Neuropathology: Neuronal Damage and Gliosis
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Questions and Answers

In the context of neuronal damage, which of the following mechanisms is least likely to directly result in the formation of neuronal inclusions?

  • Cytoplasmic deposition of substances due to inherited metabolic disorders.
  • Accumulation of complex lipids as a manifestation of aging.
  • Intranuclear inclusions resulting from viral infections affecting the nervous system.
  • Acute failure of ATP-dependent ion channels due to hypoxic injury. (correct)
  • Which of the following characteristics distinguishes Alzheimer type II astrocytes from gemistocytic astrocytes?

  • Occurrence in response to acute hypoxic injury.
  • Presence of abundant eosinophilic cytoplasm.
  • Association with long-standing hyperammonemia. (correct)
  • Formation of Rosenthal fibers within astrocytic processes.
  • What is the primary protein component found within Rosenthal fibers, structures typically observed in long-standing gliosis?

  • Tau protein
  • Glial fibrillary acidic protein (GFAP) (correct)
  • Alpha-synuclein
  • Amyloid precursor protein (APP)
  • Which of the following best describes the sequential order of events in astrogliosis following a significant traumatic brain injury?

    <p>Cytoplasmic swelling as an initial response, followed by the simultaneous processes of hypertrophy and hyperplasia. (D)</p> Signup and view all the answers

    What distinguishes the distribution of corpora amylacea from that of Rosenthal fibers within the central nervous system?

    <p>Corpora amylacea are characteristically located in subpial and perivascular zones, while Rosenthal fibers are found within astrocytic processes in long-standing gliosis. (B)</p> Signup and view all the answers

    In cases of chronic hepatic encephalopathy, which specific type of astrocyte is most likely to be observed?

    <p>Alzheimer type II astrocyte (C)</p> Signup and view all the answers

    Which of the following viral infections is characterized by cytoplasmic inclusions in neurons?

    <p>Rabies (D)</p> Signup and view all the answers

    The presence of corpora amylacea in the CNS is most indicative of what pathological process?

    <p>Progressive astrocytic degeneration (A)</p> Signup and view all the answers

    How does the distribution of Nissl substance differ between the perikaryon and the axon of a neuron?

    <p>Nissl substance extends into dendrites, but it’s absent in the axon. (D)</p> Signup and view all the answers

    Which characteristic is most useful for distinguishing oligodendrocytes from astrocytes in histopathological samples of the central nervous system?

    <p>The quantity of perinuclear cytoplasm; oligodendrocytes have minimal cytoplasm, while astrocytes have more. (C)</p> Signup and view all the answers

    What is the functional implication of the unique morphology of ependymal cells within the central nervous system?

    <p>Their cuboidal shape and ciliated surface are ideally suited for lining ventricular cavities and facilitating CSF movement. (D)</p> Signup and view all the answers

    Which of the following statements regarding neuronal structure and function is most accurate?

    <p>Neurons are specialized cells with electrically excitable membranes designed for the reception, integration, and communication of information, varying in shape from stellate to pyramidal. (D)</p> Signup and view all the answers

    How does the function of macroglia and microglia compare in response to CNS injury?

    <p>Macroglia, including astrocytes and oligodendrocytes, modulate the tissue environment, while microglia act as phagocytes to remove debris. (D)</p> Signup and view all the answers

    Which of the following is the primary distinction between the roles of Schwann cells and oligodendrocytes in the nervous system?

    <p>Schwann cells myelinate a single axon segment in the peripheral nervous system; oligodendrocytes can myelinate multiple segments of several axons in the central nervous system. (D)</p> Signup and view all the answers

    Consider a scenario where a histopathological analysis reveals a significant decrease in the amount of neuropil within the gray matter of the cerebral cortex. What implications would this have for neuronal function?

    <p>Reduced neuropil indicates a decrease in dendritic and axonal processes, potentially impairing neuronal communication and integration. (C)</p> Signup and view all the answers

    How would a lesion impacting the axon hillock of a neuron most directly affect its function?

    <p>Inhibition of action potential initiation, preventing the neuron from transmitting signals. (C)</p> Signup and view all the answers

    In the context of acute neuronal injury, which sequence accurately reflects the morphological changes observed in 'red neurons' following an irreversible hypoxic/ischemic insult?

    <p>Shrinkage of the cell body, pyknosis of the nucleus, disappearance of the nucleolus, loss of Nissl substance, and intense eosinophilia of the cytoplasm. (A)</p> Signup and view all the answers

    How does subacute and chronic neuronal injury, as seen in diseases like amyotrophic lateral sclerosis (ALS), manifest differently from acute neuronal injury in terms of histological presentation?

    <p>Subacute and chronic injury typically involves selective cell loss within functionally related neuronal groups accompanied by significant reactive gliosis, whereas acute injury shows more uniform and immediate cell death ('red neurons'). (A)</p> Signup and view all the answers

    Which cellular process underlies the axonal reaction observed in damaged neurons, and how does this reaction contribute to the morphological changes seen in the cell body?

    <p>Increased protein synthesis, which supports axonal sprouting and is reflected in enlargement of the cell body, peripheral displacement of the nucleus, and central chromatolysis. (A)</p> Signup and view all the answers

    A researcher is examining a tissue sample from a patient with a suspected motor neuron disease. Under microscopic examination, the anterior horn cells of the spinal cord exhibit enlargement of the cell body, peripheral displacement of the nucleus, and dispersion of Nissl substance from the center to the periphery of the cell. Which of the following processes is most likely occurring in these neurons?

    <p>Axonal Reaction (D)</p> Signup and view all the answers

    Following a traumatic brain injury, a patient's MRI reveals areas of acute CNS hypoxia/ischemia. If a biopsy were taken from the affected area 24 hours post-injury, which set of histological findings would most strongly suggest acute neuronal injury?

    <p>Shrunken cell bodies with pyknotic nuclei, loss of nucleoli, loss of Nissl substance, and intense eosinophilia of the cytoplasm. (D)</p> Signup and view all the answers

    In distinguishing between the cellular responses to acute versus chronic neurodegenerative conditions, which statement accurately contrasts the roles of neuronal and glial reactions?

    <p>Acute injuries induce rapid neuronal necrosis followed by a glial response to clear debris, whereas chronic conditions feature selective neuronal loss accompanied by progressive gliosis. (B)</p> Signup and view all the answers

    A researcher is investigating potential therapeutic interventions for spinal cord injuries. One approach aims to enhance axonal regeneration following injury. Which of the following cellular changes would be the most relevant indicator of successful axonal regeneration in treated neurons?

    <p>Enlargement of the neuronal cell body, peripheral displacement of the nucleus, and dispersion of Nissl substance. (A)</p> Signup and view all the answers

    In the context of CNS injury and repair, how do the inherent characteristics of neurons, specifically their limited capacity for cell division, influence the long-term outcomes of neurological damage?

    <p>The post-mitotic nature of neurons ensures that any neuronal loss leads to permanent neurological deficits, unless stem cell-based therapies are employed. (B)</p> Signup and view all the answers

    Flashcards

    CNS Components

    The parts that make up the central nervous system: brain, spinal cord, olfactory tract, optic nerve, and retina.

    Gray Matter

    Brain regions containing large numbers of nerve cell bodies; it has a distinct color and includes neuropil with axons and dendrites.

    White Matter

    Regions composed mainly of myelinated fibers in the CNS, giving them a lighter appearance.

    Neuron Structure

    A specialized, electrically-excitable cell for communication; can have various shapes like stellate or pyramidal.

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    Nissl Substance

    Basophilic granules in the nerve cell body, important for protein synthesis, found in cytoplasm and dendrites.

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    Axon

    The long, slender projection of a neuron that transmits impulses away from the cell body; is ensheathed by supportive cells.

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    Astrocyte

    A star-shaped neuroglial cell with various processes that supports and maintains neuronal function.

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    Microglia

    The small glial cells that act as the immune response in the CNS, characterized by elongated, hyperchromatic nuclei.

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    Neuronal reaction to injury

    Response of neurons to injury includes necrosis and apoptosis, leading to neurological deficits.

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    Acute neuronal injury

    A rapid reaction in the CNS following hypoxia or ischemia, often resulting in 'red neurons'.

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    'Red neurons'

    Morphological changes in neurons post-injury, visible around 12 to 24 hours later.

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    Subacute and chronic neuronal injury

    Gradual neuronal death due to prolonged disease processes, like ALS, with cell loss and gliosis.

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    Axonal reaction

    Neuronal body reactions to aids axonal regeneration, seen in damaged motor axons.

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    Characteristic features of acute injury

    Includes shrinkage of cell body, pyknosis, nucleolus loss, and eosinophilia.

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    Reactive gliosis

    Proliferation of glial cells in response to neuronal injury, often precedes recognizable cell loss.

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    Subcellular alterations

    Changes in neuron organelles and cytoskeleton associated with damage.

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    Neuronal inclusions

    Accumulations of lipids, proteins, or carbohydrates in neurons, often due to aging.

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    Cowdry body

    Abnormal intranuclear inclusions seen in herpetic infections.

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    Negri body

    Cytoplasmic inclusions associated with rabies infection.

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    Gliosis

    Proliferation of astrocytes in response to CNS injury, indicating damage.

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    Gemistocytic astrocytes

    Large, reactive astrocytes with a distinctive pink appearance seen in injury.

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    Rosenthal fibers

    Thick, eosinophilic structures found in astrocytic processes during gliosis.

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    Corpora amylacea

    Faintly basophilic, round structures accumulated in astrocytic processes with age.

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    Study Notes

    Basic Histopathologic Neuronal Reaction to Injury

    • Histopathology studies microscopic changes in tissues to understand injury responses.
    • The central nervous system (CNS) comprises the brain, spinal cord, olfactory tract and bulb, optic nerve and retina.
    • Gray matter: Contains nerve cell bodies, neuropil (dendrites and axon terminals), and forms a network around neuronal cell bodies.
    • White matter: Composed mainly of myelinated fibers, identified by its color.

    Components of CNS

    • The CNS includes the brain, spinal cord, olfactory tract, bulb, and optic nerve and retina.
    • Gray matter consists of nerve cell bodies, dendrites, and axon terminals, giving it a gray color.
    • White matter is composed of myelinated fibers that give it a white appearance.

    Light Micrograph of Cerebral Cortex

    • The micrograph displays pia mater and cortical gray matter with neuronal somas surrounded by neuropil.
    • Neuropil consists of intertwined axons, dendrites, and glial cells.

    Nerve Cell (Neuron)

    • Specialized, long-lived cells that don't replicate.
    • Multibranched with electrically-excitable membranes.
    • Responsible for receiving, integrating, and communicating information.
    • Vary in shape (stellate to pyramidal), size (4-125 µm).
    • Perikaryon (cell body/soma) is also sometimes called a neuron.
    • Nucleus contains a prominent nucleolus.

    Nissl Substance

    • Basophilic granules in the nerve cell perikaryon.
    • Fills the cytoplasm of nerve cells and extends into dendrites.
    • Composed of concentrated collections of ribosomes and endoplasmic reticulum.

    Neuron Axon

    • Slender, cylindrical structure arising from the axon hillock of the perikaryon.
    • Only one axon per neuron.
    • Ensheathed by supporting Schwann cells (peripheral nervous system) or oligodendrocytes (central nervous system).
    • Myelin sheaths may be present (myelinated axons) or absent (unmyelinated axons).

    Neuroglia

    • Supporting cells in the CNS, not nerve cells.
    • Includes:
      • Macroglia: Astrocytes, oligodendrocytes, and ependymal cells.
      • Microglia.

    Astrocytes

    • Star-shaped cells with branched processes.
    • Oval nucleus with little perinuclear cytoplasm.
    • Many cell processes, important for nutrient supply.

    Oligodendrocytes

    • Small, darkly staining cells with a round nucleus, minimal cytoplasm, and few processes, no cytoplasmic filaments.
    • Produce myelin sheaths in the CNS.

    Ependymal Cells

    • Ciliated cuboidal epithelial cells lining ventricular cavities of the CNS.
    • Form the lining of the ventricular cavities.

    Microglia

    • Small, elongated cells with thin, rod-shaped, hyperchromatic nuclei.
    • Reactive state easily distinguished by rod cells.
    • Respond to injury through proliferation, increased size, and number of microglia (act like macrophage cells).

    Reactions of Cells to Injury: Neuronal and Glial

    • Neuronal reaction to injury includes changes in neuron size/body shape, nucleus, and cytoplasm.
    • Glial reaction to injury includes changes in glial shape, size/body shape, nucleus, and cytoplasm.

    Reactions of Neurons to Injury

    • Neurons don't divide, so cell loss from injury leads to neurological deficits.
    • Stem cells may facilitate repair but aren't sufficient in many cases.

    Principles of Neuronal Injury

    • Categories of neuronal injury: Acute, subacute/chronic, axonal reaction, subcellular alterations, intracytoplasmic inclusion.

    Acute Neuronal Injury

    • Spectrum of changes in the CNS due to hypoxia/ischemia or other insults.
    • Cell death is the defining hallmark.
    • Characterized by "red neurons" visible in histological preparations 12-24 hours after irreversible hypoxic/ischemic insults.
    • Morphological features: Shrinkage of the cell body, nuclear pyknosis (small), disappearance of Nissl substance, intense eosinophilia of cytoplasm.

    Sub-Acute and Chronic Neuronal Injury

    • Progressive neuronal death due to disease.
    • Important histologic feature is cell loss, often selectively affecting functionally related groups.
    • Reactive gliosis is a hallmark feature.
    • Early-stage cell loss is difficult to detect, but reactive glial changes help identify the disease process.

    Axonal Reaction

    • Occurs with axonal trauma in neurons.
    • Characterized by increased protein synthesis and axonal sprouting in the neuron.

    Subcellular Alterations

    • Neuronal damage can involve organelles and cytoskeleton.
    • Inclusions of lipids, proteins, or carbohydrates are found in aging neurons and in various genetic disorders.
    • Viral infections may also cause cytoplasmic or intranuclear inclusions (e.g., Cowdry body, Negri body).

    Reactions of Astrocytes to Injury

    • Gliosis (or astrogliosis) is an important marker associated with CNS injury following various etiologies.
    • Gliosis is characterized by astrocyte hypertrophy and hyperplasia at injury sites.

    Injury to Astrocytes

    • Direct injury triggers cytoplasmic swelling (due to ion channel malfunction).
    • Seen in acute insults that disrupt ATP-dependent ion channels (hypoxia, hypoglycemia, and toxic injuries).

    Gemistocytic Astrocytes

    • Large, pink cells with a pale nucleus seen during reactive processes.

    Alzheimer Type II Astrocytes

    • Gray matter cells with a large nucleus, pale chromatin, prominent nuclear membrane, and often a glycogen droplet.
    • Not specific to Alzheimer's disease, instead seen in conditions like chronic liver disease, Wilson disease, and urea cycle disorders.

    Piloid Gliosis-Rosenthal Fibers

    • Thick, elongated, eosinophilic astrocytic processes.
    • Contain proteins and seen in long-standing gliosis around tumors, vascular abnormalities.

    Corpora Amylacea

    • Round, faintly basophilic, concentrically lamellated structures within astrocytic processes, particularly in the subpial and perivascular areas.

    Reactions of Other Glial Cells to Injury

    • Oligodendrocytes and ependyma show limited reactions to CNS injury compared to astrocytes.
    • Oligodendrocytes' main function is to surround axons and form myelin.
    • Injury affecting oligodendrocytes is associated with demyelinating disorders.
    • Ependymal cells may show disruption due to system inflammation or dilation, forming granular processes.

    Reactions of Microglia to Injury

    • Microglia, the CNS's tissue macrophages, respond to injury by proliferating, developing elongated nuclei ("rod cells"), forming aggregates around tissue necrosis ("microglial nodules"), and surrounding degenerating neurons ("neuronophagia").

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    Description

    Test your knowledge of neuropathology with questions on neuronal inclusions, astrocyte types (Alzheimer type II vs. gemistocytic), and astrogliosis. Explore the features of Rosenthal fibers, corpora amylacea, and Nissl substance distribution. Also, viral inclusions in neurons are covered.

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