J Pathol Transl Med.  2017 May;51(3):292-305. 10.4132/jptm.2017.02.17.

An Experimental Infarct Targeting the Internal Capsule: Histopathological and Ultrastructural Changes

• Han CW
• Lee KH
• Noh MG
• Kim JM
• Kim HS
• Kim HS
• Kim RG
• Cho J
• Kim HI
• Lee MC

• KMID: 2392596
• DOI: http://doi.org/10.4132/jptm.2017.02.17

Abstract

BACKGROUND
Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes.
METHODS
Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury.
RESULTS
Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume.
CONCLUSIONS
Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.

Keyword

Stroke; White matter; Models, animal; Pathology; Ultrastructure

MeSH Terms

Astrocytes
Axons
Coloring Agents
Extremities
Glial Fibrillary Acidic Protein
Gliosis
Gray Matter
Internal Capsule*
Ischemia
Microscopy
Models, Animal
Models, Theoretical
Myelin Sheath
Necrosis
Neurons
Oligodendroglia
Organelles
Pathology
Plastics
Prevalence
Recovery of Function
Rupture
Stroke
White Matter
Coloring Agents
Glial Fibrillary Acidic Protein
Plastics

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