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Neuronal damage and neuronal changes

  1. Gastroepato
  2. Neurology
  3. Neuronal damage and neuronal changes
  4. Coma
  5. Metabolic coma
  6. The brain decay

notes by dr Claudio Italiano

What is neuronal damage?

Neuronal damage can be an acute process, e.g. determined by a stroke, which always derives from the suffering of the nerve cell, consequence of depletion of oxygen or glucose due to vascular events, in the sense that the cerebral circulation is interrupted either by an ischemic or hemorrhagic block of the same; in other cases it is a brain trauma, or a slower process, often associated with accumulation of abnormal protein aggregates, as occurs in degenerative brain disorders.

Neurons require a continuous supply of oxygen and glucose to meet the metabolic needs.
This fulfills the physiological and anatomical needs of the cells, including the maintenance of membrane gradients, which are essential for action potentials, and the support of the cytoplasmic extension of the dendritic arborization of neurons and axons, which can extend to a large distance from the cell body (over 1 m in adults).

Since most mature neurons are maintained throughout an individual's life span, protein turnover and quality must be precisely regulated to ensure cellular integration. It is not surprising that many neurological diseases derive from the harmful effects due to the accumulation of proteins with a conformational defect (proteinopathy).

Morphology of damaged neurons

Acute neuronal damage ("red neuron"): refers to a spectrum of alterations, related to hypoxia / acute CNS ischemia or other acute insults, which constitute the first morphological indicators of neuronal cell death.

The "red neurons" are observed after about 12-24 hours from the irreversible hypoxic / ischemic insult. The morphological characteristics are constituted by a contraction of the cell body, nucleus pycnosis, disappearance of the nucleolus and loss of the substance of Nissl, with intense eosinophilia of the cytoplasm.

Types of damage to the neuron

Subacute and chronic neuronal damage ("degeneration"): s refers to neuronal death that manifests itself in long-lasting progressive neurodegenerative diseases, characterized by slow evolution, such as amyotrophic lateral sclerosis and Alzheimer's disease.

 The typical histological characteristic consists of cellular loss, which often selectively affects groups of functionally related neurons, and in a reactive gliosis.
In the early stages, cell loss is observed with difficulty and often the best indicators of neuronal damage are represented by associated glial alterations. For many of these diseases, there is evidence that cell loss occurs due to apoptotic death.

Axonal reaction: it is an alteration that is observed in the cell body during the axon regeneration; it is more evident in the neurons of the anterior horns of the spinal cord when the motor axons are severed or seriously damaged.

 There is an increase in the protein synthesis associated with axonal budding. The morphological variations observed in the pericaral include the enlargement and rounding of the cell body, the peripheral localization of the nucleus, the enlargement of the nucleolus and the dispersion of the Nissl substance from the center towards the cell periphery (central chromatolysis).

Neuronal damage can be associated with a wide spectrum of subcellular changes in neuronal organelles and in the cytoskeleton. Neuronal inclusions may represent a manifestation of aging, when there are intracytoplasmic accumulations of complex lipids (lipofuscin), proteins or carbohydrates.
An abnormal cytoplasmic deposition of complex lipids and other substances also occurs in genetically determined metabolism disorders, in which substrates or their intermediate products accumulate. Viral infections can lead to abnormal intranuclear inclusions, as seen in herpetic infections (Cowdry bodies), to cytoplasmic inclusions, as observed in rabies (Negri bodies) or both, as in cytomegalovirus infections.

Degenerative diseases, gliosis

Some degenerative CNS diseases are associated with neuronal intracytopiasmatic inclusions, such as neurofibrillary clusters of Alzheimer's disease and Lewy bodies of Parkinson's disease; others cause abnormal vacuolization of the pericar and neuronal cellular processes (Creutzfeldt-Jakob disease).


Gliosis, regardless of etiology, is the most important histopathological indicator of CNS damage and is characterized by both hypertrophy and astrocyte hyperplasia. The astrocyte takes its name from its star-like appearance.
These cells possess branched and multipolar cytoplasmic processes, which protrude from the cell body and contain glial fibrillary acidic protein (GFAP), a cellular-specific intermediate filament.
Astrocytes act within the brain as metabolic buffers and as detoxifiers. In addition, through pedunculated processes, which surround the capillaries or extend to the subpocal and subependymal regions, they contribute to the barrier functions and control the flow of macromolecules between the blood, cerebrospinal fluid LCR) and the brain.
In gliosis, the nuclei of the astrocytes, which are typically round or oval (10 micron wide), with a uniformly distributed pale chromatin, enlarge, become vesicles and develop prominent nucleoli. The previously poor cytoplasm expands to take on the appearance of a bright, somewhat irregular pink band around an eccentric nucleus, from which numerous squat and branched processes emerge (gemistocytic astrocytes).

Acute cellular damage, as seen in hypoxia, hypoglycaemia and toxic damage, manifests itself in cell edema, as in other cells. A type II astrocyte of Alzheimer's (which is not related to Alzheimer's disease, but was first described by the same physician) is a cell of the gray substance with a large nucleus 2-3 times normal, a central chromatin pale, an intranuclear glycogen droplet and a prominent nuclear membrane and nucleolus.

 This type of anomaly is observed especially in individuals with long-term hyperammonaemia due to chronic liver disease, Wilson's disease or hereditary metabolic disorders of the urea cycle.
Other types of cell damage lead to the formation of cytoplasmic inclusions.
Rosenthal fibers are rather irregular, thick, elongated and intensely eosinophilic structures that are located in astrocytic processes; they contain two heat-shock proteins (alphaB-crystalline and hsp27) and ubiquitin. Rosenthal fibers are typically present in the areas of long-standing gliosis; they are also characteristic of a glial tumor, the pilocytic astrocytoma.
In Alexander's disease, a leukodystrophy associated with mutations in the gene that codes for GFAP, Rosenthal fibers are found in large quantities in the periventricular, perivascular and subpial sites.
More often observable are the starchy bodies, or polyglucosan bodies. These are concentric, spherical, weakly basophilous, PAS-positive, lamellar structures, with a diameter between 5 and 50 microns, located wherever astrocytic terminal processes exist, especially in the sub-areas and perivascular areas. They consist mainly of glycosaminoglycan polymers, H5P proteins and ubiquitin.
It is believed that they represent a degenerative alteration of astrocytes and increase in number as we age. Lafora bodies, which are observed in the cytoplasm of neurons (as well as hepatocytes, myocytes and other cells) in individuals with myoclonic epilepsy (myoclonic epilepsy at Lafora bodies), are characterized by a similar biochemical and structural composition.

Microglia reactions to damage

Microglia is made up of phagocytic cells derived from the mesoderm which act as resident macrophages of the CNS. They share many surface markers with peripheral monocytes / macrophages (for example, CR3 and CD68). Respond to the damage with: (1) proliferation; (2) development of elongated nuclei (rod cells), as in neurosyphilis; (3) formation of aggregates around small areas of tissue necrosis (microglial nodules); or (4) grouping around the cell bodies of necrotic neurons (neuronophagia).

In addition to resident microglia, blood-derived macrophages may also be present in inflammatory sites.
Reactions of other glial cells to damage


Oligodendrocytes are cells that encompass their cytoplasmic processes around the axons to form myelin. Each oligonedendrocyte myelinates several internodes on multiple axons, as opposed to Schwann cells that mielize peripheral nerves with a one-to-one correspondence between cells and internodes. The damage or apoptosis of oligodendroglial cells is a characteristic of acquired demyelinating disorders and leukodystrophies.

In progressive multifocal leukoencephalopathy, oligodendroglial nuclei may contain viral inclusions. Glial cytoplasmic inclusions, mainly composed of a-sinuclein, are found in oligodendrocytes in multiple systemic atrophy (MSA).
Ependymal cells, ciliated cylindrical epithelial cells that line the ventricles, do not have specific reaction patterns.

 When inflammation or marked dilatation of the ventricular system occurs, the disruption of the ependymal lining is combined with the proliferation of subependymal astrocytes to produce small irregularities on the ventricular surfaces (ependymal granulations).

Some infectious agents, especially CMV, can determine extensive ependymal damage associated with the presence of viral inclusions in ependymal cells. In any case, neither oligodendrocytes nor ependymal cells provide significant responses to most forms of CNS damage.

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