Neurodegeneration, Myelin Loss and Glial Response in the Three-Vessel Global Ischemia Model in Rat

International Journal of Molecular Sciences

卷:21

Tatiana Anan’ina¹  Alena Kisel¹  Marina Khodanovich¹  Konstantin Usov¹  Elena Krutenkova¹  Marina Kudabaeva¹  Vera Smolyakova²  Mark Plotnikov²  Galina Chernysheva² 

[1] Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, Lenina Ave., 634050 Tomsk, Russia;

[2] Laboratory of Pharmacology of Blood Circulation, E. D. Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Lenina Ave., 634028 Tomsk, Russia;

关键词: global cerebral ischemia;    GCI;    hippocampus;    CA1;    neurodegeneration;    myelin;   

DOI  :  10.3390/ijms21176246

来源: DOAJ

【 摘 要 】

(1) Background: Although myelin disruption is an integral part of ischemic brain injury, it is rarely the subject of research, particularly in animal models. This study assessed for the first time, myelin and oligodendrocyte loss in a three-vessel model of global cerebral ischemia (GCI), which causes hippocampal damage. In addition, we investigated the relationships between demyelination and changes in microglia and astrocytes, as well as oligodendrogenesis in the hippocampus; (2) Methods: Adult male Wistar rats (n = 15) underwent complete interruption of cerebral blood flow for 7 min by ligation of the major arteries supplying the brain or sham-operation. At 10 and 30 days after the surgery, brain slices were stained for neurodegeneration with Fluoro-Jade C and immunohistochemically to assess myelin content (MBP+ percentage of total area), oligodendrocyte (CNP+ cells) and neuronal (NeuN+ cells) loss, neuroinflammation (Iba1+ cells), astrogliosis (GFAP+ cells) and oligodendrogenesis (NG2+ cells); (3) Results: 10 days after GCI significant myelin and oligodendrocyte loss was found only in the stratum oriens and stratum pyramidale. By the 30th day, demyelination in these hippocampal layers intensified and affected the substratum radiatum. In addition to myelin damage, activation and an increase in the number of microglia and astrocytes in the corresponding layers, a loss of the CA1 pyramidal neurons, and neurodegeneration in the neocortex and thalamus was observed. At a 10-day time point, we observed rod-shaped microglia in the substratum radiatum. Parallel with ongoing myelin loss on the 30th day after ischemia, we found significant oligodendrogenesis in demyelinated hippocampal layers; (4) Conclusions: Our study showed that GCI-simulating cardiac arrest in humans—causes not only the loss of pyramidal neurons in the CA1 field, but also the myelin loss of adjacent layers of the hippocampus.

【 授权许可】

Unknown