PMID- 38472651
OWN - NLM
STAT- Publisher
LR  - 20240313
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
DP  - 2024 Mar 12
TI  - Involvement of Calpain in Neurovascular Unit Damage through Up-regulating 
      PARP-NF-kappaB Signaling during Experimental Ischemic Stroke.
LID - 10.1007/s12035-024-04092-w [doi]
AB  - Calpain and PARP-NF-kappaB signaling are reported to participate in the ischemic 
      brain injury. In this study, it was investigated whether calpain was contributed 
      to the neurovascular unit (NVU) damage through up-regulating PARP-NF-kappaB signaling 
      during experimental ischemic stroke. Male Sprague-Dawley rats were suffered from 
      90 min of middle cerebral artery occlusion, followed by reperfusion. The NVU 
      damage was evaluated by the permeability of blood-brain barrier (BBB), the 
      degradation of proteins in extracellular matrix and tight junctions, and 
      ultrastructural changes. The inflammatory response was determined by the 
      expression of inflammatory genes driven by PARP-NF-kappaB signaling and the 
      activities of myeloperoxidase (MPO). Treatment with MDL 28,170, a calpain 
      inhibitor, improved neurological functions, reduced TUNEL staining index, 
      lessened brain swelling, and decreased infarct volume in ischemic rats. Moreover, 
      it reduced the BBB permeability, enhanced the levels of laminin, collagen IV and 
      occludin, and attenuated the ultrastructural damage of NVU in penumbra and core 
      after induction of ischemia. Meanwhile, it enhanced the levels of cytosolic IkappaBalpha, 
      lessened the levels of nuclear PARP and NF-kappaB p65, reduced the levels of ICAM-1, 
      TNF-alpha, IL-1beta, MMP-9, and MMP-2,and suppressed the activities of MPO in penumbra 
      and core. These data showed that calpain inhibition suppressed PARP-NF-kappaB 
      signaling-mediated inflammatory response, reduced NVU damage, and protected brain 
      against ischemic stroke, suggesting the involvement of calpain in the NVU damage 
      through up-regulating PARP-NF-kappaB signaling during brain ischemia.
CI  - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Yan, Wenhao
AU  - Yan W
AD  - Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, 450052, China.
FAU - Wang, Chunyang
AU  - Wang C
AD  - Department of Neuropharmacology, Beijing Key Laboratory of Central Nervous System 
      Injury, Beijing Neurosurgical Institute, Capital Medical University, 119 South 
      Fourth Ring West Road, Fengtai District, Beijing, 100070, China.
FAU - Zhao, Yumei
AU  - Zhao Y
AD  - Department of Neuropharmacology, Beijing Key Laboratory of Central Nervous System 
      Injury, Beijing Neurosurgical Institute, Capital Medical University, 119 South 
      Fourth Ring West Road, Fengtai District, Beijing, 100070, China.
FAU - Jiang, Yingying
AU  - Jiang Y
AD  - Department of Neuropharmacology, Beijing Key Laboratory of Central Nervous System 
      Injury, Beijing Neurosurgical Institute, Capital Medical University, 119 South 
      Fourth Ring West Road, Fengtai District, Beijing, 100070, China.
FAU - Sun, Ming
AU  - Sun M
AUID- ORCID: 0000-0001-5772-7305
AD  - Department of Neuropharmacology, Beijing Key Laboratory of Central Nervous System 
      Injury, Beijing Neurosurgical Institute, Capital Medical University, 119 South 
      Fourth Ring West Road, Fengtai District, Beijing, 100070, China. 
      sunmingbni99@163.com.
LA  - eng
GR  - 81271285/Innovative Research Group Project of the National Natural Science 
      Foundation of China/
PT  - Journal Article
DEP - 20240312
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
SB  - IM
OTO - NOTNLM
OT  - Calpain
OT  - Experimental ischemic stroke
OT  - Inflammatory response
OT  - Neurovascular unit
OT  - Nuclear factor kappa B
OT  - Poly(ADP-ribose) polymerases
EDAT- 2024/03/13 06:46
MHDA- 2024/03/13 06:46
CRDT- 2024/03/13 01:11
PHST- 2023/09/25 00:00 [received]
PHST- 2024/03/03 00:00 [accepted]
PHST- 2024/03/13 06:46 [medline]
PHST- 2024/03/13 06:46 [pubmed]
PHST- 2024/03/13 01:11 [entrez]
AID - 10.1007/s12035-024-04092-w [pii]
AID - 10.1007/s12035-024-04092-w [doi]
PST - aheadofprint
SO  - Mol Neurobiol. 2024 Mar 12. doi: 10.1007/s12035-024-04092-w.