[Effect of all-trans retinoic acid on cerebral ischemia injury and regulatory T cell accounts in stroke mice].

Abstract

OBJECTIVE:

To investigate the cerebral infarct volume 24 hours after transient middle cerebral artery occlusion (tMCAO) and the proportion of CD4⁺;CD25⁺;Foxp3⁺; regulatory T cells (Tregs) in splenocytes in diverse periods after all-trans retinoic acid (ATRA) treatment in mice, so as to explore whether ATRA have the protection against cerebral ischemia damage in mice through intervening Treg differentiation.

METHODS:

Sixty male Kunming mice were randomly divided into two groups, i.e. pretreatment (n=40) and post-treatment (n=20) groups. Each group was against divided into two subgroups, i.e. tMCAO combined with ATRA treatment group, tMCAO combined with DMSO control group. Pretreatment groups: mice were treated intraperitoneally with ATRA (10 mg/kg) dissolved in 100 mL/L DMSO or equivalent volume of 100 mL/L DMSO daily for 7 days (n=20/group). Ten mice in each group were sacrificed and the proportion of Tregs in splenocytes was analyzed by flow cytometry (FCM) after 7-day pretreatment. The other 10 mice in each group were subjected to tMCAO by modified monofilament method. Neurologic deficit score (NDS) was recorded and the infarct volume was assessed by 2, 3, 5-triphenyltetrazolium chloride(TTC) staining 24 hours after tMCAO. The mice in post-treatment groups were treated intraperitoneally with ATRA (10 mg/kg) or equivalent volume of 100 mL/L DMSO immediately after the reperfusion of tMCAO modeling (n=10/group). NDS and infarct volume were assessed and the proportion of Tregs in splenocytes was analyzed 24 hours after tMCAO.

RESULTS:

ATRA pretreatment for 7 days failed to improve neurologic function deficit (P>0.05) and to reduce the cerebral infarct volume (P>0.05) 24 hours after tMCAO in mice. ATRA post-treatment could markedly improve neurologic function (P<0.05) and reduce the cerebral infarct volume (P<0.05) 24 hours after tMCAO. However, neither ATRA pretreatment nor post-treatment had effect on the proportion of Tregs in the splenocytes of mice (P>0.05).

CONCLUSION:

ATRA administered before tMCAO for 7 days failed to protect brain against ischemic damage. ATRA administered immediately following tMCAO induced cerebral protective effect 24 hours after tMCAO. The results suggest that Tregs change is not involved in the neuroprotection mechanism of ATRA.

• Authors: Yanmei Yang, Shiquan Wang, Wenyuan Jia, Hailong Dong, Chen Wang
• Journal: Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology (Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi) Vol. 30 Issue 5 Pg. 458-61 (May 2014) ISSN: 1007-8738 [Print] China
• PMID: 24796737 (Publication Type: English Abstract, Journal Article)

Chemical References

• Neuroprotective Agents
• Tretinoin

Topics

• Animals
• Brain Ischemia (etiology, metabolism, prevention & control)
• Cerebral Infarction (etiology, metabolism, prevention & control)
• Flow Cytometry
• Infarction, Middle Cerebral Artery (complications)
• Male
• Mice
• Neuroprotective Agents (pharmacology)
• Random Allocation
• Spleen (drug effects, immunology, metabolism)
• Stroke (complications)
• T-Lymphocytes, Regulatory (drug effects, immunology, metabolism)
• Time Factors
• Tretinoin (pharmacology)