Cortical spreading depolarization (CSD) induces pro-inflammatory gene expression in brain tissue. However, previous studies assessing the relationship between CSD and inflammation have used invasive methods that directly trigger inflammation. To eliminate the injury confounder, we induced CSDs non-invasively through intact skull using optogenetics in Thy1-channelrhodopsin-2 transgenic mice. We corroborated our findings by minimally invasive KCl-induced CSDs through thinned skull. Six CSDs induced over 1 h dramatically increased cortical interleukin-1β (IL-1β), chemokine (C-C motif) ligand 2 (CCL2), and tumor necrosis factor-α (TNF-α) mRNA expression peaking around 1, 2 and 4 h, respectively. Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were only modestly elevated. A single CSD also increased IL-1β, CCL2, and TNF-α, and revealed an ultra-early IL-1β response within 10 min. The response was blunted in IL-1 receptor-1 knockout mice, implicating IL-1β as an upstream mediator, and suppressed by dexamethasone, but not ibuprofen. CSD did not alter systemic inflammatory indices. In summary, this is the first report of pro-inflammatory gene expression after non-invasively induced CSDs. Altogether, our data provide novel insights into the role of CSD-induced neuroinflammation in migraine headache pathogenesis and have implications for the inflammatory processes in acute brain injury where numerous CSDs occur for days.

BACKGROUND AND PURPOSE: Combination of high-resolution C-arm CT and novel metal artifact reduction software may contribute to the assessment of aneurysms treated with stent-assisted coil embolization. This study aimed to evaluate the efficacy of a novel Metal Artifact Reduction prototype software combined with the currently available high spatial-resolution C-arm CT prototype implementation by using an experimental aneurysm model treated with stent-assisted coil embolization. MATERIALS AND METHODS: Eight experimental aneurysms were created in 6 swine. Coil embolization of each aneurysm was performed by using a stent-assisted technique. High-resolution C-arm CT with intra-arterial contrast injection was performed immediately after the treatment. The obtained images were processed with Metal Artifact Reduction. Five neurointerventional specialists reviewed the image quality before and after Metal Artifact Reduction. Observational and quantitative analyses (via image analysis software) were performed. RESULTS: Every aneurysm was successfully created and treated with stent-assisted coil embolization. Before Metal Artifact Reduction, coil loops protruding through the stent lumen were not visualized due to the prominent metal artifacts produced by the coils. These became visible after Metal Artifact Reduction processing. Contrast filling in the residual aneurysm was also visualized after Metal Artifact Reduction in every aneurysm. Both the observational (P < .0001) and quantitative (P < .001) analyses showed significant reduction of the metal artifacts after application of the Metal Artifact Reduction prototype software. CONCLUSIONS: The combination of high-resolution C-arm CT and Metal Artifact Reduction enables differentiation of the coil mass, stent, and contrast material on the same image by significantly reducing the metal artifacts produced by the platinum coils. This novel image technique may improve the assessment of aneurysms treated with stent-assisted coil embolization.

Recent works highlight the therapeutic potential of targeting cyclic guanosine monophosphate (cGMP)-dependent pathways in the context of brain ischemia/reperfusion injury (IRI). Although cGMP-dependent protein kinase I (cGKI) has emerged as a key mediator of the protective effects of nitric oxide (NO) and cGMP, the mechanisms by which cGKI attenuates IRI remain poorly understood. We used a novel, conditional cGKI knockout mouse model to study its role in cerebral IRI. We assessed neurological deficit, infarct volume, and cerebral perfusion in tamoxifen-inducible vascular smooth muscle cell-specific cGKI knockout mice and control animals. Stroke experiments revealed greater cerebral infarct volume in smooth muscle cell specific cGKI knockout mice (males: 96 ± 16 mm³; females: 93 ± 12 mm³, mean±SD) than in all control groups: wild type (males: 66 ± 19; females: 64 ± 14), cGKI control (males: 65 ± 18; females: 62 ± 14), cGKI control with tamoxifen (males: 70 ± 8; females: 68 ± 10). Our results identify, for the first time, a protective role of cGKI in vascular smooth muscle cells during ischemic stroke injury. Moreover, this protective effect of cGKI was found to be independent of gender and was mediated via improved reperfusion. These results suggest that cGKI in vascular smooth muscle cells should be targeted by therapies designed to protect brain tissue against ischemic stroke.

Background and Purpose: Intracranial aneurysm formation and rupture risk are, in part, determined by genetic factors and sex. To examine their role, we compared 3 mouse strains commonly used in cerebrovascular studies in a model of intracranial aneurysm formation and rupture. Methods: Intracranial aneurysms were induced in male CD1 (Crl:CD1[ICR]), male and female C57 (C57BL/6NCrl), and male 129Sv (129S2/SvPasCrl or 129S1/SvImJ) mice by stereotaxic injection of elastase at the skull base, combined with systemic deoxycorticosterone acetate–salt hypertension. Neurological deficits and mortality were recorded. Aneurysms and subarachnoid hemorrhage grades were quantified postmortem, either after spontaneous mortality or at 7 to 21 days if the animals survived. In separate cohorts, we examined proinflammatory mediators by quantitative reverse transcriptase–polymerase chain reaction, arterial blood pressure via the femoral artery, and the circle of Willis by intravascular latex casting. Results: We found striking differences in aneurysm formation, rupture, and postrupture survival rates among the groups. 129Sv mice showed the highest rates of aneurysm rupture (80%), followed by C57 female (36%), C57 male (27%), and CD1 (21%). The risk of aneurysm rupture and the presence of unruptured aneurysms significantly differed among all 3 strains, as well as between male and female C57. The same hierarchy was observed upon Kaplan-Meier analysis of both overall survival and deficit-free survival. Subarachnoid hemorrhage grades were also more severe in 129Sv. CD1 mice showed the highest resistance to aneurysm rupture and the mildest outcomes. Higher mean blood pressures and the major phenotypic difference in the circle of Willis anatomy in 129Sv provided an explanation for the higher incidence of and more severe aneurysm ruptures. TNFα (tumor necrosis factor-alpha), IL-1β (interleukin-1-beta), and CCL2 (chemokine C-C motif ligand 2) expressions did not differ among the groups. Conclusions: The outcome of elastase-induced intracranial aneurysm formation and rupture in mice depends on genetic background and shows sexual dimorphism.

Purpose: We aimed to evaluate the safety and feasibility of the distal transradial approach (DTRA) as a novel technique for cerebral angiography based on our institutional initial experience. Methods: We retrospectively analyzed our institutional database of consecutive diagnostic cerebral angiographies performed with DTRA from December 2018 to August 2019. Patient demographics and clinical and procedural data were recorded. Results: In total, 51 diagnostic cerebral angiographies in 51 patients (age, 15–83 years; mean age, 59.4 years, SD 13.5; 35 (69%) females) were performed or attempted with DTRA. Ultrasound evaluation showed that the mean inner distal radial artery diameter was significantly smaller than the mean inner forearm radial artery diameter (2.19 mm vs. 2.56 mm, P < 0.001). Cannulation via the distal radial artery was successful in 47 (92%) procedures. In the four procedures that failed, operators converted to the ipsilateral transradial approach without repositioning or redraping. Selective catheterization of the intended vessel was achieved in 64 (91%) of 70 vessels. In the remaining six, operators achieved the objective of the examination with angiography injecting from proximal and conversion to another approach was not required. One patient experienced temporary numbness around the puncture site after the procedure. No radial artery occlusion was identified in the patients who underwent ultrasound evaluation. Conclusion: Our results demonstrate that DTRA could become a standard approach for diagnostic cerebral angiography owing to the low complication rate and the high cannulation success rate.