The main objective of this project is a study of synaptic plasticity viewed in postischemic neurons and a new mechanisms for ischemic neuronal damage. The principal investigator has recently found that ultrastructure of postsynaptic densities (PSDs) is highly modified following a brief ischemic episode. The structural modification is coordinated with tight anchoring of new signal transduction molecules, substantial alterations of molecular composition and protein phosphorylation in the PSDs. Ischemia is a nonspecific stimulus and it is hypothesized that structural and molecular modification of PSDs following stimulation is a fundamental process of the CNS; i.e., a structural and molecular basis for increased strength of neurotransmission (long term potentiation). However, this process if excessive may amplify the signal pathologically and cause neuronal dysfunction or even neuronal death.
The Specific Aims are: 1. to further study structural and molecular modification of PSDs in postischemic neurons by EM and EM tomography and by biochemical methods; 2. to study time courses of the structural and molecular modification of PSDs using the brains with systemically varied reperfusion and ischemic duration; 3. to study the mechanisms of receptor aggregation. Although glutamate antagonists are neuroprotective in ischemic stroke, they usually cause severe side effects. Understanding structural and molecular modification of PSDs that leads to postischemic enhancement of glutamate transmission may provide a new avenue to protect neuron against stroke. It may also contribute to understanding of fundamental principle of synaptic plasticity.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-NLS-3 (01))
Program Officer
Jacobs, Tom P
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Queen's Medical Center
United States
Zip Code
Yuan, Dong; Liu, Chunli; Wu, Jiang et al. (2018) Inactivation of NSF ATPase Leads to Cathepsin B Release After Transient Cerebral Ischemia. Transl Stroke Res 9:201-213
Yuan, Dong; Liu, Chunli; Hu, Bingren (2018) Dysfunction of Membrane Trafficking Leads to Ischemia-Reperfusion Injury After Transient Cerebral Ischemia. Transl Stroke Res 9:215-222
Sun, Xin; Crawford, Robert; Liu, Chunli et al. (2015) Development-dependent regulation of molecular chaperones after hypoxia-ischemia. Neurobiol Dis 82:123-131
Park, Yujung; Liu, Chunli; Luo, Tianfei et al. (2015) Chaperone-Mediated Autophagy after Traumatic Brain Injury. J Neurotrauma 32:1449-57
Zhang, Fan; Guo, Ailan; Liu, Chunli et al. (2013) Phosphorylation and assembly of glutamate receptors after brain ischemia. Stroke 44:170-6
Luo, Tianfei; Park, Yujung; Sun, Xin et al. (2013) Protein misfolding, aggregation, and autophagy after brain ischemia. Transl Stroke Res 4:581-8
Ge, Pengfei; Zhang, Fan; Zhao, Jingwei et al. (2012) Protein degradation pathways after brain ischemia. Curr Drug Targets 13:159-65
Liu, Chunli; Gao, Yanqin; Barrett, John et al. (2010) Autophagy and protein aggregation after brain ischemia. J Neurochem 115:68-78
Truettner, Jessie S; Hu, Kurt; Liu, Cindy L et al. (2009) Subcellular stress response and induction of molecular chaperones and folding proteins after transient global ischemia in rats. Brain Res 1249:9-18