PMID- 33287606
OWN - NLM
STAT- MEDLINE
DCOM- 20221024
LR  - 20221024
IS  - 1563-5279 (Electronic)
IS  - 0020-7454 (Linking)
VI  - 132
IP  - 11
DP  - 2022 Nov
TI  - Hydrogen sulfide attenuates hyperhomocysteinemia-induced blood-brain barrier 
      permeability by inhibiting MMP-9.
PG  - 1061-1071
LID - 10.1080/00207454.2020.1860967 [doi]
AB  - Backgroud: Hyperhomocysteinemia (HHcy) is implicated in various neurovascular 
      disorders including vascular dementia, subarachnoid hemorrhage and stroke. 
      Elevated homocysteine (Hcy) levels are associated with increased oxidative stress 
      and compromised blood-brain barrier (BBB) integrity. Hydrogen sulfide (H(2)S) has 
      recently emerged as potent neuroprotective molecule in various neurological 
      conditions including those associated with HHcy. The present study evaluates the 
      protective effect of sodium hydrogen sulfide (NaHS; a source of H(2)S) on 
      HHcy-induced BBB dysfunction and underpin molecular mechanisms.Materials and 
      methods: Supplementation of NaHS restored the increased BBB permeability in the 
      cortex and hippocampus of HHcy animals assessed in terms of diffused sodium 
      fluorescein and Evans blue tracer dyes in the brain. Activity of matrix 
      metalloproteinases (MMPs) assessed by gelatinase activity and in situ gelatinase 
      assay was restored to the normal in the cortex and hippocampus of HHcy animals 
      supplemented with NaHS.Results: Application of gelatin zymography revealed that 
      specifically MMP-9 activity was increased in the cortex and hippocampus of HHcy 
      animals, which was inhibited by NaHS supplementation. Real-time RT-PCR analysis 
      showed that NaHS administration also decreased mRNA expression of MMP-9 in the 
      hippocampus of HHcy animals. NaHS supplementation was further observed to reduce 
      water retention in the brain regions of Hcy treated animals.Conclusion: Taken 
      together, these findings suggest that NaHS supplementation ameliorates 
      HHcy-induced BBB permeability and brain edema by inhibiting the mRNA expression 
      and activity of MMP-9. Therefore, H(2)S and H(2)S releasing drugs may be used as 
      a novel therapeutic approach to treat HHcy-associated neurovascular disorders.
FAU - Kumar, Mohit
AU  - Kumar M
AD  - Department of Biochemistry, Basic Medical Science Block-II, Panjab University, 
      Chandigarh, India.
AD  - College of Pharmacy, University of Kentucky, Lexington, KY, USA.
FAU - Sandhir, Rajat
AU  - Sandhir R
AD  - Department of Biochemistry, Basic Medical Science Block-II, Panjab University, 
      Chandigarh, India.
LA  - eng
PT  - Journal Article
DEP - 20210201
PL  - England
TA  - Int J Neurosci
JT  - The International journal of neuroscience
JID - 0270707
RN  - YY9FVM7NSN (Hydrogen Sulfide)
RN  - FWU2KQ177W (sodium bisulfide)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - 45PG892GO1 (Evans Blue)
RN  - TPY09G7XIR (Fluorescein)
RN  - 9000-70-8 (Gelatin)
RN  - YGR27ZW0Y7 (sodium sulfide)
RN  - 0 (RNA, Messenger)
RN  - 9NEZ333N27 (Sodium)
RN  - 0 (Coloring Agents)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 059QF0KO0R (Water)
SB  - IM
MH  - Animals
MH  - *Hydrogen Sulfide/pharmacology/therapeutic use/metabolism
MH  - *Hyperhomocysteinemia/complications/drug therapy
MH  - Blood-Brain Barrier
MH  - Matrix Metalloproteinase 9/metabolism/pharmacology/therapeutic use
MH  - Evans Blue/metabolism/pharmacology/therapeutic use
MH  - Fluorescein/metabolism/pharmacology/therapeutic use
MH  - Gelatin/metabolism/pharmacology/therapeutic use
MH  - Permeability
MH  - RNA, Messenger/metabolism
MH  - Sodium
MH  - Coloring Agents/metabolism/pharmacology/therapeutic use
MH  - Homocysteine
MH  - Water/metabolism/pharmacology
OTO - NOTNLM
OT  - Blood brain barrier
OT  - brain edema
OT  - homocysteine
OT  - hydrogen sulfide
OT  - matrix metalloproteinase
EDAT- 2020/12/09 06:00
MHDA- 2022/10/25 06:00
CRDT- 2020/12/08 05:30
PHST- 2020/12/09 06:00 [pubmed]
PHST- 2022/10/25 06:00 [medline]
PHST- 2020/12/08 05:30 [entrez]
AID - 10.1080/00207454.2020.1860967 [doi]
PST - ppublish
SO  - Int J Neurosci. 2022 Nov;132(11):1061-1071. doi: 10.1080/00207454.2020.1860967. 
      Epub 2021 Feb 1.