PMID- 36858281
OWN - NLM
STAT- MEDLINE
DCOM- 20230405
LR  - 20230407
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 363
DP  - 2023 May
TI  - Hydralazine plays an immunomodulation role of pro-regeneration in a mouse model 
      of spinal cord injury.
PG  - 114367
LID - S0014-4886(23)00051-1 [pii]
LID - 10.1016/j.expneurol.2023.114367 [doi]
AB  - Spinal cord injury (SCI) results in severe motor and sensory dysfunction with no 
      effective therapy. Spinal cord debris (sp) from injured spinal cord evokes 
      secondary SCI continuously. We and other researchers have previously clarified 
      that it is mainly bone marrow derived macrophages (BMDMs) infiltrating in the 
      lesion epicenter to clear sp, rather than local microglia. Unfortunately, the 
      pro-inflammatory phenotype of these infiltrating BMDMs is predominant which 
      impairs wound healing. Hydralazine, as a potent vasodilator and scavenger of 
      acrolein, has protective effects in many diseases. Hydralazine is also confirmed 
      to promote motor function and hypersensitivity in SCI rats through scavenging 
      acrolein. However, few studies have explored the effects of hydralazine on 
      immunomodulation, as well as spontaneous pain and emotional response, the 
      important syndromes in clinical patients. It remains unclear whether hydralazine 
      affects infiltrating BMDMs after SCI. In this study, we targeted BMDMs to explore 
      the influence of hydralazine on immune cells in a mouse model of SCI, and also 
      investigated the contribution of polarized BMDMs to hydralazine-induced 
      neurological function recovery after SCI in male mice. The adult male mice 
      underwent T10 spinal cord compression. The results showed that in addition to 
      improving motor function and hypersensitivity, hydralazine relieved SCI-induced 
      spontaneous pain and emotional response, which is a newly discovered function of 
      hydralazine. Hydralazine inhibited the recruitments of pro-inflammatory BMDMs and 
      educated infiltrated BMDMs to a more reparative phenotype involving in multiple 
      biological processes associated with SCI pathology, including immune/inflammation 
      response, neurogenesis, lipid metabolism, oxidative stress, fibrosis formation, 
      and angiogenesis, etc. As an overall effect, hydralazine-treated BMDMs loaden 
      with sp partially rescued neurological function after SCI. It is concluded that 
      hydralazine plays an immunomodulation role of educating pro-inflammatory BMDMs to 
      a more reparative phenotype; and hydralazine-educated BMDMs contribute to 
      hydralazine-induced improvement of neurological function in SCI mice, which 
      provides support for drug and cell treatment options for SCI therapy.
CI  - Copyright (c) 2023. Published by Elsevier Inc.
FAU - Quan, Xin
AU  - Quan X
AD  - Institute of Neurosciences and Department of Neurobiology, Fourth Military 
      Medical University, Xi'an 710032, China.
FAU - Yu, Caiyong
AU  - Yu C
AD  - Institute of Neurosciences and Department of Neurobiology, Fourth Military 
      Medical University, Xi'an 710032, China; Military Medical Innovation Center, 
      Fourth Military Medical University, Xi'an 710032, China.
FAU - Fan, Zhongmin
AU  - Fan Z
AD  - Department of Critical Care Medicine and Department of Anesthesiology and 
      Perioprative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 
      710032, China.
FAU - Wu, Tong
AU  - Wu T
AD  - Institute of Neurosciences and Department of Neurobiology, Fourth Military 
      Medical University, Xi'an 710032, China.
FAU - Qi, Chuchu
AU  - Qi C
AD  - Institute of Neurosciences and Department of Neurobiology, Fourth Military 
      Medical University, Xi'an 710032, China.
FAU - Zhang, Haoying
AU  - Zhang H
AD  - Institute of Neurosciences and Department of Neurobiology, Fourth Military 
      Medical University, Xi'an 710032, China.
FAU - Wu, Shengxi
AU  - Wu S
AD  - Institute of Neurosciences and Department of Neurobiology, Fourth Military 
      Medical University, Xi'an 710032, China. Electronic address: shengxi@fmmu.edu.cn.
FAU - Wang, Xi
AU  - Wang X
AD  - Institute of Neurosciences and Department of Neurobiology, Fourth Military 
      Medical University, Xi'an 710032, China; The College of Life Sciences and 
      Medicine, Northwest University, Xi'an 710069, China. Electronic address: 
      wangzh@fmmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230228
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 7864XYD3JJ (Acrolein)
RN  - 26NAK24LS8 (Hydralazine)
SB  - IM
MH  - Rats
MH  - Mice
MH  - Male
MH  - Animals
MH  - *Acrolein/metabolism
MH  - *Spinal Cord Injuries/complications/drug therapy/metabolism
MH  - Macrophages/metabolism
MH  - Hydralazine/pharmacology/therapeutic use/metabolism
MH  - Spinal Cord/pathology
MH  - Pain/metabolism
OTO - NOTNLM
OT  - Bone marrow derived macrophages
OT  - Emotion
OT  - Hydralazine
OT  - Immunomodulation
OT  - Pro-inflammatory
OT  - Pro-regeneration
OT  - Spinal cord injury
OT  - Spontaneous pain
COIS- Declaration of Competing Interest None.
EDAT- 2023/03/02 06:00
MHDA- 2023/04/05 06:42
CRDT- 2023/03/01 19:26
PHST- 2022/08/30 00:00 [received]
PHST- 2023/02/09 00:00 [revised]
PHST- 2023/02/24 00:00 [accepted]
PHST- 2023/04/05 06:42 [medline]
PHST- 2023/03/02 06:00 [pubmed]
PHST- 2023/03/01 19:26 [entrez]
AID - S0014-4886(23)00051-1 [pii]
AID - 10.1016/j.expneurol.2023.114367 [doi]
PST - ppublish
SO  - Exp Neurol. 2023 May;363:114367. doi: 10.1016/j.expneurol.2023.114367. Epub 2023 
      Feb 28.