Protection of the brain following cerebral ischemia through the attenuation of PARP-1-induced neurovascular unit damage in rats

Zhang, Ruixue; Tang, Shi; Huang, Weiwei; Liu, Xiaomin; Li, Guohua; Chi, Heng; Zhu, Mingqing; Tang, Jinjin

doi:10.1016/j.brainres.2015.07.023

Cited by 19 publications

(13 citation statements)

References 31 publications

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“…In addition, we describe that a single or combined therapy of hypothermia and TES448 is insufficient in female rats to enhance histological recovery. Our data are in general agreement that PARP-1 levels are modified following ischemic injury in young and older animals [9, 11, 24] . It has been reported that different types of PARP inhibitors or a disruption of the gene were able to promote significant recovery in ischemic brain injury supporting the hypothesis that brain injury in the immature brain depends on PARP-1 activation [17–20].…”

Section: Discussionsupporting

confidence: 87%

“…Studies have provided evidence that molecular mechanisms in response to activation of PARP after experimental stroke are not identical in males and females probably explaining selectivity of PARP inhibitors [27]. It has been proposed that PARP-1-inhibitors are able to interact with all cell types of the neurovascular unit including the blood-brain barrier and to provide a better outcome compared to other neuroprotective strategies so far tested [9]. Therefore, we analyzed different cell types following HI and provide evidence that the cellular response after PARP-1 inhibition is diverse compared to the adult brain.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Poly(ADP-Ribose) Polymerase-1 Inhibition in a Neonatal Rodent Model of Hypoxic-Ischemic Injury

Klöfers

Kohaut

Bendix

et al. 2017

BioMed Research International

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Background Hypoxia ischemia (HI) to the developing brain occurs in 1–6 in 1000 live births. Large numbers of survivors have neurological long-term sequelae. However, mechanisms of recovery after HI are not understood and preventive measures or clinical treatments are not effective. Poly(ADP-ribose) polymerase-1 is overactivated in response to ischemia. In neonatal mice HI activates PARP-1 but its role in perinatal brain injury remains uncertain. Objective Aim of this study was to explore the effect of TES448 (PARP-1-inhibitor) and hypothermia after an ischemic insult. Design and Methods 10-day-old Wistar rats underwent HI. TES448 was given 10 min, 3 hrs, and 6 hrs after hypoxia. Hypothermia was started 30 min after HI and brains were dissected at P12. Western blotting and histological staining were used to evaluate for degree of injury. Results Protein expression of PARP-1 levels was diminished after TES448 treatment. Cresyl violet and TUNEL staining revealed decreased injury in male rat pups following TES448 and combined treatment. Female rats showed increased numbers of TUNEL-positive cells after combined therapy. TES448 inhibited microglia activation after hypoxic-ischemic injury. A cellular response including NeuN, Olig2, and MBP was not affected by PARP-1-inhibition. Conclusions Inhibition of PARP-1 and hypothermia lead to an alteration of injury but this effect is sexually dimorphic.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Effects of Poly(ADP-Ribose) Polymerase-1 Inhibition in a Neonatal Rodent Model of Hypoxic-Ischemic Injury

Klöfers

Kohaut

Bendix

et al. 2017

BioMed Research International

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“…Cellular Physiology and Biochemistry of neurovascular units in ischemic brain injury [35,36]. In the present study, we found that OGD-induced PARP-1 increasing was inhibited by nuclear FKBP25 overexpression in endothelial cells.…”

Section: Cellular Physiology and Biochemistrysupporting

confidence: 53%

Elucidation of the FKBP25-60S Ribosomal Protein L7a Stress Response Signaling During Ischemic Injury

Jiang

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Peptidyl-prolyl cis-trans isomerase FKBP25 is a member of the FK506-binding proteins family which has peptidyl-prolyl cis/trans isomerase domain. The biological function and pathophysiologic role of FKBP25 remain elusive. Methods: The spatio-temporal changes in expression of endothelial FKBP25 upon oxygen-glucose deprivation (OGD) treatment were examined by Western blot and immunofluorescence. The immunoprecipitation and fluorescence resonance energy transfer (FRET) were used to address the interacting proteins with FKBP25. Results: In the present study, nuclear translocation of FKBP25 was observed following OGD in cultured endothelial cells. Intriguingly, FKBP25 nuclear translocation was further validated in peroxynitrite (ONOO^-)-treated endothelial cells. Coimmunoprecipitation and FRET data indicated that FKBP25 translocated into the nucleus, in which it interacted with 60S ribosomal protein L7a, while overexpression FKBP25 protect endothelial cells against OGD injury. Conclusion: Our findings reveal that the nuclear import of FKBP25 and binding with 60S ribosomal protein L7a are protective stress responses to ischemia/nitrosaive stress injury.

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“…Transmission electron microscopy (TEM) was carried out to visualize the BBB structural integrity as previously described [ 45 ]. Briefly, mice brain samples contain the bilateral parietal lobe sensorimotor cortex and the hippocampus were harvested under deep anesthesia and immediately sliced into 1mm 3 slabs, post-fixed in glutaraldehyde overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Potential implications of Apolipoprotein E in early brain injury after experimental subarachnoid hemorrhage: Involvement in the modulation of blood-brain barrier integrity

Pang

Peng

et al. 2016

Oncotarget

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Apolipoprotein E (Apoe) genetic polymorphisms have been implicated in the long term outcome of subarachnoid haemorrhage (SAH), but little is known about the effect of Apoe on the early brain injury (EBI) after SAH. This study investigated the potential role of APOE in EBI post-SAH. Multiple techniques were used to determine the early BBB disruption in EBI post-SAH in a murine model using wild-type (WT) and Apoe -/-(KO) mice. Progressive BBB disruption (Evans blue extravasation and T2 hyperintensity in magnetic resonance imaging) was observed before the peak of endogenous APOE expression elevation at 48h after SAH. Moreover, Apoe −/− mice exhibited more severe BBB disruption charcteristics after SAH than WT mice, including higher levels of Evans blue and IgG extravasation, T2 hyperintensity in magnetic resonance imaging, tight junction proteins degradation and endothelial cells death. Mechanistically, we found that APOE restores the BBB integrity in the acute stage after SAH via the cyclophilin A (CypA)-NF-κB-proinflammatory cytokines-MMP-9 signalling pathway. Consequently, although early BBB disruption causes neurological dysfunctions after SAH, we capture a different aspect of the effects of APOE on EBI after SAH that previous studies had overlooked and open up the idea of BBB disruption as a target of APOE-based therapy for EBI amelioration research in the future.

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Protection of the brain following cerebral ischemia through the attenuation of PARP-1-induced neurovascular unit damage in rats

Cited by 19 publications

References 31 publications

Effects of Poly(ADP-Ribose) Polymerase-1 Inhibition in a Neonatal Rodent Model of Hypoxic-Ischemic Injury

Effects of Poly(ADP-Ribose) Polymerase-1 Inhibition in a Neonatal Rodent Model of Hypoxic-Ischemic Injury

Elucidation of the FKBP25-60S Ribosomal Protein L7a Stress Response Signaling During Ischemic Injury

Potential implications of Apolipoprotein E in early brain injury after experimental subarachnoid hemorrhage: Involvement in the modulation of blood-brain barrier integrity

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