1. Cellular injury of the nervous system
Dr. Mamlook Elmagraby
اسم ورقم المقرر – Course Name and No.
6/25/2019

2. Objectives of the lecture:-
At the end of this lecture the students should:
Understand the role of the different constituents of CNS cells in the disease status
Compare the “trauma” and “injury” concepts
Explain the basic pathological descriptive terms used in CNS cellular injury and trauma
Correlate the different patterns of cellular injury with some important clinical examples
Analyze the clinical entities that result from CNS trauma
اسم ورقم المقرر – Course Name and No.
6/25/2019

3. Features of Neuronal Injury:
Acute injury
Axonal reaction
Formation of neuronal inclusions
Aggregation of abnormal proteins
Neuronophagia
Neuronal processes may become thickened and tortuous (dystrophic neurites) in some diseases
اسم ورقم المقرر – Course Name and No.
6/25/2019

4. Alzheimer disease : dystrophic neurites
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6/25/2019

5. Acute neuronal injury
This is most commonly caused by hypoxia/ischemia but also under the influence of toxic or infectious agents that can kill neurons
Affected neurons show  
shrinkage of the cell body
pyknosis of the nucleus
disappearance of the nucleolus
loss of Nissl substance
intense eosinophilia of the cytoplasm (“red neurons”)
Injured axons undergo swelling and show disruption of axonal transport and variable degrees of cerebral edema
اسم ورقم المقرر – Course Name and No.
6/25/2019

6. Red Neurons
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6/25/2019

7. Axonal reaction:
It occurs following transection or other severe injury of the axon
It is characterized by histologic and ultrastructural changes in the cytoplasms of the neuron (perikaryon)
Following axonal injury, the perikaryon swells
The ribosomes of rough endoplasmic reticulum (Nissl substance) are lost (chromatolysis)
اسم ورقم المقرر – Course Name and No.
6/25/2019

8. Compare this neuron with the two normal neurons (red arrows).
Note the swollen nerve cell body with homogeneous pink cytoplasm due to loss of Nissl substance (black arrow). The nucleus is displaced to the left. This is an example of central chromatolysis in a spinal cord neuron.
Compare this neuron with the two normal neurons (red arrows). 
اسم ورقم المقرر – Course Name and No.
6/25/2019

9. Formation of neuronal inclusions:
Neuronal inclusions can be intracytoplasmic or intranuclear
Typical examples include:
lipofuscin
viral inclusions
nuclear inclusions such as those seen in herpes encephalitis
nuclear and cytoplasmic inclusions (cytomegalovirus infection)
اسم ورقم المقرر – Course Name and No.
6/25/2019

10. Aggregation of abnormal proteins:
Cytoplasmic bodies are found in neurons in several neurodegenerative diseases:
The formation of neurofibrillary tangles in Alzheimer disease
The formation of cytoplasmic Lewy bodies made out of a-synuclein in Parkinson disease
اسم ورقم المقرر – Course Name and No.
6/25/2019

11. Astrocytes in Injury and Repair:
Astrocytes are the principal cells responsible for repair and scar formation in the brain (gliosis) 
In response to injury, astrocytes undergo both hypertrophy and hyperplasia
Gemistocytic astrocyte: The scant cytoplasm expands and takes on a bright pink hue, and the cell extends multiple stout, ramifying processes
Rosenthal fibers:  thick, elongated, brightly eosinophilic protein aggregates found in astrocytic processes
اسم ورقم المقرر – Course Name and No.
6/25/2019

12. Gliosis, neuronal loss in this picture
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6/25/2019

13. Reactions of Microglia to Injury:
In other settings (infections) they develop elongated nuclei (rod cells)
Reactions of Microglia to Injury:
When activated by tissue injury, they proliferate and become more prominent Microglial cells take on the appearance of activated macrophages in areas of demyelination, organizing infarct, or hemorrhage In other settings (infections) they develop elongated nuclei (rod cells) Microglial nodules: Aggregates of elongated microglial cells at sites of tissue injury Neuronophagia: Similar collections can be found collecting around and phagocytosing injured neurons
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6/25/2019

14. CENTRAL NERVOUS SYSTEM TRAUMA
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6/25/2019

15. Trauma to the brain and spinal cord is a significant cause of death and disability The severity and site of injury affect the outcome A blow to the head may be penetrating or blunt The extent and distribution of resulting traumatic brain lesions depend on several factors
اسم ورقم المقرر – Course Name and No.
6/25/2019

16. External signs of head injury may not indicate the severity of brain damage resulting from trauma When the brain is damaged, the injuries may involve the parenchyma, the vasculature, or both
اسم ورقم المقرر – Course Name and No.
6/25/2019

17. Traumatic Parenchymal Injuries
The main forms of spinal cord or brain injury caused by physical forces:
Concussion:
Reversible altered consciousness from head injury in the absence of contusion
The characteristic transient neurologic dysfunction includes
loss of consciousness,
temporary respiratory arrest, and
loss of reflexes
Neurologic recovery is complete
اسم ورقم المقرر – Course Name and No.
6/25/2019

18. Contusions (bruising):
A contusion is caused by rapid tissue displacement, disruption of vascular channels and subsequent hemorrhage, tissue injury, edema
It involves a coup lesion at the site of the impact of force or a contrecoup contusion, opposite to it
Contusions are common in regions of the brain overlying rough and irregular inner skull surfaces
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6/25/2019

19. Neutrophils preceding the appearance of macrophages
Contusions are wedge-shaped, with the widest aspect closest to the point of impact
Morphologic evidence of injury in the neuronal cell body (nuclear pyknosis, cytoplasmic eosinophilia, cellular disintegration) takes about 24 hours to appear
Neutrophils preceding the appearance of macrophages
Trauma affects the superficial layers most severely
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6/25/2019

20. In sites of old contusions
There are depressed, retracted, yellowish brown patches
More extensive hemorrhagic regions of brain trauma give rise to larger cavitary lesions
Gliosis and residual hemosiderin laden macrophages predominate
اسم ورقم المقرر – Course Name and No.
6/25/2019

21. Diffuse axonal injury
It is subtle but widespread injury to axons within the brain sometimes with serious consequences
The movement of one region of brain relative to another is thought to disrupt axonal integrity and function
50% of patients who develop coma shortly after trauma are believed to have diffuse axonal injury
These lesions are asymmetric and are commonly found near the lateral ventricles and in the brain stem
These lesions take the form of axonal swellings
اسم ورقم المقرر – Course Name and No.
6/25/2019

22. Traumatic Parenchymal Injuries
Lacerations (tearing of tissue):
It is a severe form of brain injury
It is typically seen in vehicular accidents
It is associated with bleeding and high mortality
Penetration of the brain by a projectile body (bullet or a skull fragment from a fracture) causes a laceration, with tissue tearing, vascular disruption, hemorrhage
اسم ورقم المقرر – Course Name and No.
6/25/2019

23. Traumatic Vascular Injury
CNS trauma often directly disrupts vessel walls, leading to hemorrhage
Depending on the affected vessel, the hemorrhage may be
epidural
subdural
subarachnoid
Intraparenchymal
Subarachnoid and intraparenchymal hemorrhages most often occur at sites of contusions and lacerations
اسم ورقم المقرر – Course Name and No.
6/25/2019

24. Traumatic Vascular Injury
Epidural Hematoma
Epidural hemorrhage results from bone fractures at the base of the skull that tear the middle meningeal artery
Arterial bleeding leads to the formation of a hematoma in the space between the inner aspect of the cranial bones and the dura mater
Hematoma that forms under arterial pressure grows progressively, and without proper surgical intervention, it is fatal within several hours after injury
Clinically, patients can be lucid for several hours between the moment of trauma and the development of neurologic signs
اسم ورقم المقرر – Course Name and No.
6/25/2019

25. Head, acute epidural hemorrhage – Gross, autopsy presentation
After removal of the skull cap at autopsy, fresh blood overlying the dura mater in the right frontal area is seen.
Because epidural hemorrhages are almost invariably arterial in origin, they tend to accumulate very quickly, causing a rapid increase in intracranial pressure and loss of consciousness
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6/25/2019

26. Traumatic Vascular Injury
Subdural Hematoma
Rapid movement of the brain during trauma can tear the bridging veins that extend from the cerebral hemispheres through the subarachnoid and subdural space to the dural sinuses
The disruption of these veins wall produces bleeding into the subdural space
Infants and elderly persons are susceptible to subdural hematomas
اسم ورقم المقرر – Course Name and No.
6/25/2019

27. Subdural hematomas typically become manifest within the first 48 hours after injury They are most common over the lateral aspects of the cerebral hemispheres and may be bilateral Neurologic signs are attributable to the pressure exerted on the adjacent brain Symptoms may be localizing or nonlocalizing This venous bleeding may stop on its own
اسم ورقم المقرر – Course Name and No.
6/25/2019

28. Brain, acute subdural hematoma - Gross, autopsy presentation
acute subdural hematoma, visible here through the dura mater as an area of purple discoloration overlying the left cerebral hemisphere.
اسم ورقم المقرر – Course Name and No.
6/25/2019