NEUROPATHOLOGY- BASIC REACTIONS

---

[ CATS Home | About CATS | CATS Teaching Modules | Course Outline | Neuropathology | UVM Department of Pathology | Other Pathology Sites | UVM College of Medicine | UVM ]

---

VOCABULARY
Terms you should be familiar with:

Blood brain barrier
Cerebral spinal fluid
Neuron
Astrocyte
Oligodendroglial cell
Ependymal cell
Microglial cell
Anoxic/ischemic injury
Central chromatolysis
Wallerian degeneration
Astrocyte
Astrocytosis
Reactive astrocytosis
Gliosis
Gitter cell
Hydrocephalus
Cerebral edema
Intracranial pressure
Brain herniation
Respirator brain

OBJECTIVES: The objectives of this hour are to give you an understanding of the special nature of the nervous system in terms of structure and function, to impart a basic terminology for the cellular cast of characters of the central nervous system, to describe the basic reactions that these characters undergo in pathologic conditions, and to relate these basic reactions to what can be seen in the brain with the naked eye.

I. SPECIAL FEATURES

Features of the Central Nervous System

• Complexity of Structure and Function
  
  
• Non-Regenerative Capacity of the Functional Unit- The neuron
  
  
• Glial framework rather than fibroblastic
  
  
• Sequestered immunologically, pharmacologically, and chemically- Concept of the blood brain barrier
  
  
• Housed in a rigid, non-expansible container, i.e. the skull
  
  
• No known lymphoid drainage
  
  
• Cerebral spinal fluid system
  
  
• Exquisite sensitivity to deprivation of oxygen and glucose supply- No capacity for storage of these elements

Back to Top

II. CELLULAR CAST OF CHARACTERS

Cellular features of the central nervous system. In spite of the complexity of structure and function of the central nervous system, there are only a few cells with which to be familiar.

• Neuron: Functional unit of the CNS. The cerebrum has been estimated to contain more than 20 billion neurons, and these communicate by a network of more than 1 trillion synapses.
  
  
  • Neuroectodermal origin
  • Conventional wisdom suggests that we are born with all the neurons we will ever have, however recent evidence suggests that some degree of neuronal regeneration and cell division may be possible. Although classical teaching suggests that normal aging is associated with neuronal loss, more recent studies indicate that large neurons shrink, but the total number of neurons remains constant.
  • Size and shape of neurons varies depending on function, neurotransmitter profile and location in the CNS.
  • In routine histologic sections stained with H and E, the most prominent features of a cortical neuron are clumps of Nissl substance dispersed throughout the cytoplasm, a prominent nucleus (usually containing a single prominent nucleolus) located in the base of the cell, and an apical dendrite whose axis projects perpendicularly and towards the outer surface of the cortical ribbon. Dendritic arborizations and axonal projections are not appreciated in routine sections.
    
    
• Astrocyte: Basic function is to provide structural framework for the CNS and probably provides metabolic support for neurons.
  
  
  • Neuroectodermal origin
  • Two types in normal tissue sections
    • Protoplasmic- gray matter
    • Fibrous or fibrillary- white matter
  • Important point: In routine tissue sections stained with H and E, one cannot appreciate the cytoplasm or cell processes of astrocytes. See below under reactions to injury.
  • The number of astrocytes in the cortical ribbon increases with aging.
  • Astrocytic processes reach out to touch neurons, capillary walls, pial surfaces, and other astrocytes.
    
    
• Oligodendroglial Cell
  
  
  • Similar in appearance to astrocytes, but nucleus is smaller and darker.
  • Neuroectodermal origin.
  • Produces and maintains myelin of the CNS. Unlike the Schwann cell of the peripheral nervous system, that is capable of contributing myelin for only one internodal length of one axon, the oligodendroglial cell is capable of contributing myelin to several axons, or to several lengths of one axon.
  • Like the astrocyte, oligodendroglial cells do not manifest their cytoplasm or cell processes in routine tissue sections.
  • Most prominently seen in white matter.
    
    
• Ependymal Cell
  
  
  • Neuroectodermal origin
  • Line the ventricular compartments of the brain
  • Have the appearance of cuboidal epithelium, with cilia that project into the CSF of the ventricles
    
    
• Microglial Cell: Its origin and existence in the CNS are controversial.
  
  
  • Mesodermal origin. Recent immunocytochemical data suggests that the microglial cell is derived from the bone marrow, and migrates to the CNS.
  • In its "resting" state, the microglial cell is rarely seen in routine tissue sections, but when present appears as a small, elongated, dark nucleus.
  • Has no known function in the normal state.
    
    
• Capillary Endothelial Cells: Have the appearance of endothelial cells elsewhere in the body. Important point: the blood brain barrier resides at the inner tight junction between endothelial cells.

Back to Top

III. REACTIONS TO INJURY

• Neuron
  
  
  • Anoxic/Ischemic Injury: If the neuron is deprived of oxygen or glucose for more than 5 to 7 minutes, it dies. This is manifest as the cytoplasm becoming pink and homogeneous (eosinophilic) and the nucleus becoming dark and shrunken (pyknotic), with eventually the cell disappearing entirely. The injury must have occurred 6 to 8 hours before death in order for this change to be visible. This is not a reversible reaction. Neurons in cortical layers III and V, Sommer's sector of the hippocampus and Purkinje cell layer of the cerebellum are most susceptible to this type of injury.
  • Central chromatolysis (axonal injury): This is a secondary nerve cell change due to damage or disease of the axon. It is reversible if the integrity of the axon is restored. The neuron appears rounded and swollen, the Nissl substance becomes clumped at the periphery of the cell, and the nucleus also migrates to the periphery.
  • Simple atrophy: Seen in a number of conditions, in particular the neurodegenerative diseases. Basically, the neuron shrivels up and disappears, usually for unknown reasons. Synonymous term is "cell sclerosis".
  • Trans-synaptic degeneration: If the primary input to a neuron is lost, or conversely, the area to which a neuron projects primarily is injured, then the neuron in either case undergoes simple atrophy (e.g., trans-synaptic degeneration will occur in the lateral geniculate nucleus if the eye is enucleated).
  • Wallerian degeneration: Secondary breakdown of the myelin sheath distal to an area of injury to the nerve cell body or its axon (e.g., degeneration of the descending pyramidal system following a cortical infarct).
    
    
• Astrocyte
  
  
  • Initially, after an injury to the CNS, astrocytes undergo proliferation that consists of an increase in the number of astrocytic nuclei associated with swelling of individual nuclei. This process is termed astrocytosis.
  • Starting at 1 week after an injury, the cytoplasm of astrocytes becomes visible and appears pink and glassy. Fine processes are also visible and these represent glial fibers that contribute to the "scar" of the repair process. Eventually, the area of injury (e.g., an infarct) appears as a cystic lesion with a surrounding wall containing glial fibers. Fibroblasts play no role in repair and scar formation in the CNS. The process of laying down glial fibers is known as gliosis. The astrocytes whose cytoplasm is visible are termed reactive astrocytes.
    
    
• Microglial Cell
  
  
  • In the presence of injury in the CNS, usually about 5 days after the insult, microglial cells proliferate. This process is known as microglial activation.
  • Over the next 10 days (days 5 to 15 post injury), the activated microglial cells differentiate into macrophages.
  • These macrophages (known as gitter cells in the CNS) phagocytize debris associated with the injury, following which they migrate out of the CNS into the vascular space.
  • Gitter cells are particularly prominent in diseases associated with acute, marked tissue destruction (e.g., infarcts) and in diseases associated with myelin destruction (e.g., multiple sclerosis). They are generally not seen in tumors or degenerative diseases.

Back to Top

IV. DIFFERENTIAL SENSITIVITY TO ANOXIC/ISCHEMIC INJURY

Sensitivity of cells to injury, from most to least: neurons, axons, myelin, oligodendroglial cells, astrocytes, microglial cells, and capillary endothelial cells. Because of this, in various degrees of injury, some elements are destroyed, while others may be stimulated to proliferative activity.

V. HYDROCEPHALUS

• About 750 ml of CSF are secreted by the choroid plexus of the lateral and fourth ventricles daily.
  
  
• The CSF circulation should be well known to you.
  
  
• An abnormal amount of CSF is called hydrocephalus. This can result from:
  
  
  • CSF over production (e.g., choroid plexus tumors).
  • Obstruction of flow of CSF (termed internal or non-communicating or obstructive hydrocephalus).
  • Failure of absorption of CSF by the arachnoidal granulations (termed external or communicating or non-obstructive hydrocephalus).
  • Compensatory as a result of loss of CNS tissue (termed hydrocephalus ex vacuo).

Back to Top

VI. CEREBRAL EDEMA

Term that describes increased water content or maldistribution of water in CNS parenchyma. The total water content of the brain may or may not be increased depending on the nature of the edema. If the total water content of the brain is increased, the brain will appear swollen to the naked eye. Cerebral edema is a non-specific reaction to injury that occurs in a wide variety of CNS diseases. The two basic types of cerebral edema are:

• Vasogenic: Affects primarily white matter and is due to leaky blood vessels (i.e., a breakdown in the blood brain barrier). Water accumulates in the extracellular space, and total water content of the brain is generally increased. May be responsive to treatment with anti-osmotic agents.
  
  
• Cytotoxic: Affects primarily gray matter and is due to excess water entering the intracellular space. Due to a disturbance of cell membrane function (such as may be seen in anoxic/ischemic injury) and total water content of the brain is generally not increased. Is usually not responsive to anti-osmotic agents.

Back to Top

VII. RAISED INTRACRANIAL PRESSURE AND BRAIN HERNIATION

Keeping in mind that the brain is housed in a rigid, non-expansible container, it is only capable of a limited increase in its volume before it begins to bump up against the inside of the skull. In situations of increased brain volume (e.g., due to cerebral edema or an expanding tumor mass), intracranial pressure will be raised. Normal intracranial pressure is 100 to 200 mm H2O. Since intracranial pressure is reflected in the CSF, it may be measured by a manometer during the performance of a lumbar puncture. When intracranial pressure exceeds a critical threshold, the brain will seek a release through a pathway of least resistance. This release is known as brain herniation, and may be classified using the following terminology:

• Wound or Surgical Herniation: Herniation of brain tissue through a surgical defect in the skull.
  
  
• Subfalcian Herniation: Herniation of the cingulate gyrus under the falx cerebri.
  
  
• Uncal Herniation: Herniation of the uncus through the tentorium cerebelli (usually a terminal event).
  
  
• Tonsillar Herniation: Herniation of the cerebellar tonsils through the foramen magnum (usually a terminal event).

VIII. RESPIRATOR BRAIN

Due to the wonders of modern medicine, it is now possible to maintain cardiac and pulmonary function in patients who have suffered severe, but sublethal, brain injuries. In such situations, the brain may swell due to severe cerebral edema such that the intracranial pressure eventually exceeds mean arterial pressure. When this happens, the brain suffers a severe anoxic/ischemic insult that affects all cellular elements. In a sense, the brain begins to undergo autolysis in vivo while the patient is maintained on a respirator and other life support systems. The term given to this pathologic condition is respirator brain. The brain grossly appears slate gray in color, and microscopically there is no cellular response to the injury since all cellular elements are dead.

Back to Top

Go Back to Course Outline

Go Back to Neuropathology

 

---

[ CATS Home | About CATS | CATS Teaching Modules | UVM Department of Pathology | Other Pathology Sites | UVM College of Medicine | UVM ]

---