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Cranial burr hole with erythropoietin administration induces reverse arteriogenesis from the enriched extracranium

Authors
Park, GH; Shin, HS; Choi, ES; Yoon, BS; Choi, MH; Lee, SJ; Lee, KE; Lee, JS; Hong, JM
Citation
Neurobiology of disease, 132. : 104538-104538, 2019
Journal Title
Neurobiology of disease
ISSN
0969-99611095-953X
Abstract
It is challenging to revitalize ischemic penumbra after an acute stroke with intracranial perfusion insufficiency. To evaluate whether cranial burr hole and erythropoietin (EPO) generate effective revascularization, we investigated the efficacy of the augmentation method for reverse arteriogenesis from the healthy extracranial milieu. An intracranial perfusion insufficiency was created through bilateral internal carotid artery ligation (bICAL) in Sprague-Dawley rats. We administered recombinant human EPO (5000U/kg) or saline intraperitoneally for 3days after bICAL. Mechanical barrier disruption (MBD) was performed through a cranial burr hole with small dural cracks in the right hemisphere. The ipsilateral hemisphere with MBD grossly showed vascular networks between the extra- and intra-cranial spaces 2weeks after the MBD procedure. It also showed significantly increased vessels in the intracranial vasculature adjacent to the MBD region (p=0.0006). The levels of pro-angiogenic and inflammatory factors with prominent markers of vessel permeability were also significantly increased (MBD-only vs. control: Tnf-alpha, p=0.0007: Vegf, p=0.0206). In the EPO-administered group, such elevations in inflammation were significantly mitigated (combined vs. MBD-only: Tnf-alpha, p=0.0008). The ipsilateral hemisphere with MBD-EPO (vs. MBD-only) showed significantly increased vessels (RECA-1, p=0.0182) and their maturation (RECA-1/alpha-SMA, p=0.0046), with upregulation of tumor growth factor-beta1 (Tgf-beta1, p=0.037) and matrix metalloproteinase-2 (Mmp-2, p=0.0488). These findings were completely blocked by minocycline (MIC) administration during in vivo (Tgf-beta1, p=0.0009: Mmp-2, p<0.0001) and in vitro experiments (tube formation, p<0.0001). Our data suggest that the MBD procedure (for angiogenic routes) and EPO administration (for an arteriogenic booster) are complimentary and can facilitate successfully "reverse arteriogenesis" in subjects with intracranial perfusion insufficiency.
Keywords
AngiogenesisArteriogenesisCranial burr holeErythropoietinIschemic stroke
MeSH terms
AdultAgedAnimalsCerebral Angiography / methodsCerebral Arteries / diagnostic imaging*Cerebral Arteries / drug effectsCerebral Revascularization / methods*Combined Modality Therapy / methodsCraniotomy / methods*Erythropoietin / administration & dosage*Human Umbilical Vein Endothelial CellsHumansMaleMiddle AgedMoyamoya Disease / diagnostic imaging*Moyamoya Disease / drug therapy*Prospective StudiesRandom AllocationRatsRats, Sprague-DawleyRetrospective StudiesSkull / blood supplySkull / diagnostic imagingSkull / drug effects
DOI
10.1016/j.nbd.2019.104538
PMID
31344491
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
최, 문희이, 성준이, 진수홍, 지만
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