Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion

Comparison between normotensive and spontaneously hypertensive rats

Makoto Masumura, Ryuji Hata, Yasuo Nagai, Tohru Sawada

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

We investigated the neuropathological and biochemical changes in the white matter of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) after bilateral carotid artery ligation (BCAL). One week after BCAL, both WKY and SHR showed white matter rarefaction and vacuolation with reduced oligodendrocytes, but there was no difference between WKY and SHR. On the other hand, vacuoles formed by oligodendroglial cell death were increased significantly from 2 to 4 weeks in the optic tract and fimbria fornix of hypoperfused SHR. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end labeling (TUNEL)-positive cells and lectin-positive microglia increased in number and intensities of staining more markedly in SHR than in WKY. In situ cell death detection ELISA supported these results quantitatively. RT-PCR represented the expression of TNF-α, TNF receptor 1 (p55), caspase-2 (Ich-1) and -3 (CPP32) mRNAs in both WKY and SHR brains after BCAL. Immunohistochemical analyses revealed that TNF-α, TNF receptor 1 (p55), Ich-1 and CPP32 immunoreactive cells could also be detected in the white matter regions of hypoperfused SHR. These results suggested that local production of TNF-α by the activated microglia might selectively induce oligodendroglial cell death through the death domain-containing TNF receptor 1 (p55), caspase-2 or -3 activation, resulting in white matter changes as a primary pathological feature.

Original languageEnglish
Pages (from-to)401-412
Number of pages12
JournalNeuroscience Research
Volume39
Issue number4
DOIs
Publication statusPublished - 26-03-2001
Externally publishedYes

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DNA Fragmentation
Inbred SHR Rats
Cell Death
Carotid Arteries
Caspase 2
Ligation
In Situ Nick-End Labeling
Microglia
Brain Fornix
DNA Nucleotidylexotransferase
Oligodendroglia
Vacuoles
White Matter
Lectins
Enzyme-Linked Immunosorbent Assay
Staining and Labeling
Polymerase Chain Reaction
Messenger RNA
Brain
recombinant human tumor necrosis factor-binding protein-1

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

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abstract = "We investigated the neuropathological and biochemical changes in the white matter of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) after bilateral carotid artery ligation (BCAL). One week after BCAL, both WKY and SHR showed white matter rarefaction and vacuolation with reduced oligodendrocytes, but there was no difference between WKY and SHR. On the other hand, vacuoles formed by oligodendroglial cell death were increased significantly from 2 to 4 weeks in the optic tract and fimbria fornix of hypoperfused SHR. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end labeling (TUNEL)-positive cells and lectin-positive microglia increased in number and intensities of staining more markedly in SHR than in WKY. In situ cell death detection ELISA supported these results quantitatively. RT-PCR represented the expression of TNF-α, TNF receptor 1 (p55), caspase-2 (Ich-1) and -3 (CPP32) mRNAs in both WKY and SHR brains after BCAL. Immunohistochemical analyses revealed that TNF-α, TNF receptor 1 (p55), Ich-1 and CPP32 immunoreactive cells could also be detected in the white matter regions of hypoperfused SHR. These results suggested that local production of TNF-α by the activated microglia might selectively induce oligodendroglial cell death through the death domain-containing TNF receptor 1 (p55), caspase-2 or -3 activation, resulting in white matter changes as a primary pathological feature.",
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Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion : Comparison between normotensive and spontaneously hypertensive rats. / Masumura, Makoto; Hata, Ryuji; Nagai, Yasuo; Sawada, Tohru.

In: Neuroscience Research, Vol. 39, No. 4, 26.03.2001, p. 401-412.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion

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AU - Masumura, Makoto

AU - Hata, Ryuji

AU - Nagai, Yasuo

AU - Sawada, Tohru

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