Experimental cerebral hypoperfusion induces white matter injury and microglial activation in the rat brain

E. Farkas, Gergely Donka, Rob A I de Vos, A. Mihály, F. Bari, Paul G M Luiten

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Though cerebral white matter injury is a frequently described phenomenon in aging and dementia, the cause of white matter lesions has not been conclusively determined. Since the lesions are often associated with cerebrovascular risk factors, ischemia emerges as a potential condition for the development of white matter injury. In the present study, we induced experimental cerebral hypoperfusion by permanent, bilateral occlusion of the common carotid arteries of rats (n=6). A sham-operated group served as control (n=6). Thirteen weeks after the onset of occlusion, markers for astrocytes, microglia, and myelin were found to be labeled by means of immunocytochemistry in the corpus callosum, the internal capsule, and the optic tract. The ultrastructural integrity and oligodendrocyte density in the optic tract were investigated by electron microscopy. Quantitative analysis revealed that chronic cerebral hypoperfusion caused mild astrogliosis in the corpus callosum and the internal capsule, while astrocytic disintegration in the optic tract increased by 50%. Further, a ten-fold increase in microglial activation and a nearly doubled oligodendrocyte density were measured in the optic tract of the hypoperfused rats as compared with the controls. Finally, vacuolization and irregular myelin sheaths were observed at the ultrastructural level in the optic tract. In summary, the rat optic tract appears to be particularly vulnerable to ischemia, probably because of the rat brain's angioarchitecture. Since the detected glial changes correspond with those reported in vascular and Alzheimer dementia, this model of cerebral hypoperfusion may serve to characterize the causal relationship between ischemia and white matter damage.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalActa Neuropathologica
Volume108
Issue number1
DOIs
Publication statusPublished - Jul 2004

Fingerprint

Wounds and Injuries
Brain
Internal Capsule
Ischemia
Corpus Callosum
Oligodendroglia
Myelin Sheath
Vascular Dementia
Common Carotid Artery
Microglia
Neuroglia
Astrocytes
Dementia
Optic Tract
White Matter
Electron Microscopy
Alzheimer Disease
Immunohistochemistry

Keywords

  • Astrocyte
  • Cerebral hypoperfusion
  • Microglia
  • Optic tract
  • White matter

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Experimental cerebral hypoperfusion induces white matter injury and microglial activation in the rat brain. / Farkas, E.; Donka, Gergely; de Vos, Rob A I; Mihály, A.; Bari, F.; Luiten, Paul G M.

In: Acta Neuropathologica, Vol. 108, No. 1, 07.2004, p. 57-64.

Research output: Contribution to journalArticle

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