Browsing by Subject "ischemic stroke"

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  • Muhammad, Sajjad; Chaudhry, Shafqat Rasul; Kahlert, Ulf Dietrich; Niemelä, Mika; Hänggi, Daniel (2021)
    Ischemic stroke is still among the leading causes of mortality and morbidity worldwide. Despite intensive advancements in medical sciences, the clinical options to treat ischemic stroke are limited to thrombectomy and thrombolysis using tissue plasminogen activator within a narrow time window after stroke. Current state of the art knowledge reveals the critical role of local and systemic inflammation after stroke that can be triggered by interactions taking place at the brain and immune system interface. Here, we discuss different cellular and molecular mechanisms through which brain-immune interactions can take place. Moreover, we discuss the evidence how the brain influence immune system through the release of brain derived antigens, damage-associated molecular patterns (DAMPs), cytokines, chemokines, upregulated adhesion molecules, through infiltration, activation and polarization of immune cells in the CNS. Furthermore, the emerging concept of stemness-induced cellular immunity in the context of neurodevelopment and brain disease, focusing on ischemic implications, is discussed. Finally, we discuss current evidence on brain-immune system interaction through the autonomic nervous system after ischemic stroke. All of these mechanisms represent potential pharmacological targets and promising future research directions for clinically relevant discoveries.
  • Campbell, Bruce C. V.; Mitchell, Peter J.; Churilov, Leonid; Keshtkaran, Mahsa; Hong, Keun-Sik; Kleinig, Timothy J.; Dewey, Helen M.; Yassi, Nawaf; Yan, Bernard; Dowling, Richard J.; Parsons, Mark W.; Wu, Teddy Y.; Brooks, Mark; Simpson, Marion A.; Miteff, Ferdinand; Levi, Christopher R.; Krause, Martin; Harrington, Timothy J.; Faulder, Kenneth C.; Steinfort, Brendan S.; Ang, Timothy; Scroop, Rebecca; Barber, P. Alan; McGuinness, Ben; Wijeratne, Tissa; Phan, Thanh G.; Chong, Winston; Chandra, Ronil V.; Bladin, Christopher F.; Rice, Henry; de Villiers, Laetitia; Ma, Henry; Desmond, Patricia M.; Meretoja, Atte; Cadilhac, Dominique A.; Donnan, Geoffrey A.; Davis, Stephen M.; EXTEND-IA Investigators (2017)
    Background: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. Methods: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014). Results: There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12-19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00-0.91) in the alteplase-only versus 0.91 (0.65-1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplaseonly group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2-8.7) versus 8.9 (4.7-13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2-13.1) versus 4.9 (0.3-8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3-11) days versus 8 (5-14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0-28) versus 27 (0-65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365. c Conclusion: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life.
  • Järvinen, Elli Katariina (Helsingin yliopisto, 2021)
    Ischemic stroke is a complex disease involving multiple pathophysiological mechanisms. To date, many therapeutic intervention strategies such as anti-inflammatory treatments have been tested, but none of them has been successful. Previous studies have shown that mesencephalic astrocyte-derived neurotrophic factor (MANF) improves stroke recovery and increases the expression of phagocytosis related genes. In this study, the phagocytic and inflammatory effect of monocyte chemoattractant protein 1 (MCP-1), macrophage colony-stimulating factor (M-CSF), complement component 3 (C3), adhesion G protein-coupled receptor E1 (ADGRE1), MER receptor tyrosine kinase (MerTK) and mesencephalic astrocyte-derived neurotrophic factor (MANF) on microglia were studied simultaneously for the first time. The phagocytosis related genes were transiently transfected into a microglial cell line and studied in vitro utilizing phagocytosis assay, fluorescence-activated cell sorting, Western blot and enzyme-linked immunosorbent assay. MCP-1, M-CSF and C3a were shown to enhance microglial phagocytosis without inducing a pro-inflammatory response. In addition, MerTK induces phagocytosis and the synthesis of pro-inflammatory cytokines. In conclusion, the real therapeutic potential of MCP-1, M-CSF, C3a and MerTK in stroke treatment should be further characterized and tested in vivo.
  • Saarela, Marika; Mustanoja, Satu; Pekkola, Johanna; Tyni, Tiina; Hernesniemi, Juha; Kivipelto, Leena; Tatlisumak, Turgut (2017)
    Background and purpose Moyamoya vasculopathy, a rare steno-occlusive progressive cerebrovascular disorder, has not been thoroughly studied in Caucasian populations. We established a registry of Finnish patients treated at the Helsinki University Hospital, to collect and report demographic and clinical data. Methods We collected data both retrospectively and prospectively from all the patients with a moyamoya vasculopathy referred to our hospital between January 1987 and December 2014. All patients underwent a neurological outpatient clinic visit. Results We diagnosed 61 patients (50 females, 10 children) with moyamoya vasculopathy. The mean age at the disease-onset was 31.517.9 years. The two most common presenting symptoms were ischemic stroke (n=31) and hemorrhage (n=8). Forty-four percent underwent revascularization surgery, and 70% were prescribed antithrombotic treatment. Conclusions The results support in part the Western phenotype of the disease considering the later presentation and larger female predominance compared to the Asian moyamoya vasculopathy reports. However, the proportion of ischemic strokes and hemorrhagic strokes is closer to Japanese population than German population. The absence of familial cases points to a different genetic profile in the Finnish patients.
  • Tolppanen, Heli (Helsingfors universitet, 2010)
    Ischemic stroke in young adults with patent foramen ovale (PFO) and/or atrial septal aneurysm is underinvestigated. Methods: We investigated 86 such patients (age 16-49 years) with long-term follow-up. Results: Most patients recovered well, one died and 15 retired prematurely due to the index stroke. Seven patients underwent PFO closure. Few stroke recurrences occurred (4%) either on aspirin or warfarin during the 6.5 years of follow-up. Conclusions: Our data suggest good outcome, low morbidity, and low recurrence. Finding the best secondary prevention measures requires randomized trials.
  • Haula, Tuuli-Maria; Puustinen, Juha; Takala, Mari; Holm, Anu (2020)
    Objectives Presence of sleep-disordered breathing (SDB) affects negatively recovery from stroke. The aim of this study is to evaluate the relationships between sleep-disordered breathing (SDB) and outcome measures in Finnish stroke unit cohort: mRS, need of rehabilitation and hospitalization time. Material and Methods An observational longitudinal study consisted of 95 patients referred to the Stroke Unit of Satakunta Hospital District over a period of November 2013 to March 2016. Patients were tested for SDB within 72 hr from the hospital admission because of ischemic stroke or TIA. The patients underwent polysomnography with NOX T3 wireless recorder. Results There are 37% (n = 35) non-OSA patients, 20% (n = 19) of patients have mild obstructive sleep apnea (OSA) and 39% (n = 37) have moderate/severe OSA and 4% (n = 4) have CSA. Patients with OSA have higher proportion of disability scores of mRS 3-5 (38%) compared to non-OSA (11%) and mild OSA (5%) patients on registration day (mRS0), and the same trend is seen at hospital discharge 35% versus 9% and 5%. (p = .009). Proportion of patients with OSA who needed rehabilitation is 65% (n = 19) versus non-OSA patients 17.5% (n = 4) and mild OSA patients 17.5% (n = 4;p = .039). We observed longer duration of hospitalization (5-15 days) in 29% of OSA patients compared to mild OSA patients 47% and OSA patients 54%. (p = .045). Conclusion Ischemic stroke patients with OSA have higher disability, higher need of rehabilitation, and longer hospitalization length. Prescreening tools for recognizing these stroke patients in acute phase could be valuable. That could result in earlier initiation of treatment and might prevent worse recovery from stroke.
  • NAVIGATE ESUS Investigators; Martinez-Majander, Nicolas; Ntaios, George; Liu, Yan Yun; Ylikotila, Pauli; Joensuu, Heikki; Saarinen, Jukka; Tiainen, Marjaana; Tatlisumak, Turgut (2020)
    Abstract Background Cancer is a frequent finding in ischemic stroke patients. We investigated the frequency of cancer among participants in NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban. Methods Trial participation required a recent embolic stroke of undetermined source (ESUS). Patients? history of cancer was recorded at time of study entry. During a mean follow-up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischemic stroke, major bleeding, and all-cause mortality were compared between patients with cancer and without cancer. Results Among 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban (254[7.0%] with cancer) and 3604 patients to aspirin (289[8.0%] with cancer). The annual rate of recurrent ischemic stroke was 4.5% in non-cancer patients in rivaroxaban arm and 4.6% in the aspirin arm (hazard ratio, HR 0.98 [95% CI 0.78-1.24]). In cancer patients, the rate of recurrent ischemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43 [95% CI 0.71-2.87]). Among cancer patients, the annual rate of major bleeds was nonsignificantly higher for rivaroxaban than aspirin (2.9% versus 1.1%; HR 2.57 [95% CI 0.67-9.96], P for interaction 0.95). All-cause mortality was similar in both groups. Conclusions Our exploratory analyses show that patients with ESUS and a history of cancer had similar rates of recurrent ischemic strokes and all-cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds.
  • Anttila, Jenni E.; Pöyhönen, Suvi; Airavaara, Mikko (2019)
    A stroke affecting the somatosensory pathway can trigger central post-stroke pain syndrome (CPSP). The symptoms often include hyperalgesia, which has also been described in rodents after the direct damage of the thalamus. Previous studies have shown that hemorrhagic stroke or ischemia caused by vasoconstriction in the thalamus induces increased pain sensitivity. We investigated whether inducing secondary damage in the thalamus by a cortical stroke causes similar pain hypersensitivity as has previously been reported with direct ischemic injury. We induced a focal cortical ischemia-reperfusion injury in male rats, quantified the amount of secondary neurodegeneration in the thalamus, and measured whether the thalamic neurodegeneration is associated with thermal or mechanical hypersensitivity. After one month, we observed extensive neuronal degeneration and found approximately 40% decrease in the number of NeuN+ cells in the ipsilateral thalamus. At the same time, there was a massive accumulation-a 30-fold increase-of phagocytic cells in the ipsilateral thalamus. However, despite the evident damage in the thalamus, we did not observe thermal or mechanical sensitization. Thus, thalamic neurodegeneration after cortical ischemia-reperfusion does not induce CPSP-like symptoms in rats, and these results suggest that direct ischemic damage is needed for CPSP induction. Despite not observing hyperalgesia, we investigated whether administration of cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) into the ipsilateral thalamus would reduce the secondary damage. We gave a single injection (10 mu g) of recombinant CDNF or MANF protein into the thalamus at 7 days post-stroke. Both CDNF and MANF treatment promoted the functional recovery but had no effect on the neuronal loss or the amount of phagocytic cells in the thalamus.