• Experimental stroke: ischaemic lesion volume and oedema formation differ among rat strains (a comparison between Wistar and Sprague-Dawley rats using MRI)

      Walberer, Maureen; Stolz, Erwin; Muller, Clemens; Friedrich, C.; Rottger, Carina; Blaes, F.; Kaps, Manfred; Fisher, Marc; Bachmann, Georg; Gerriets, Tibo (2006-02-08)
      Investigating focal cerebral ischaemia requires animal models that are relevant to human stroke. This study was designed to evaluate the influence of early reperfusion and choice of rat strains on infarct volume and oedema formation. Thirty-six Wistar and Sprague-Dawley rats were subjected to temporary middle cerebral artery occlusion (MCAO) for 90 min (groups I and II) or to permanent MCAO (groups III and IV) using the suture technique. Ischaemic lesion volume and oedema formation were quantified 24 h after MCAO using 7T-magnetic resonance imaging (MRI). Impact of rat strains: Reperfusion led to significant larger ischaemic lesion volumes in Wistar rats as compared to Sprague-Dawley rats (P<0.0005). Oedema formation was similar in both rat strains. Permanent MCAO led to significantly larger ischaemic lesion volumes in Sprague-Dawley rats (P<0.05). Oedema formation, however, was significantly more accentuated in Wistar rats (P<0.005). Impact of reperfusion: Reperfusion did not cause any changes in ischaemic lesion volume in Wistar rats. Oedema formation, however, was significantly reduced (P<0.0005). In Sprague-Dawley rats, reperfusion caused a significant reduction of ischaemic lesion volume (P<0.00005), but did not modify oedema formation. These findings emphasize the critical importance of rat strain differences in experimental stroke research.
    • Flow diverter implantation in a rat model of sidewall aneurysm: a feasibility study

      Aquarius, Rene; Smits, Debby; Gounis, Matthew J.; Leenders, William P.; de Vries, Joost (2017-02-08)
      BACKGROUND: More challenging animal models are needed to elucidate the efficacy of flow diverter (FD) designs and the mechanisms behind observed complications. The purpose of this study is to demonstrate the feasibility of implanting a FD in a sidewall aneurysm rat model. METHODS: An end-to-side anastomosis was created in the abdominal aorta of 36 rats using a decellularized donor pouch. A FD was subsequently implanted. RESULTS: After up to 3 months of follow-up, we observed that rats displayed normal growth and behavior. Mortality within the groups was low (2 rats, 5.6%). All aneurysms thrombosed after FD implantation and showed progressive soft tissue replacement of the thrombus during follow-up. The abdominal aortas remained patent. CONCLUSIONS: This model can be used to test the effects of FDs in future studies.
    • Long-term changes of functional MRI-based brain function, behavioral status, and histopathology after transient focal cerebral ischemia in rats

      Sicard, Kenneth M.; Henninger, Nils; Fisher, Marc; Duong, Timothy Q.; Ferris, Craig F. (2006-10-01)
      BACKGROUND AND PURPOSE: The relation between recovery of brain function and neurological status after clinical and experimental cerebral ischemia is incompletely characterized. We assessed the evolution of ischemic injury, behavioral status, and brain activity at acute to chronic periods after transient middle cerebral artery occlusion (tMCAO) in rats. METHODS: Male Sprague-Dawley rats were subjected to 20-minute tMCAO (n=10) or sham operation (n=10). Sensorimotor behavioral testing and multimodal (diffusion, perfusion, T2, and functional) MRI, as well as postmortem hematoxylin-eosin staining, were performed before and up to 21 days after tMCAO. MRI and histological parameters were evaluated in 5 regions of interest within the sensorimotor network. Diffusion, perfusion, and T2 lesion volumes were calculated according to previously established viability thresholds. RESULTS: Diffusion and perfusion lesions were present during occlusion but disappeared completely and permanently within 30 minutes after reperfusion, with no T2 lesions seen. Functional MRI and behavioral deficits did not normalize until 1 and 21 days after tMCAO, respectively. Histology demonstrated selective neuronal cell death at 7 and 21 days after reperfusion. CONCLUSIONS: Twenty-minute tMCAO produced distinct changes on multimodal MRI, histology, and behavioral parameters acutely and chronically. Normal findings on MRI after transient ischemia may not indicate normal tissue status, as behavioral and histological anomalies remain. Behavioral dysfunction persisting long after the recovery of MRI parameters may relate to the subtle neuronal damage seen on histology. Together, these results may help explain unremitting neurological deficits in stroke or transient ischemic attack patients with normal MRI findings.
    • ROCK inhibitor, Y-27632, reduces FBS-induced structural alteration in organ-cultured mesenteric artery

      Huh, Yang Hoon; Kweon, Hee-Seok; Kitazawa, Toshio (2013-10-24)
      Background Chronic treatment with fetal bovine serum (FBS) causes gradual vasoconstriction, vascular wall thickening, and contractility reduction in organ-cultured vascular tissues. We have previously demonstrated that Rho-associated kinase (ROCK) inhibitors prevent the functional alterations of small arteries in response to the FBS treatment. Here, we tested a further hypothesis that the chronic inhibition of ROCK has a protective effect on FBS-induced structural alterations. Methods To verify the new hypothesis, the rabbit mesenteric arterial rings were cultured in FBS-supplemented culture medium with or without Y-27632, a reversible ROCK inhibitor and then western blot, immunohistochemistry, apoptosis assay, and electron microscopy were performed using organ-cultured arterial rings. Results Chronic treatment with Y-27632 maintained the arterial diameter by preventing FBS-induced gradual arterial constriction during organ culture. Y-27632 also reduced the apoptosis and the loss of contractile myosin and actin filaments of smooth muscle cells. In addition, Y-27632 protected the morphological integrity between the endothelial cell layer and smooth muscle cell layer by preventing endothelial cell detachment and platelet endothelial cell adhesion molecule (PECAM) expression decrement. Conclusions Chronic ROCK inhibition provides protective effects against FBS-stimulated structural in addition to functional alterations of vascular smooth muscle cells and endothelial cells. These results strongly suggest that the RhoA/ROCK signaling is crucial for maintaining the structural and functional phenotypes of vasculature, and hence, chronic ROCK inhibition may provide protective effects on excessive growth factor-related vascular diseases including hypertension and atherosclerosis.
    • Spectacular shrinking deficit: insights from multimodal magnetic resonance imaging after embolic middle cerebral artery occlusion in Sprague-Dawley rats

      Henninger, Nils; Sicard, Kenneth M.; Fisher, Marc (2007-10-01)
      Almost no data is available on the serial changes in the brain after spectacular shrinking deficit (SSD) that may help understand this relatively rare clinical phenomenon. Quantitative diffusion-(DWI), perfusion-(PWI), T(1)-(T1WI), T(2)-weighted (T2WI), and functional magnetic resonance imaging (fMRI) were performed before, during, and up to 7 days after embolic middle cerebral artery occlusion (eMCAO) in male Sprague-Dawley rats (n=9). Region of interest (ROI) analysis was used to evaluate structural and functional MR signal changes within three ROIs defined by the apparent diffusion coefficient (ADC), cerebral blood flow (CBF) signatures, and final tissue viability. DWI, PWI, and T2WI lesion volumes were calculated using previously established viability thresholds and final infarct volumes ascertained with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Serial MRI demonstrated spontaneous reperfusion of initially hypoperfused MCA regions accompanied by substantial reduction of initial ADC and CBF lesions and gradual recovery of neurological outcome. Recovery rates of CBF/ADC abnormalities differed among ROIs. Functional magnetic resonance imaging showed persistent tissue dysfunction after the recovery of the CBF/ADC lesions. This study may facilitate our understanding of the pathophysiological mechanisms by which early, spontaneous reperfusion affects tissue fate and neurological function.
    • Treatment failure of fetal posterior communicating artery aneurysms with the pipeline embolization device

      Kan, Peter; Duckworth, Edward; Puri, Ajit S.; Velat, Greg; Wakhloo, Ajay K. (2015-09-11)
      Aneurysms that involve the internal carotid artery and posterior communicating artery junction and incorporate a fetal posterior cerebral artery are known as fetal posterior communicating artery aneurysms. We report the outcomes of four patients with fetal posterior communicating artery aneurysms who underwent treatment with the pipeline embolization device with or without adjunctive coil embolization. In our study, all four patients failed to achieve aneurysm occlusion at the last follow-up evaluation. Based on our results, we currently do not recommend the use of the flow diverter for the treatment of fetal posterior communicating artery aneurysms.
    • Two-year single-center experience with the 'Baby Trevo' stent retriever for mechanical thrombectomy in acute ischemic stroke

      Kuhn, Anna L.; Wakhloo, Ajay K.; Lozano, Juan Diego; Massari, Francesco; de Macedo Rodrigues, Katyucia; Marosfoi, Miklos G.; Perras, Mary; Brooks, Christopher; Howk, Mary; Rex, David E.; et al. (2017-06-01)
      OBJECTIVE: To evaluate the safety and efficacy of the 'Baby Trevo' (Trevo XP ProVue 3x20 mm Retriever) stent retriever for large vessel occlusions (LVOs) in acute ischemic stroke (AIS). MATERIALS AND METHODS: We retrospectively analyzed our stroke database and included all patients treated with the Baby Trevo for distal LVOs in AIS. Patient gender, mean age, vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) score at presentation, and modified Rankin Scale (mRS) score at baseline and 90-day follow-up were documented. Reperfusion rates for the vessels treated were recorded using the Thrombolysis in Cerebral Infarction (TICI) classification. Occurrence of vasospasm and new or evolving infarcts in the treated vascular territory was documented. RESULTS: Thirty-five subjects with a mean NIHSS score of 18 were included. The Baby Trevo device was used in 38 branches of the anterior and posterior circulations. TICI 2b/3 blood flow was restored after one single pass in 20/38 (52.6%) and after two or three passes in 11 vessels. The remaining vessels required either more than three passes, showed less than a TICI 2b/3 reperfusion (n=3), or demonstrated failure to retrieve the clot (n=4). TICI 2b/3 reperfusion was achieved in 30 patients (85.7%). No vessel injuries, rupture, or significant vasospasm were seen. Overall, a mRS score of CONCLUSIONS: Our preliminary data suggest that the 'Baby Trevo' achieves a high recanalization rate without any significant risk. Larger cohort studies are needed to validate the clinical benefit.