Astrocytes are more resistant to focal cerebral ischemia than neurons and die by a delayed necrosis


Gürer G., Gursoy-Ozdemir Y., ERDEMLİ E., CAN A., DALKARA T.

Brain Pathology, cilt.19, sa.4, ss.630-641, 2009 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 19 Sayı: 4
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1111/j.1750-3639.2008.00226.x
  • Dergi Adı: Brain Pathology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.630-641
  • Anahtar Kelimeler: Apoptosis, Astrocyte, Focal cerebral ischemia, Glycogen, Necrosis
  • Ankara Üniversitesi Adresli: Evet

Özet

Several recent reports proposed that astrocyte death might precede neuronal demise after focal ischemia, contrary to the conventional view that astrocytes are more resistant to injury than neurons. Interestingly, there are findings supporting each of these opposing views. To clarify these controversies, we assessed astrocyte viability after 2-h middle cerebral artery occlusion in mice. In contrast to neighboring neurons, astrocytes were alive and contained glycogen across the ischemic area 6 h after reperfusion, and at the expanding outer border of the infarct at later time points. These glycogen-positive astrocytes had intact plasma membranes. Astrocytes lost plasmalemma integrity much later than neurons: 19 ± 22 (mean ± standard deviation), 58 ± 14 and 69 ± 3% of astrocytes in the perifocal region became permeable to propidium iodide (PI) at 6, 24, 72 h after ischemia, respectively, in contrast to 81 ± 2, 96 ± 3, 97 ± 2% of neurons. Although more astrocytes in the cortical and subcortical core regions were PI-positive, their numbers were considerably less than those of neurons. Lysosomal rupture (monitored by deoxyribonuclease II immunoreactivity) followed a similar time course. Cytochrome-c immunohistochemistry showed that astrocytes maintained mitochondrial integrity longer than neurons. EM confirmed that astrocyte ultrastructure including mitochondria and lysosomes disintegrated much later than that of neurons. We also found that astrocytes died by a delayed necrosis without significantly activating apoptotic mechanisms although they rapidly swelled at the onset of ischemia. © 2008 International Society of Neuropathology.