JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2023

N-M25 (NP)

 

SIGNALMENT (#01-485-2): Sprague-Dawley rat

 

HISTORY: The rat was subjected to an experimental procedure 48 hours prior to euthanasia.

 

HISTOPATHOLOGIC DESCRIPTION: Cerebrum, level of the lateral ventricle and lateral olfactory tract: Unilaterally affecting 85% of the gray matter of the cerebral cortex, corpus callosum, and corpus striatum is a focally extensive to segmental loss of normal neuropil architecture with replacement by pale, loosely arranged, fragmented neuropil and fragmented white matter tracts with increased clear space (liquefactive necrosis).  Multifocally, neurons within the affected focus are shrunken and hypereosinophilic with loss of Nissl substance and nuclear pyknosis or karyolysis (necrosis), there are numerous swollen astrocytes that contain a moderate amount of eosinophilic cytoplasm (gemistocytes), and there is an increase in microglia (gliosis). The corpus callosum and corpus striatum are characterized by spongiosis and increased gitter cells fewer neutrophils, and the corpus striatum is also characterized by moderate capillary proliferation lined by plump endothelial cells (reactive). In the ventral meninges and focally extending into the underlying neuropil, there is mild perivascular cuffing composed of several lymphocytes, plasma cells, few gitter cells, and hemorrhage, fibrin, and edema.  

 

MORPHOLOGIC DIAGNOSIS: Cerebrum, cerebral cortex, corpus callosum, and corpus striatum: Necrosis, liquefactive, unilateral, focally extensive, with gliosis, gitter cells, astrocytosis, and mild lymphoplasmacytic meningitis, Sprague-Dawley rat, rodent.   

 

CAUSE: Experimental 2-hour unilateral occlusion of the middle cerebral artery

 

CONDITION: Cerebral infarction

 

CONDITION SYNONYMS: Stroke

 

GENERAL DISCUSSION:  

• Cerebral infarction is a sudden, focal, intracranial obstruction of vascular supply that results in cerebral necrosis and clinical signs of nervous system dysfunction  
• The outcome is dependent on duration, rate, and severity of ischemia; type and size of vessel involved; and tissue vulnerability to anoxia
• Obstructive lesions of cerebrospinal vessels are not commonly observed in animal; ischemic changes may be absent even when vessels are profoundly altered
• Neurons (especially cerebral cortical and hippocampal neurons and Purkinje cells) and oligodendroglia are the most sensitive, followed by astrocytes, microglia, and endothelial cells 
• Gray matter is more sensitive than white matter
• Deeper laminae of the cerebral cortex are more sensitive than superficial, resulting in laminar cortical necrosis
• Typically arterial; venous infarcts are associated with more extensive hemorrhage

 

PATHOGENESIS:  

• The rate at which ischemia occurs in the CNS determines the degree of injury that follows
  1. With sudden obstruction, e.g, an embolus or Hansen type I disk herniation, many neurons die within minutes and other components within hours
  2. With gradual reduction in blood flow, e.g., atherosclerosis, anastomotic vessels dilate and compensate
• Neurons in the core of the infarcted area die quickly; however, neurons at margin receive some blood from unobstructed vessels
• Axons of degenerating neurons in center release high amounts of glutamate (neurotransmitter) à binding causes increased intracellular calcium in peripheral neurons > cell death and enlargement of area of injury
• If infarction is accompanied by hemorrhage, the hemorrhage displaces the brain tissue, resulting in pressure necrosis and more damage

 

TYPICAL CLINICAL FINDINGS:  

 

TYPICAL GROSS FINDINGS:  

• Areas of cerebral infarction differ in gross appearance from infarcts in other tissues due to high lipid content in the CNS, as well as the relative lack of fibrous connective tissue stroma, resulting in the affected areas becoming soft from liquefactive necrosis
  1. Liquefactive necrosis can often result resulting in cavitation
• In white matter, necrotic areas are often pale; in gray matter, necrotic areas are often hemorrhagic
  1. Likely due to fewer vascular anastomoses in the white matter, resulting in reduced density of the capillary meshwork
• Variable: Acutely, may be undetectable (typically takes 8-24 hours to detect unless there is hemorrhage)
• Subacute: Cerebral edema, dusky gray discoloration, obscure interface between gray and white matter, and mild encephalomalacia
• Chronic: Decreased edema, cavitation of the infarcted area, and brain atrophy

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• 2 hours: Infarct pallor (white matter)
• 3-5 hours: Most neurons ischemic (shrunken and hypereosinophilic with pyknosis, karyolysis, and cell dissolution) and swollen oligodendroglia and astrocytes
• 6-24 hours: Neutrophils infiltrate
• 24-36 hours: Neutrophils peak in number, oligodendroglia decrease, visible astrocyte cytoplasm, astrocyte process degeneration and fragmentation (clasmatodendrosis), and swollen axons and myelin sheaths
• 2 days: Gitter cells appear and neutrophils decrease
• 3-5 days: Gitter cells and capillaries increase and astrocytosis at the margins
• 8-10 days: Liquefactive necrosis, numerous gitter cells, beginning fibroblastic activity and collagen formation (especially adjacent to meninges), and increased astroglial fiber production
• 3 weeks-6 months: Cystic stage, mononuclear cells decrease, astroglial fiber density increases (especially at margins), and astrocyte numbers return to normal

(Adapted from Table 14.1, Miller)

 

DIFFERENTIAL DIAGNOSIS:  

• Hypoxia: Reduced inspired air oxygen 
• Hypotension and cardiac arrest: Suddenly reduced cardiac output
• Toxins: Carbon monoxide, cyanide
• Hypoglycemia: neuroexcitation
• Bilaterally symmetrical necrotizing encephalopathy: idiopathic

 

COMPARATIVE PATHOLOGY:  

• Generally, infarcts in domestic animals are uncommon except in certain circumstances
• Dog: Fibrocartilaginous infarcts in the spinal cord (N-M03), also occurs in the pig, turkey, cat, horse, and mink; rarely, aberrant migration of Dirofilaria immitis to cerebral vasculature or atherogenic vascular degeneration secondary to hypothyroidism can result in cerebral infarction
• Cat: Feline ischemic encephalopathy (N-M23): A cerebral infarction syndrome in mature cats, linked to Cuterebra larvae
• Lab animal:
  1. Gerbils highly susceptible to cerebral infarction following unilateral carotid ligation
• ZEW:
  1. Pinnipeds: Reported occasionally in aged pinnipeds; may be related to age-associated arteriosclerosis

 

References:  

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016: 199.
2. Cantile C, Youssef S. Nervous system.  In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2015:297-300.
3. Colegrove KM, Burek-Huntington KA, Roe W, Siebert U. Pinnipediae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:573. 
4. Miller AD, Porter BF. Nervous System. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier Mosby; 2022: 910-911.

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