Involvement of IL-17 in Secondary Brain Injury After a Traumatic Brain Injury in Rats

Tan Li; Yong-Mei Zhang; Dong Han; Rong Hua; Bing-Nan Guo; Shu-Qun Hu; Xian-Liang Yan; Tie Xu

doi:10.1007/s12017-017-8468-4

Involvement of IL-17 in Secondary Brain Injury After a Traumatic Brain Injury in Rats

Neuromolecular Med. 2017 Dec;19(4):541-554. doi: 10.1007/s12017-017-8468-4. Epub 2017 Sep 15.

Authors

Tan Li^{1

2}, Yong-Mei Zhang³, Dong Han¹, Rong Hua^{1

4}, Bing-Nan Guo¹, Shu-Qun Hu⁵, Xian-Liang Yan^{6

7}, Tie Xu^{8

9}

Affiliations

¹ Institute of Emergency Rescue Medicine, Xuzhou Medical University, Xuzhou, 221002, China.
² Jiangsu Province Second Hospital of TCM, Nanjing University of Traditional Chinese Medicine, Nanjing, 210017, China.
³ Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, 221004, China.
⁴ Emergency Center of the Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China.
⁵ Institute of Emergency Rescue Medicine, Xuzhou Medical University, Xuzhou, 221002, China. hushuqun88@126.com.
⁶ Institute of Emergency Rescue Medicine, Xuzhou Medical University, Xuzhou, 221002, China. docyxl@163.com.
⁷ Emergency Center of the Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China. docyxl@163.com.
⁸ Institute of Emergency Rescue Medicine, Xuzhou Medical University, Xuzhou, 221002, China. xutie889@163.com.
⁹ Emergency Center of the Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China. xutie889@163.com.

PMID: 28916896
DOI: 10.1007/s12017-017-8468-4

Abstract

The pro-inflammatory activity of interleukin 17, which is produced by the IL-23/IL-17 axis, has been associated with the pathogenesis of traumatic brain injury (TBI). The study investigated the potential role of IL-17 in secondary brain injury of TBI in a rat model. Our data showed that the levels of IL-17 increased from 6 h to 7 days and peaked at 3 days, in both the CNS and serum, which were consistent with the severity of secondary brain injury. The IL-23 inhibitor suberoylanilide hydroxamic acid (SAHA) treatment markedly decreased the expressions of IL-17 and apoptosis-associated proteins cleaved caspase-3 and increased the protein ratio of Bcl-2 (B cell lymphoma/leukemia-2)/Bax (Bcl-2-associated X protein). Meanwhile, neuronal apoptosis was reduced, and neural function was improved after SAHA treatment. This study suggests that IL-17 is involved in secondary brain injury after TBI. Administering an IL-23 inhibitor and thereby blocking the IL-23/IL-17 axis may be beneficial in the treatment of TBI.

Keywords: IL-17; IL-23/IL-17 axis; Inflammation; Secondary brain injury; TBI.

MeSH terms

Animals
Apoptosis / drug effects
Apoptosis Regulatory Proteins / biosynthesis
Apoptosis Regulatory Proteins / genetics
Brain Damage, Chronic / etiology
Brain Damage, Chronic / metabolism
Brain Damage, Chronic / physiopathology*
Brain Damage, Chronic / prevention & control
Brain Injuries, Traumatic / complications
Brain Injuries, Traumatic / drug therapy
Brain Injuries, Traumatic / metabolism
Brain Injuries, Traumatic / physiopathology*
Down-Regulation / drug effects
Hydroxamic Acids / pharmacology
Hydroxamic Acids / therapeutic use
Inflammation
Interleukin-17 / blood
Interleukin-17 / cerebrospinal fluid
Interleukin-17 / genetics
Interleukin-17 / physiology*
Interleukin-23 / antagonists & inhibitors
Interleukin-23 / physiology
Male
Nerve Tissue Proteins / biosynthesis
Nerve Tissue Proteins / blood
Nerve Tissue Proteins / cerebrospinal fluid
Nerve Tissue Proteins / genetics
Neurons / pathology
Neuroprotective Agents / pharmacology
Neuroprotective Agents / therapeutic use
Rats
Rats, Sprague-Dawley
Time Factors
Vorinostat

Substances

Apoptosis Regulatory Proteins
Hydroxamic Acids
Il17a protein, rat
Interleukin-17
Interleukin-23
Nerve Tissue Proteins
Neuroprotective Agents
Vorinostat