Repair Mechanisms of the Neurovascular Unit after Ischemic Stroke with a Focus on VEGF

Moon, Sunhong; Chang, Mi-Sook; Koh, Seong‐Ho; Choi, Yoon Kyung

doi:10.3390/ijms22168543

Cited by 59 publications

(44 citation statements)

References 167 publications

(274 reference statements)

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“…The HO-1/CO-Nampt-SIRT1 pathway increases vascular endothelial growth factor secretion from astrocytes [ 20 ]. This finding demonstrates facilitated signaling for angiogenesis, neurogenesis, and vascular homeostasis [ 33 , 34 , 35 ]. Taken together, as a putative therapeutic agent, KRGE may enhance neurovascular regeneration after TBI by mediating astrocytic mitochondria activity through HO-1-Tom20.…”

Section: Discussionmentioning

confidence: 99%

Dual Effects of Korean Red Ginseng on Astrocytes and Neural Stem Cells in Traumatic Brain Injury: The HO-1–Tom20 Axis as a Putative Target for Mitochondrial Function

Kim

Moon

Jeon

et al. 2022

Cells

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Astrocytes display regenerative potential in pathophysiologic conditions. In our previous study, heme oxygenase-1 (HO-1) promoted astrocytic mitochondrial functions in mice via the peroxisome-proliferator-activating receptor-γ coactivator-1α (PGC-1α) pathway on administering Korean red ginseng extract (KRGE) after traumatic brain injury (TBI). In this study, KRGE promoted astrocytic mitochondrial functions, assessed with oxygen consumption and adenosine triphosphate (ATP) production, which could be regulated by the translocase of the outer membrane of mitochondria 20 (Tom20) pathway with a PGC-1α-independent pathway. The HO-1–Tom20 axis induced an increase in mitochondrial functions, detected with cytochrome c oxidase subunit 2 and cytochrome c. HO-1 crosstalk with nicotinamide phosphoribosyltransferase was concomitant with the upregulated nicotinamide adenine dinucleotide (NAD)/NADH ratio, thereby upregulating NAD-dependent class I sirtuins. In adult neural stem cells (NSCs), KRGE-treated, astrocyte-conditioned media increased oxygen consumption and Tom20 levels through astrocyte-derived HO-1. HO inactivation by Sn(IV) protoporphyrin IX dichloride in TBI mice administered KRGE decreased neuronal markers, together with Tom20. Thus, astrocytic HO-1 induced astrocytic mitochondrial functions. HO-1-related, astrocyte-derived factors may also induce neuronal differentiation and mitochondrial functions of adult NSCs after TBI. KRGE-mediated astrocytic HO-1 induction may have a key role in repairing neurovascular function post-TBI in peri-injured regions by boosting astrocytic and NSC mitochondrial functions.

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Section: Discussionmentioning

confidence: 99%

Dual Effects of Korean Red Ginseng on Astrocytes and Neural Stem Cells in Traumatic Brain Injury: The HO-1–Tom20 Axis as a Putative Target for Mitochondrial Function

Kim

Moon

Jeon

et al. 2022

Cells

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“…Secondly, the transplanted stem cells alter the injured environment via the cytokines secreted. The secreted cytokines might possess the effects of neuroprotection [ 12 , 39 , 40 , 41 ], neuroregeneration [ 42 , 43 ], angiogenesis [ 12 , 41 , 42 , 43 , 44 ], or immunomodulation [ 39 , 45 , 46 , 47 ], and thereby repair the damaged tissues or prevent them from further deterioration. From the RT-PCR results of our study, it is suggested that HUMSCs did not directly differentiate into neurons or astrocytes after transplantation into the infarcted cortex of the chronic stroke rats.…”

Section: Discussionmentioning

confidence: 99%

Xenograft of Human Umbilical Mesenchymal Stem Cells Promotes Recovery from Chronic Ischemic Stroke in Rats

Yeh

Chu

et al. 2022

IJMS

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Stroke is a leading cause of adult disability. In our previous study, transplantation of human umbilical mesenchymal stem cells (HUMSCs) in Wharton’s jelly in the acute phase of ischemic stroke promotes recovery in rats. Unfortunately, there is no cure for chronic stroke. Patients with chronic stroke can only be treated with rehabilitation or supportive interventions. This study aimed to investigate the potential of xenograft of HUMSCs for treating chronic stroke in rats. Rats were subjected to 90 min middle cerebral artery occlusion and then reperfusion to mimic ischemic cerebral stroke. On day 14 following stroke, HUMSCs were transplanted into the damaged cerebral cortex. The motor function in rats of the Stroke + HUMSCs group exhibited significant improvement compared to that of the Stroke + Saline group, and the trend persisted until day 56 post stroke. The cerebral cortex changes were tracked using magnetic resonance imaging, showing that cerebral atrophy was found starting on day 7 and was reduced significantly in rats receiving HUMSCs compared to that in the Stroke + Saline group from day 21 to day 56. HUMSCs were found to be existed in the rats’ cerebral cortex on day 56, with signs of migration. The grafted HUMSCs did not differentiate into neurons or astrocytes and may release cytokines to improve neuroprotection, decrease inflammation and increase angiogenesis. Our results demonstrate that xeno-transplantation of HUMSCs has therapeutic benefits for chronic ischemic stroke. Most importantly, patients do not need to use their own HUMSCs, which is a gospel thing for clinical patients.

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“…It was shown that in rats the systemic administration of MSCs promoted BBB stabilization due to the reduction of BBB leakage and enhancement of microvascular repair [ 65 ]. MSCs transplantation can decrease the expression of IL-1b, IL-6, and TNF-a, and upregulate the tight junction proteins ZO-1 and Claudin-5, thus contributing to the reduction of the BBB permeability in rat stroke model [ 66 ]. Huang et al demonstrated that MSCs induced decline of the tight junction proteins degradation, as well as increased expression of CD31 and pericyte density in the NVU after intravenous administration to rats [ 67 ].…”

Section: Blood–brain Barrier In Stroke and Its Response To Msc Transplantationmentioning

confidence: 99%

Cell Therapy of Stroke: Do the Intra-Arterially Transplanted Mesenchymal Stem Cells Cross the Blood–Brain Barrier?

Yarygin

Namestnikova

Sukhinich

et al. 2021

Cells

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Animal model studies and first clinical trials have demonstrated the safety and efficacy of the mesenchymal stem cells’ (MSCs) transplantation in stroke. Intra-arterial (IA) administration looks especially promising, since it provides targeted cell delivery to the ischemic brain, is highly effective, and can be safe as long as the infusion is conducted appropriately. However, wider clinical application of the IA MSCs transplantation will only be possible after a better understanding of the mechanism of their therapeutic action is achieved. On the way to achieve this goal, the study of transplanted cells’ fate and their interactions with the blood–brain barrier (BBB) structures could be one of the key factors. In this review, we analyze the available data concerning one of the most important aspects of the transplanted MSCs’ action—the ability of cells to cross the blood–brain barrier (BBB) in vitro and in vivo after IA administration into animals with experimental stroke. The collected data show that some of the transplanted MSCs temporarily attach to the walls of the cerebral vessels and then return to the bloodstream or penetrate the BBB and either undergo homing in the perivascular space or penetrate deeper into the parenchyma. Transmigration across the BBB is not necessary for the induction of therapeutic effects, which can be incited through a paracrine mechanism even by cells located inside the blood vessels.

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Repair Mechanisms of the Neurovascular Unit after Ischemic Stroke with a Focus on VEGF

Cited by 59 publications

References 167 publications

Dual Effects of Korean Red Ginseng on Astrocytes and Neural Stem Cells in Traumatic Brain Injury: The HO-1–Tom20 Axis as a Putative Target for Mitochondrial Function

Dual Effects of Korean Red Ginseng on Astrocytes and Neural Stem Cells in Traumatic Brain Injury: The HO-1–Tom20 Axis as a Putative Target for Mitochondrial Function

Xenograft of Human Umbilical Mesenchymal Stem Cells Promotes Recovery from Chronic Ischemic Stroke in Rats

Cell Therapy of Stroke: Do the Intra-Arterially Transplanted Mesenchymal Stem Cells Cross the Blood–Brain Barrier?

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