Platelet derived growth factor (PDGF)-B plays a neuroprotective role in brain damages, including ischemic stroke. It has been suggested recently that PDGF receptor β (PDGFRβ) expressed in brain pericytes as well as in neurons and astrocytes may mediate the neuroprotective role of PDGF-B. The aims of this study were to elucidate the roles of PDGFRβ signaling in brain pericytes after ischemic stroke. In a rat middle cerebral artery occlusion (MCAO) model, PDGFRβ expression was induced specifically in the pericytes in peri-infarct areas and its level was gradually increased. PDGF-B induced marked phosphorylation of Akt in cultured brain pericytes. Consistently, PDGF-B was upregulated in endothelial cells in per-infarct areas and Akt was strongly phosphorylated in the PDGFRβ-expressing pericytes in periinfarct areas after MCAO. In the cultured pericytes, PDGF-B induced cell growth and anti-apoptotic responses through Akt. Furthermore, PDGF-B significantly increased the expression of nerve growth factor (NGF) and neurotrophin-3 (NT-3) through Akt in the pericytes. Thus, the PDGFRβ-Akt signaling in brain pericytes may play various important roles leading to neuroprotection after ischemic stroke.

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Pericytes are mural cells abundantly present in cerebral microvessels and play important roles, including the formation and maintenance of the blood-brain barrier. Nox4 is a major source of reactive oxygen species in cardiovascular cells and modulate cellular functions, particularly under pathological conditions. In the present study, we found that the expression of Nox4 was markedly induced in microvascular cells, including pericytes, in peri-infarct areas after middle cerebral artery occlusion stroke models in mice. The upregulation of Nox4 was greater in a permanent middle cerebral artery occlusion model compared with an ischemia/reperfusion transient middle cerebral artery occlusion model. We performed permanent middle cerebral artery occlusion on mice with Nox4 overexpression in pericytes (Tg-Nox4). Infarct volume was significantly greater with enhanced reactive oxygen species production and blood-brain barrier breakdown in peri-infarct areas in Tg-Nox4, compared with littermate controls. In cultured brain pericytes, Nox4 was significantly upregulated by hypoxia and was promptly downregulated by reoxygenation. Phosphorylation of NFkB and production of matrix metalloproteinase 9 were significantly increased in both cultured pericytes overexpressing Nox4 and in periinfarct areas in Tg-Nox4. Collectively, Nox4 is upregulated in pericytes in peri-infarct areas after acute brain ischemia and may enhance blood-brain barrier breakdown through activation of NFkB and matrix metalloproteinase 9, thereby causing enlargement of infarct volume.

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ObjectivesThis cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)–associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database.MethodsWe analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge.ResultsDOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039).ConclusionsThis nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies.

• The 4D-PACK enables good visualization of distal cerebral arteries in moyamoya disease. • The 4D-PACK enables direct visualization of leptomeningeal collateral vessels in moyamoya disease. • Vessel visualization by 4D-PACK can be useful in assessing cerebral hemodynamics.

Purpose To evaluate and compare the performance of acceleration-selective arterial spin labeling (AccASL) magnetic resonance (MR) angiography in the visualization of cerebral arteries and collateral vessels in patients with Moyamoya disease with that of time-of-flight (TOF) MR angiography, with digital subtraction angiography (DSA) as the reference standard. Materials and Methods Thirty-six cerebral hemispheres from 22 patients with Moyamoya disease underwent TOF and AccASL MR angiography and DSA. Qualitative evaluations included imaging of the terminal internal carotid artery (ICA), distal middle cerebral arteries (MCAs), Moyamoya vessels, and leptomeningeal anastomosis (LMA) collaterals with reference to DSA. Quantitative evaluations included assessment of contrast-to-noise ratio (CNR) and number of vessels in MCA branches. The linear mixed-effect model was used to compare the two methods. Results Mean scores for qualitative evaluation were significantly higher with AccASL angiography than with TOF angiography for imaging distal MCAs (3.9 ± 0.3 [standard deviation] vs 2.9 ± 1.1; P < .001), Moyamoya vessels (3.6 ± 0.6 vs 2.7 ± 0.9, P < .001), and LMA collaterals (3.8 ± 0.6 vs 1.8 ± 0.7, P < .001). Scores for steno-occlusive degree around the terminal ICAs were better with TOF angiography than with AccASL angiography (2.6 ± 0.5 vs 2.4 ± 0.6, P = .023). CNRs in the M4 segment were significantly higher with AccASL angiography (11.9 ± 12.9, P < .001) than with TOF angiography (4.1 ± 7.9). The number of vessels was significantly higher with AccASL angiography (18.3 ± 5.0, P < .001) than with TOF angiography (8.9 ± 4.9). The increase in the number of vessels from TOF angiography to AccASL angiography was greater in patients with severe ICA steno-occlusion (late ICA stage group, 11.4 ± 4.5; early ICA stage group, 6.8 ± 4.0; P = .007) and well-developed leptomeningeal anastomosis (mildly developed LMA group, 7.1 ± 4.3; well-developed LMA group, 11.3 ± 4.5; P = .011). Conclusion AccASL MR angiography enables better visualization of distal cerebral arteries and collateral vessels in patients with Moyamoya disease than does TOF MR angiography, while TOF MR angiography enables better visualization of stenosis of proximal arteries. Both methods work in a mutually beneficial manner in the assessment of cerebral arteries. RSNA, 2017 Online supplemental material is available for this article.