Logo-ps
Pharm Sci. 2024;30(4): 502-511.
doi: 10.34172/PS.2024.28
  Abstract View: 27
  PDF Download: 61

Research Article

Cerebral Ischemia-Reperfusion Induced Neuronal Damage, Inflammation, miR-374a-5p, MAPK6, NLRP3, and Smad6 Alterations: Rescue Effect of N-acetylcysteine

Hamed Saniei 1 ORCID logo, Alireza Shirpoor 2,3, Roya Naderi 4,3* ORCID logo

1 Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.
2 Nephrology and Kidney Transplant Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
3 Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
4 Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
*Corresponding Author: Roya Naderi, Email: naderi.r@umsu.ac.ir

Abstract

Background: Ischemic stroke (IS) is still a major cause of neurological disability. This study aimed to ascertain potential markers closely related to IS diagnosis and treatment and then we examined the neuroprotective effect of N-acetylcysteine (NAC) in a transient cerebral ischemia.

Methods: Male Wistar rats were randomly divided into three groups (n=6), including sham, IR (ischemia-reperfusion), IR+NAC (150 mg/kg, ip; intraperitoneally, 1 hour prior to ischemia and 5 min before reperfusion). The infarct volume was evaluated by 2,3,5-triphenyl tetrazolium chloride staining. H&E and Nissle staining were performed to evaluate cerebral ischemia-reperfusion injury. miR-374a-5p gene expression, MAPK6, NLRP3, smad6, TNF-α, and IL-1β protein levels were determined by Real-time PCR, Western blot, and Elisa in the cerebral cortex exposed to IR.

Results: Herein, we found that IR increased infarct volume and pathological damage to the cerebral cortex after global cerebral artery occlusion/reperfusion. In addition, miR-374a-5p gene expression decreased, while MAPK6, NLRP3, and smad6 protein expressions increased in the IR group. TNF-α and IL-1β protein levels increased in the ischemic cortex. Treatment with NAC significantly attenuated infarct size, inflammation and reversed aforementioned molecule levels.

Conclusion: Taken together, these results suggested that ischemic insult can increase infarct size, neuronal damage, and inflammation may in part by modulating miR-374a-5p, MAPK6, NLRP3, and smad6 pathway in the brain cortex after cerebral IR insult and providing new clues to molecular mechanisms and treatment targets in IS. It can be alleviated by NAC as a potential therapy for someone afflicted with ischemia.

First Name
 
Last Name
 
Email Address
 
Comments
 
Security code


Abstract View: 28

Your browser does not support the canvas element.


PDF Download: 61

Your browser does not support the canvas element.

Submitted: 27 May 2024
Accepted: 24 Aug 2024
ePublished: 17 Sep 2024
EndNote EndNote

(Enw Format - Win & Mac)

BibTeX BibTeX

(Bib Format - Win & Mac)

Bookends Bookends

(Ris Format - Mac only)

EasyBib EasyBib

(Ris Format - Win & Mac)

Medlars Medlars

(Txt Format - Win & Mac)

Mendeley Web Mendeley Web
Mendeley Mendeley

(Ris Format - Win & Mac)

Papers Papers

(Ris Format - Win & Mac)

ProCite ProCite

(Ris Format - Win & Mac)

Reference Manager Reference Manager

(Ris Format - Win only)

Refworks Refworks

(Refworks Format - Win & Mac)

Zotero Zotero

(Ris Format - Firefox Plugin)