The objective of this project is to investigate molecular mechanisms of synaptic damage and plasticity after transient cerebral ischemia (TCI). TCI selectively causes delayed neuronal death and leads to neurological deficits. Neurological functional recovery after stroke, which requires precise cell-to-cell communication through synapses, is a key issue for stroke patients. Therefore, studies of morphological and molecular alterations of synapses are relevant to understanding the mechanisms of ischemic neuronal loss and neurological outcome. However, very few studies on changes in synapses after ischemia have been conducted. We have recently established a series of techniques to study synaptic changes after brain insults, and found dramatic ultrastructural and biochemical alterations of synapses after TCI. The focus of the present proposal is to extend our previous studies and to propose new studies on synaptic remodeling after TCI. We will test a general hypothesis that progressive synaptic damage develops due both to damage induced by the ischemic event and to the lack of synaptic repair mediated by the ERK-CREB signaling cascade in ischemically vulnerable neurons after transient cerebral ischemia.
The specific aims are: 1. To study the synaptic alterations in multiple brain regions after various ischemic durations. 2. To investigate molecular reorganization of synapses after ischemia. 3. To study the regulatory role of the ERK-CREB cascade in synaptic remodeling after ischemia. Synaptic transmission is a very plastic process that is regulated via morphological changes, biochemical modification and molecular remodeling. Severe brain insults can damage synapses and induce neurological dysfunction. Understanding synaptic plasticity and damage after ischemia are key to develop therapeutic interventions. In this application, we propose studies to investigate synaptic damage and plasticity after brain ischemia.
| 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 |
| Luo, Tianfei; Roman, Philip; Liu, Chunli et al. (2015) Upregulation of the GEF-H1 pathway after transient cerebral ischemia. Exp Neurol 263:306-13 |
| 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 |
| Degracia, Donald; Hu, Bingren (2013) Protein misfolding and organelle stress after brain ischemia. Transl Stroke Res 4:579-80 |
| 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 |
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