Hemopexin alleviates cognitive dysfunction after focal cerebral ischemia-reperfusion injury in rats.
Animals
Blood-Brain Barrier
/ drug effects
Brain Ischemia
/ drug therapy
Cognitive Dysfunction
/ prevention & control
Disease Models, Animal
Heme Oxygenase-1
/ metabolism
Hemopexin
/ administration & dosage
Male
Neuroprotective Agents
/ administration & dosage
Rats
Rats, Sprague-Dawley
Reperfusion Injury
/ drug therapy
Stroke
/ drug therapy
Blood-brain barrier
Cerebral ischemia-reperfusion injury
Heme-oxygenase-1
Hemopexin
Journal
BMC anesthesiology
ISSN: 1471-2253
Titre abrégé: BMC Anesthesiol
Pays: England
ID NLM: 100968535
Informations de publication
Date de publication:
15 01 2019
15 01 2019
Historique:
received:
01
10
2018
accepted:
04
01
2019
entrez:
17
1
2019
pubmed:
17
1
2019
medline:
24
1
2020
Statut:
epublish
Résumé
Ischemia-reperfusion (I/R) is a critical pathophysiological basis of cognitive dysfunction caused by ischemia stroke. Heme-oxygenase-1 (HO-1) is the rate-limiting enzyme for the elimination of excessive free heme by combining with hemopexin (HPX), a plasma protein that contributes to eliminating excessive free heme during ischemia stroke. This study aimed to elucidate whether HPX could alleviate cognitive dysfunction in rats subjected to cerebral I/R. Rats were randomly divided into five groups: sham, MCAO, Vehicle, HPX and HPX + protoporphyrin IX (ZnPPIX). Cerebral I/R was induced by MCAO. Saline, vehicle, HPX and HPX + ZnPPIX were injected intracerebroventricularly at the moment after reperfusion. Morris water maze (MWM) test was used to detect the learning and cognitive function. Western blot was used to detect the expression of HO-1 in ischemic penumbra. CD31/vWF double labeling immunofluorescence was used to detect the neovascularization in the penumbra hippocampus. The structure and function of blood-brain barrier (BBB) was detected by the permeability of Evans Blue (EB), water content of the brain tissue, the Ang1/Ang2 and VE-cadherin expression. Our study verified that HPX improved the learning and memory capacity. Hemopexin up-regulated HO-1 protein expression, the average vessel density in the penumbra hippocampus and the VE- cadherin expression but decreased the permeability of EB, the water content of brain tissue and the ratio of Ang1/Ang2. The effects were reversed by ZnPPIX, an inhibitor of HO-1. HPX can maintain the integrity of the blood-brain barrier and alleviate cognitive dysfunction after cerebral I/R through the HO-1 pathway.
Sections du résumé
BACKGROUND
Ischemia-reperfusion (I/R) is a critical pathophysiological basis of cognitive dysfunction caused by ischemia stroke. Heme-oxygenase-1 (HO-1) is the rate-limiting enzyme for the elimination of excessive free heme by combining with hemopexin (HPX), a plasma protein that contributes to eliminating excessive free heme during ischemia stroke. This study aimed to elucidate whether HPX could alleviate cognitive dysfunction in rats subjected to cerebral I/R.
METHODS
Rats were randomly divided into five groups: sham, MCAO, Vehicle, HPX and HPX + protoporphyrin IX (ZnPPIX). Cerebral I/R was induced by MCAO. Saline, vehicle, HPX and HPX + ZnPPIX were injected intracerebroventricularly at the moment after reperfusion. Morris water maze (MWM) test was used to detect the learning and cognitive function. Western blot was used to detect the expression of HO-1 in ischemic penumbra. CD31/vWF double labeling immunofluorescence was used to detect the neovascularization in the penumbra hippocampus. The structure and function of blood-brain barrier (BBB) was detected by the permeability of Evans Blue (EB), water content of the brain tissue, the Ang1/Ang2 and VE-cadherin expression.
RESULTS
Our study verified that HPX improved the learning and memory capacity. Hemopexin up-regulated HO-1 protein expression, the average vessel density in the penumbra hippocampus and the VE- cadherin expression but decreased the permeability of EB, the water content of brain tissue and the ratio of Ang1/Ang2. The effects were reversed by ZnPPIX, an inhibitor of HO-1.
CONCLUSION
HPX can maintain the integrity of the blood-brain barrier and alleviate cognitive dysfunction after cerebral I/R through the HO-1 pathway.
Identifiants
pubmed: 30646866
doi: 10.1186/s12871-019-0681-2
pii: 10.1186/s12871-019-0681-2
pmc: PMC6334464
doi:
Substances chimiques
Neuroprotective Agents
0
Hemopexin
9013-71-2
Heme Oxygenase-1
EC 1.14.14.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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