PMID- 32557772 OWN - NLM STAT- MEDLINE DCOM- 20210917 LR - 20210917 IS - 1097-4547 (Electronic) IS - 0360-4012 (Linking) VI - 98 IP - 10 DP - 2020 Oct TI - Direct arterial damage and neurovascular unit disruption by mechanical thrombectomy in a rat stroke model. PG - 2018-2026 LID - 10.1002/jnr.24671 [doi] AB - Mechanical thrombectomy (MT) is a standard treatment for acute ischemic stroke that could cause hemorrhagic complications. We aimed to evaluate the pathology of MT-induced arterial damage and neurovascular unit (NVU) disruption in relation to tissue-type plasminogen activator (tPA) injection for acute ischemic stroke. We induced transient middle cerebral artery occlusion in male SHR/Izm rats for 2 hr. This was followed by reperfusion with/without tPA (3 mg/kg) and "rough suture" insertion that mimicked MT once or thrice (MT1 or MT3). Compared with the control group, the tPA + MT3 group presented with an increase in the cerebral infarct and hemorrhage with severer IgG leakage. Moreover, structural damage reaching the tunica media was detected in the MT3 and tPA + MT3 groups. The tPA + MT3 group presented with increased matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression with some MMP9-positive cells expressing a neutrophil marker myeloperoxidase. Furthermore, basal lamina detachment from astrocyte foot processes was observed in the tPA + MT1 and tPA + MT3 groups. These findings suggest that MT causes direct arterial damage, as well as VEGF and MMP9 upregulation, which results in NVU disruption and hemorrhagic complications in acute ischemic stroke, especially when combined with tPA. CI - (c) 2020 Wiley Periodicals, Inc. FAU - Sasaki, Ryo AU - Sasaki R AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Yamashita, Toru AU - Yamashita T AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Tadokoro, Koh AU - Tadokoro K AUID- ORCID: 0000-0002-5049-0875 AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Matsumoto, Namiko AU - Matsumoto N AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Nomura, Emi AU - Nomura E AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Omote, Yoshio AU - Omote Y AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Takemoto, Mami AU - Takemoto M AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Hishikawa, Nozomi AU - Hishikawa N AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Ohta, Yasuyuki AU - Ohta Y AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Abe, Koji AU - Abe K AUID- ORCID: 0000-0003-1563-7226 AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200618 PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, rat) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 3.4.24.35 (Mmp9 protein, rat) SB - IM MH - Animals MH - Brain Ischemia/*etiology/metabolism/*pathology MH - Disease Models, Animal MH - Male MH - Matrix Metalloproteinase 9/metabolism MH - Neurovascular Coupling/*physiology MH - Rats MH - Rats, Inbred SHR MH - Stroke/*etiology/metabolism/*pathology MH - Thrombectomy/*adverse effects MH - Vascular Endothelial Growth Factor A/metabolism OTO - NOTNLM OT - RRID:AB_2146325 OT - RRID:AB_2212642 OT - RRID:AB_2827429 OT - RRID:AB_776512 OT - RRID:AB_94844 OT - hemorrhagic complication OT - ischemic stroke OT - mechanical thrombectomy OT - neurovascular unit OT - tPA EDAT- 2020/06/20 06:00 MHDA- 2021/09/18 06:00 CRDT- 2020/06/20 06:00 PHST- 2020/02/12 00:00 [received] PHST- 2020/04/11 00:00 [revised] PHST- 2020/05/19 00:00 [accepted] PHST- 2020/06/20 06:00 [pubmed] PHST- 2021/09/18 06:00 [medline] PHST- 2020/06/20 06:00 [entrez] AID - 10.1002/jnr.24671 [doi] PST - ppublish SO - J Neurosci Res. 2020 Oct;98(10):2018-2026. doi: 10.1002/jnr.24671. Epub 2020 Jun 18.