The neuron-astrocyte-microglia triad in CA3 after chronic cerebral hypoperfusion in the rat: Protective effect of dipyridamole

Exp Gerontol. 2017 Oct 1:96:46-62. doi: 10.1016/j.exger.2017.06.006. Epub 2017 Jun 9.

Abstract

We investigated the quantitative and morphofunctional alterations of neuron-astrocyte-microglia triads in CA3 hippocampus, in comparison to CA1, after 2 Vessel Occlusion (2VO) and the protective effect of dipyridamole. We evaluated 3 experimental groups: sham-operated rats (sham, n=15), 2VO-operated rats treated with vehicle (2VO-vehicle, n=15), and 2VO-operated rats treated with dipyridamole from day 0 to day 7 (2VO-dipyridamole, n=15), 90days after 2VO. We analyzed Stratum Pyramidalis (SP), Stratum Lucidum (SL) and Stratum Radiatum (SR) of CA3. 1) ectopic neurons increased in SL and SR of 2VO-vehicle, and 2VO-dipyridamole rats; 2) apoptotic neurons increased in SP of 2VO-vehicle rats and dipyridamole reverted this effect; 3) astrocytes increased in SP, SL and SR of 2VO-vehicle and 2VO-dipyridamole rats; 4) TNF-α expression increased in astrocytes, blocked by dipyridamole, and in dendrites in SR of 2VO-vehicle rats; 5) total microglia increased in SL and SR of 2VO-vehicle and 2VO-dipyridamole rats; 6) triads increased in SR of 2VO-vehicle rats and dipyridamole reverted this effect. Microglia cooperated with astrocytes to phagocytosis of apoptotic neurons and debris, and engulfed ectopic non-fragmented neurons in SL of 2VO-vehicle and 2VO-dipyridamole rats, through a new mechanism called phagoptosis. CA3 showed a better adaptive capacity than CA1 to the ischemic insult, possibly due to the different behaviour of astrocytes and microglial cells. Dipyridamole had neuroprotective effects.

Keywords: Apoptosis; CA3; Confocal microscopy; Neuron-astrocyte-microglia triad; Phagocytosis; Phagoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Apoptosis / drug effects
  • Astrocytes / drug effects*
  • Brain Ischemia / physiopathology
  • CA3 Region, Hippocampal / cytology
  • CA3 Region, Hippocampal / drug effects
  • Carotid Artery, Common / surgery
  • Carotid Stenosis / physiopathology
  • Cerebrovascular Circulation / drug effects*
  • Dipyridamole / pharmacology*
  • Male
  • Microglia / drug effects*
  • Microscopy, Confocal
  • Neurons / drug effects*
  • Phagocytosis / drug effects
  • Pyramidal Cells / drug effects
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / metabolism
  • Vasodilator Agents / pharmacology*

Substances

  • Tumor Necrosis Factor-alpha
  • Vasodilator Agents
  • Dipyridamole