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

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

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

Alzheimer disease : dystrophic neurites اسم ورقم المقرر – Course Name and No. 6/25/2019

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

Red Neurons اسم ورقم المقرر – Course Name and No. 6/25/2019

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

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

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

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

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

Gliosis, neuronal loss in this picture اسم ورقم المقرر – Course Name and No. 6/25/2019

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 اسم ورقم المقرر – Course Name and No. 6/25/2019

CENTRAL NERVOUS SYSTEM TRAUMA اسم ورقم المقرر – Course Name and No. 6/25/2019

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

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

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

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 اسم ورقم المقرر – Course Name and No. 6/25/2019

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 اسم ورقم المقرر – Course Name and No. 6/25/2019

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

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

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

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

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

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 اسم ورقم المقرر – Course Name and No. 6/25/2019

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

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

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