Neurochemical Research

, Volume 43, Issue 7, pp 1348–1362 | Cite as

Cellular and Subcellular Localization of Endoplasmic Reticulum Chaperone GRP78 Following Transient Focal Cerebral Ischemia in Rats

  • Xuyan Jin
  • Dong Kyu Kim
  • Tae-Ryong Riew
  • Hong Lim Kim
  • Mun-Yong Lee
Original Paper


The 78-kDa glucose-regulated protein (GRP78), a chaperone protein located in the endoplasmic reticulum (ER), has been reported to have neuroprotective effects in the injured central nervous system. Our aim was to examine the expression profiles and subcellular distributions of GRP78 and its association with the neuroglial reaction in the rat striatum after transient, focal cerebral ischemia. In sham-operated rats, constitutive, specific immunoreactivity for GRP78 was almost exclusively localized to the rough ER of striatal neurons, with none in the resting, ramified microglia or astrocytes. At 1 day post reperfusion, increased expression was observed in ischemia-resistant cholinergic interneurons, when most striatal neurons had lost GRP78 expression (this occurred earlier than the loss of other neuronal markers). By 3 days post reperfusion, GRP78 expression had re-emerged in association with the activation of glial cells in both infarct and peri-infarct areas but showed different patterns in the two regions. Most of the expression induced in the infarct area could be attributed to brain macrophages, while expression in the peri-infarct area predominantly occurred in neurons and reactive astrocytes. A gradual, sustained induction of GRP78 immunoreactivity occurred in reactive astrocytes localized to the astroglial scar, lasting for at least 28 days post reperfusion. Using correlative light- and electron-microscopy, we found conspicuous GRP78 protein localized to abnormally prominent, dilated rough ER in both glial cell types. Thus, our data indicate a link between GRP78 expression and the activated functional status of neuroglial cells, predominantly microglia/macrophages and astrocytes, occurring in response to ischemia-induced ER stress.


78-KDa glucose-regulated protein Striatum Endoplasmic reticulum Stroke Neuron Glial cells 



Analysis of variance


Immunoglobulin heavy-chain binding protein


Choline acetyltransferase


Central nervous system


3,3′-diaminobenzidine tetrahydrochloride




Endoplasmic reticulum


Glial fibrillary acidic protein


78-kDa glucose-regulated protein




Ionized calcium-binding adaptor molecule 1


Middle cerebral artery


Middle cerebral artery occlusion


Neuronal nuclear protein


Phosphate buffer


Sodium dodecyl sulfate


Standard error of the mean


Terminal deoxynucleotidyl transferase dUTP nick end labelling


Unfolded protein response



This research was supported by the National Research Foundation of Korea (NRF) [Grant Number NRF-2017R1A2B4002922].

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Xuyan Jin
    • 1
  • Dong Kyu Kim
    • 1
  • Tae-Ryong Riew
    • 1
  • Hong Lim Kim
    • 2
  • Mun-Yong Lee
    • 1
  1. 1.Department of Anatomy, Catholic Neuroscience Institute, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
  2. 2.Integrative Research Support Center, Laboratory of Electron Microscopy, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea

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