PMID- 38527023
OWN - NLM
STAT- MEDLINE
DCOM- 20240327
LR  - 20240327
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 19
IP  - 3
DP  - 2024
TI  - Retinoic acid attenuates ischemic injury-induced activation of glial cells and 
      inflammatory factors in a rat stroke model.
PG  - e0300072
LID - 10.1371/journal.pone.0300072 [doi]
LID - e0300072
AB  - Stroke is a leading cause of death and long-term disability which can cause 
      oxidative damage and inflammation of the neuronal cells. Retinoic acid is an 
      active metabolite of vitamin A that has various beneficial effects including 
      antioxidant and anti-inflammatory effects. In this study, we investigated whether 
      retinoic acid modulates oxidative stress and inflammatory factors in a stroke 
      animal model. A middle cerebral artery occlusion (MCAO) was performed on adult 
      male rats to induce focal cerebral ischemia. Retinoic acid (5 mg/kg) or vehicle 
      was injected into the peritoneal cavity for four days before MCAO surgery. The 
      neurobehavioral tests were carried out 24 h after MCAO and cerebral cortex 
      tissues were collected. The cortical damage was assessed by hematoxylin-eosin 
      staining and reactive oxygen species assay. In addition, Western blot and 
      immunohistochemical staining were performed to investigate the activation of 
      glial cells and inflammatory cytokines in MCAO animals. Ionized calcium-binding 
      adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) were used 
      as markers of microglial and astrocyte activation, respectively. Tumor necrosis 
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were used as representative 
      pro-inflammatory cytokines. Results showed that MCAO damage caused 
      neurobehavioral defects and histopathological changes in the ischemic region and 
      increased oxidative stress. Retinoic acid treatment reduced these changes caused 
      by MCAO damage. We detected increases in Iba-1 and GFAP in MCAO animals treated 
      with vehicle. However, retinoic acid alleviated increases in Iba-1 and GFAP 
      caused by MCAO damage. Moreover, MCAO increased levels of nuclear factor-kappaB and 
      pro-inflammatory cytokines, including TNF-alpha and IL-1beta. Retinoic acid alleviated 
      the expression of these inflammatory proteins. These findings elucidate that 
      retinoic acid regulates microglia and astrocyte activation and modulates 
      pro-inflammatory cytokines. Therefore, this study suggests that retinoic acid 
      exhibits strong antioxidant and anti-inflammatory properties by reducing 
      oxidative stress, inhibiting neuroglia cell activation, and preventing the 
      increase of pro-inflammatory cytokines in a cerebral ischemia.
CI  - Copyright: (c) 2024 Kang et al. This is an open access article distributed under 
      the terms of the Creative Commons Attribution License, which permits unrestricted 
      use, distribution, and reproduction in any medium, provided the original author 
      and source are credited.
FAU - Kang, Ju-Bin
AU  - Kang JB
AD  - Department of Anatomy and Histology, College of Veterinary Medicine, Research 
      Institute of Life Science, Gyeongsang National University, Jinju, South Korea.
FAU - Son, Hyun-Kyoung
AU  - Son HK
AD  - Department of Anatomy and Histology, College of Veterinary Medicine, Research 
      Institute of Life Science, Gyeongsang National University, Jinju, South Korea.
FAU - Shah, Murad-Ali
AU  - Shah MA
AD  - Department of Anatomy and Histology, College of Veterinary Medicine, Research 
      Institute of Life Science, Gyeongsang National University, Jinju, South Korea.
FAU - Koh, Phil-Ok
AU  - Koh PO
AUID- ORCID: 0000-0003-0091-8287
AD  - Department of Anatomy and Histology, College of Veterinary Medicine, Research 
      Institute of Life Science, Gyeongsang National University, Jinju, South Korea.
LA  - eng
PT  - Journal Article
DEP - 20240325
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 5688UTC01R (Tretinoin)
RN  - 0 (Antioxidants)
RN  - 0 (Cytokines)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Neuroprotective Agents)
SB  - IM
MH  - Rats
MH  - Male
MH  - Animals
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Tretinoin/pharmacology/therapeutic use
MH  - Antioxidants/pharmacology/therapeutic use
MH  - *Stroke/drug therapy/metabolism
MH  - *Brain Ischemia/drug therapy
MH  - Neuroglia/metabolism
MH  - Cytokines/metabolism
MH  - Anti-Inflammatory Agents/therapeutic use
MH  - Infarction, Middle Cerebral Artery/complications/drug therapy/pathology
MH  - *Neuroprotective Agents/pharmacology/therapeutic use
PMC - PMC10962821
COIS- The authors have declared that no competing interests exist.
EDAT- 2024/03/25 18:42
MHDA- 2024/03/27 06:43
PMCR- 2024/03/25
CRDT- 2024/03/25 13:33
PHST- 2023/06/17 00:00 [received]
PHST- 2024/02/20 00:00 [accepted]
PHST- 2024/03/27 06:43 [medline]
PHST- 2024/03/25 18:42 [pubmed]
PHST- 2024/03/25 13:33 [entrez]
PHST- 2024/03/25 00:00 [pmc-release]
AID - PONE-D-23-18108 [pii]
AID - 10.1371/journal.pone.0300072 [doi]
PST - epublish
SO  - PLoS One. 2024 Mar 25;19(3):e0300072. doi: 10.1371/journal.pone.0300072. 
      eCollection 2024.