Xu Lab

Excitotoxicity is the major cause of neuronal damage in many neurological disorders, including stroke and traumatic brain injury. Imbalance of excitation and inhibition also results in epilepsy. The excitablity of the brain is determined by synaptic transmission and neuronal membrane property. Recent study indicates that inflammation also plays an important role in neuronal injury in many neurological disorders. Researchers in the lab of Zao Xu, MD, PhD are working to understand the role of alteration of neuronal excitability in pathogenesis of neurological disorders.

Active Research

Stroke

Stroke is the leading cause of death and disability in U.S. Transient cerebral ischemia results in selective neuronal damage in the brain. A-type potassium current (IA) plays important role in maintaining neuronal excitability. The Xu’s lab demonstrated that enhancement of IA protects neurons against ischemia. The lab is investigating the PKC regulation of IA channels after ischemia using animal models of transient global ischemia and oxygen-glucose deprivation models of neuronal culture.  Diabetes exacerbates the ischemia outcome and increases the incidence of post-ischemia seizure/epilepsy.  Xu’s lab also reveal the mechanisms of epilepsy after ischemia in normoglycemic and diabetes conditions.

Seizure/epilepsy

Seizure/epilepsy is a common sequela of acute neurological disorders including stroke and traumatic brain injury. In addition to studying the excitability change after cerebral ischemia and TBI that might contribute to post traumatic epilepsy (PTE), researchers in the Xu Lab are also investigating the possible role of inflammation factors in PTE using animal models and patient data.

The 4-Vessel Occlusion (4-VO) model is used to induce transient cerebral ischemia, and Control Cortical Impact (CCI) model to induce TBI.  The techniques in Xu’s lab include in vivo and in vitro electrophysiological recording, such as intracellular recording the staining, patch-clamp recording on brain slices, cell culture and acute dissociated neurons; protein, DNA and RNA analysis, gene transfection in vivo and in vitro; and morphological techniques such as histological staining and immunocytochemical staining.

Research Funding

ISPBIF 020915 (Richard B Rodgers), Investigation of a Novel Hemoadsorption System in Rats with Traumatic Brain Injury application, 7/1/2015 – 6/30/2017, Co-PI

OTA (Todd McKinley), Decreasing systemic inflammation to improve fracture healing in polytraumatized rats, 01/01/2016 – 12/20/2019, Co-PI

ISPBIF 020915  (Zhigang Lei), The role of Sestrin 3-regulated inflammatory pathways in post-traumatic epilepsy, 7/1/2017 – 6/30/2019

Recent Publications

Xia, Zhigang Lei, Zhongshan Shi, Dave Guo, Henry Su, Yiwen Ruan, Zao C. Xu (2016) Enhanced autophagy signaling in post-ischemia seizures under diabetic conditions.  Brain Res. 1643:18-26.

Zhigang Lei, Hui Zhang, Yanling Liang, Zao C. Xu (2016) Reduced expression of IA channels is associated with post-ischemic seizures. Epilepsy Res. 124:40-48.

Lei, Z., Zhang, H., Liang, Y., Cui, Q., Xu, Z. and Xu, Z. C. (2014) Reduced expression of IA channels is associated with post-ischemic seizures in hyperglycemic rats.  J. Neurosci Res. 92:1775–1784.

Liang, Y., Lei, Z., Zhang, H., Xu, Z., Cui, Q. and Xu, Z.C. (2014) Toll-like receptor 4 is associated with seizures following ischemia with hyperglycemia. Brain Res. 1590: 75-84.

Deng, L., Deng, P., Ruan, Y., Xu, Z. C., Liu, N., Smith, G. and Xu, X. M. (2013) A Novel Growth-Promoting Pathway Formed by GDNF-Overexpressing Schwann Cells Promotes Propriospinal Axonal Regeneration, Synapse formation, and Partial Recovery of Function after Spinal Cord Injury.  J. Neurosci. 33:5655–5667.

Lei, Z., Deng, P., Li, J. and Xu, Z. C. (2012) Alterations of A-type potassium channels in hippocampal neurons after traumatic brain injury.  J Neurotrauma. 29: 235-245.

Ruan, Y., Han, X., Shi, Z., Lei, Z. and Xu, Z. C. (2012) Remodeling of synapses in the CA1 area of the hippocampus after transient global ischemia. Neurosci. 218: 268-277.

Deng, P., Pang, ZP., Lei, Z., Shikano, S., Xiong, Q., Harvey, B., London, B., Wang, Y., Li, M. and Xu, Z. C. (2011) Up-regulation of A-type potassium currents protects neurons against cerebral ischemia.  JCBFM 31: 1823-1835. Feature Article

Gao, X., Deng, P., Xu, Z. C., and Chen J. (2011) Moderate traumatic brain injury causes acute dendritic and synaptic degeneration in the hippocampal dentate gyrus. PLoS One. 6(9) e24566.

Faculty Research Team

Zao C. Xu, MD, PhD

Zao C. Xu, MD, PhD

Professor Emeritus of Anatomy & Cell Biology