial filaments (scar tissue). In contrast to the extracellular collagen fibers produced by fibroblasts, glial filaments are intracytoplasmic. The glial filaments immunostain for glial fibrillary acidic protein (GFAP) and highlight the star-shaped astrocytes (Figure 22-3). Gliosis (reactive astrocytosis)—the reaction of astrocytes to a brain injury—occurs in many pathologic contexts (e.g., ischemia, trauma, infection, neurodegenerative diseases, demyelinating diseases). Normally, the cytoplasm of an astrocyte is inconspicuous, so that the astrocytic nuclei appear to have no cytoplasm. However, after a brain injury, astrocytes proliferate and develop large amounts of perinuclear cytoplasm as they synthesize glial filaments. These reactive astrocytes are known as hypertrophic or “gemistocytic” astrocytes. After an injury, reactive astrocytosis becomes evident histologically after 4 days, well established after 7–10 days, and maximal at 2–3 weeks. Alzheimer type II astrocytes with enlarged, pale nuclei and inconspicuous cytoplasm develop during hyperammonemic states, such as those associated with acute liver failure or a portosystemic shunt secondary to hepatic cirrhosis. This “metabolic astrocytosis” reflects the major role of astrocytes in the detoxification of ammonium ...