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Faculty Research Labs

Deng Lab

The overarching research focus of the laboratory of Lingxiao Deng, PhD is to augment our understanding of neural plasticity following spinal cord injury and provide the fundamental basis for promising new therapies. 

graphic illustration of neural network

Towards this goal, Dr. Deng’s work explores three important translational themes: the plasticity of neural circuitry mediating the recovery of bladder function after spinal cord injury; pharmacological approach to protect the spinal cord from contusive injury; and cell transplantation combined with locomotor exercise to improve the motor and bladder functional recovery after spinal cord injury. The main approaches utilized in the laboratory include animal model of spinal cord injury, cell transplantation, locomotor exercise, behavior evaluation, recombinant virus tracing the neural circuitry, urodynamic recording, histology, molecular biology, electrophysiology, mouse genetics and imaging.

Spinal cord injury results in significant impairment of motor, sensory and autonomic dysfunction, such as bladder function for the remainder of an individual’s life. It also increases the risk for numerous complications leading to increased morbidity and mortality. The biggest challenge to achieve functional recovery after spinal cord injury is to promote the regeneration of central nerve axons. Lack of supporting cellular matrix and inhibitory glial scar surrounding the lesion are two major barriers for axonal regeneration. Schwann cells are the supportive glial cell in peripheral nerves and considered to be one of the most promising cellular types for central nerve axonal regeneration. However, the therapeutic efficacy of Schwann cells is significantly limited because the grafted cells are often trapped within the lesion cavity by the glial scar and host astrocytes. One of Dr. Deng’s studies was the first to demonstrate that glial derived neurotrophic factor can reduce the glial scar at the interface between grafted Schwann cells and host astrocytes, significantly promoting axonal regeneration. This novel finding significantly extends our knowledge about the molecular mechanism of the glial derived neurotrophic factor's neuronal protective effects in several ways. Based on this finding, Dr. Deng established a Schwann cell-based continuous axonal growth—promoting pathway to successfully promote the regeneration of central nervous axons, particularly propriospinal axon to regenerate across the spinal cord lesion and led to the recovery of motor function.

Active Research

The neuroprotective effect of hypothermia has been demonstrated in both experimental and human spinal cord injury studies. Clinical trials have been initiated. However, the efficacy of the clinical application of hyperthermia to treat spinal cord injury remains significantly limited by delayed initiation of hypothermia in clinical practice. Dr. Deng has applied an FDA-approved and widely used clinic sedative drug rapidly induce up to 16 hours of moderate general hypothermia in ordinary ambient temperature without using any auxiliary cooling equipment. This early onset and long-lasting effect of hypothermia greatly improved both locomotor and bladder voiding functions. The current study focuses on verifying if this drug is superior to the conventional hypothermia in neuroprotection after spinal cord injury; uncovering the neuroprotective mechanism; and optimizing the therapeutic protocol of drug-induced hypothermia.

Bladder voiding dysfunction resulting from spinal cord injury can lead to severe complications such as renal failure, which is the major cause of morbidity and mortality among spinal cord injury patients. Recovery of bladder voiding is a top priority for spinal cord injury patients. So far, few effective therapies are available to target bladder function recovery. One major reason is the limited understanding of the mechanisms for both spontaneous and therapeutic functional recovery after spinal cord injury. Dr. Deng’s lab is working toward verifying a hypothesis that one population of propriospinal neurons participate in a spinal circuit to modulate external urethral sphincter activity and mediate the spontaneous recovery of  external urethral sphincter function after spinal cord injury.

Supraspinal axonal regeneration and innervation are both indispensable prerequisites for satisfactory urination functional recovery. Schwann cells are one of the most promising candidates facilitating axonal regeneration. Locomotor training prevents the dendritic atrophy of injured motoneuron. Dr. Deng’s strategy is to combine Schwann cell transplantation with locomotor training to promote supraspinal axonal regeneration and reinnervation on motoneurons to restore neural circuitry.

Published spinal cord injury studies in animals largely have employed a single sex design. Few reports in comparison have examined whether sex affects biochemical, anatomical or functional outcomes following spinal cord injury or have evaluated sex-based differences in response to therapy. Dr. Deng has found that male and female rats with spinal cord injury respond differently to the locomotor training. The mechanism responsible for this difference is unknown. His lab will apply large-molecule microdialysis to uncover sex-based different dynamic changes of these large-molecule factors in the process of locomotor training-affiliated functional recovery after spinal cord injury.

Research Team

18846-Deng, Lingxiao

Lingxiao Deng, M.D., PhD

Assistant Professor of Neurological Surgery

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65500-Khabbaz, Aytak

Aytak Khabbaz, MD

Postdoctoral Fellow in Neurological Surgery

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Samhita Chakraborty

Research Assistant

Kristen Cohen

Research Assistant

Yihong Zhang

Research Assistant

Shengqi Zhang

Visiting Student

Research Funding

Plasticity of spinal L3 propriospinal neurons in urination recovery after thoracic SCI 
NINDS
R21
9/22/2022 - 8/31/2024 
PI, Deng; co-I, Jin

Synergistically enhanced neuroprotection via Dexmedetomidine induced early hypothermia and ERK activation after spinal cord injury
Department of Defense
7/15/2023 - 7/14/2026
PI, Deng; co-I, Gao

Changes in inflammatory biomarkers from locomotor exercise-induced sex-based recovery after contusive spinal cord injury
Indiana Department of Health
7/1/2023 - 6/30/2025
PI, Deng; co-PI, Engleman

Combination of locomotor training and Schwann cell transplantation to promote the micturition function after contusive spinal cord injury
Indiana Department of Health
Jul 01, 2021 - Jun 30, 2024
PI, Deng

Publications

Liu NK, Deng LX, Wang M, Lu QB, Wang C, Wu X, Wu W, Wang Y, Qu W, Han Q, Xia Y, Ravenscraft B, Li JL, You SW, Wipf P, Han X, Xu XM. Restoring mitochondrial cardiolipin homeostasis reduces cell death and promotes recovery after spinal cord injury. Cell Death Dis. 2022 Dec 20;13(12):1058. doi: 10.1038/s41419-022-05369-5. PMID: 36539405.

Deng L, Ravenscraft B, Xu XM. Exploring propriospinal neuron-mediated neural circuit plasticity using recombinant viruses after spinal cord injury. Exp Neurol. 2022 Mar;349:113962. doi: 10.1016/j.expneurol.2021.113962. Epub 2021 Dec 22. PMID: 34953895..

Deng L, Sui T, Wang DV, Hou S, Cao X, Peng K, Xu Z, Xu X. Locomotor Exercise Enhances Supraspinal Control of Lower-Urinary-Tract Activity to Improve Micturition Function after Contusive Spinal-Cord Injury. Cells. 2022; 11(9):1398. https://doi.org/10.3390/cells11091398

Deng LX, Liu NK, Wen RN, Yang SN, Wen X, Xu XM. Laminin-coated multifilament entubulation, combined with Schwann cells and glial cell line-derived neurotrophic factor, promotes unidirectional axonal regeneration in a rat model of thoracic spinal cord hemisection. Neural Regen Res. 2021 Jan;16(1):186-191. doi: 10.4103/1673-5374.289436. PMID: 32788475; PMCID: PMC7818857.

Deng L, Ruan Y, Chen C, Frye CC, Xiong W, Jin X, Jones K, Sengelaub D, Xu XM. Characterization of dendritic morphology and neurotransmitter phenotype of thoracic descending propriospinal neurons after complete spinal cord transection and GDNF treatment. Exp Neurol. 2016 Mar;277:103-114. doi: 10.1016/j.expneurol.2015.12.018. Epub 2015 Dec 28. PMID: 26730519; PMCID: PMC4761305.

Deng LX, Walker Chandler, Xu XM, Schwann Cell-Mediated Axonal Regeneration in the Central Nervous System, Book “Neuronal regeneration”, Chapter , 2015, Academic Press,Pages 337-349,

Liu NK, Deng LX, Zhang YP, Lu QB, Wang XF, Hu JG, Oakes E, Bonventre JV, Shields CB, Xu XM. Cytosolic phospholipase A2 protein as a novel therapeutic target for spinal cord injury. Ann Neurol. 2014 May;75(5):644-58. doi: 10.1002/ana.24134. Epub 2014 Apr 2. PMID: 24623140; PMCID: PMC4320750.

Deng LX, Walker C, Xu XM. Schwann cell transplantation and descending propriospinal regeneration after spinal cord injury. Brain Res. 2015 Sep 4;1619:104-14. doi: 10.1016/j.brainres.2014.09.038. Epub 2014 Sep 26. PMID: 25257034; PMCID: PMC4375094.

Deng LX, Deng P, Ruan Y, Xu ZC, Liu NK, Wen X, Smith GM, Xu XM. 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. 2013 Mar 27;33(13):5655-67. doi: 10.1523/JNEUROSCI.2973-12.2013. PMID: 23536080; PMCID: PMC3664932.

Deng LX, Hu J, Liu N, Wang X, Smith GM, Wen X, Xu XM. GDNF modifies reactive astrogliosis allowing robust axonal regeneration through Schwann cell-seeded guidance channels after spinal cord injury. Exp Neurol. 2011 Jun;229(2):238-50. doi: 10.1016/j.expneurol.2011.02.001. Epub 2011 Feb 21. PMID: 21316362; PMCID: PMC3100372. (Cover paper)