In this paper the concept of an ordered weighted average (OWA) operator is extended to any complete lattice endowed with a t-norm and a t-conorm. In the case of a complete distributive lattice it is ...shown to agree with a particular case of the discrete Sugeno integral. As an application, we show several ways of aggregating closed intervals by using OWA operators. In a complementary way, the notion of generalized Atanassov's operators is weakened in order to be extended to intervals contained in any lattice. This new approach allows us to build a kind of binary aggregation functions for complete lattices, including OWA operators.
Stroke is a very common disease being the leading cause of death and disability worldwide. The immune response subsequent to an ischemic stroke is a crucial factor in its physiopathology and outcome. ...This response is not limited to the injury site. In fact, the immune response to the ischemic process mobilizes mainly circulating cells which upon activation will be recruited to the injury site. When a stroke occurs, molecules that are usually retained inside the cell bodies are released into the extracellular space by uncontrolled cell death. These molecules can bind to the Toll-like receptor 4 (TLR4) in circulating immune cells which are then activated, eliciting, although not exclusively, the inflammatory response to the stroke. In this review, we present an up-to-date summary of the role of the different peripheral immune cells in stroke as well as the role of TLR4 in the function of each cell type in ischemia. Also, we summarize the different antagonists developed against TLR4 and their potential as a pharmacological tool for stroke treatment.
Stroke is a devastating disease with an increasing prevalence. Part of the current development in stroke therapy is focused in the chronic phase, where neurorepair mechanisms such as neurogenesis, ...are involved. In the adult brain, one of the regions where neurogenesis takes place is the subventricular zone (SVZ) of the lateral ventricles. Given the possibility to develop pharmacological therapies to stimulate this process, we have performed a longitudinal analysis of neurogenesis in a model of cortical ischemia in mice. Our results show an initial decrease of SVZ proliferation at 24 h, followed by a recovery leading to an increase at 14d and a second decrease 28d after stroke. Coinciding with the 24 h proliferation decrease, an increase in the eutopic neuroblast migration towards the olfactory bulb was observed. The analysis of the neuroblast ectopic migration from the SVZ toward the lesion showed an increase in this process from day 14 after the insult. Finally, our data revealed an increased number of new cortical neurons in the peri-infarct cortex 65d after the insult. In summary, we report here critical check-points about post-stroke neurogenesis after cortical infarcts, important for the pharmacological modulation of this process in stroke patients.
Being the second most common cause of death in the industrial countries and one of the major causes of death and disability, stroke has a great effect on public health and is the neurological disease ...which accounts for the largest number of hospitalizations. In order to develop new treatments, biochemical mechanisms involved in brain damage have been investigated. Among them, oxidant species generated during stroke have been implicated as critical mediators of neuronal injury in this condition, although neuroprotective roles have also been demonstrated.
This review is focused on the role of the mitochondrial respiratory chain as both source and target of reactive oxygen and nitrogen species such as nitric oxide, superoxide and peroxynitrite produced in cerebral ischemia. The neuroprotective role of antioxidants or other molecules acting on the mitochondrial respiratory chain and ATP synthesis in the setting of cerebral ischemia is discussed.
Pretreatment with statins has been shown to reduce brain injury in cerebral ischemia. In this controlled randomized study, we investigated the influence of statin pretreatment and its withdrawal on ...the outcome of acute ischemic stroke patients.
From 215 patients admitted within 24 hours of a hemispheric ischemic stroke, 89 patients on chronic statin treatment were randomly assigned either to statin withdrawal for the first 3 days after admission (n = 46) or to immediately receive atorvastatin 20 mg/day (n = 43). The primary outcome event was death or dependency (modified Rankin Scale mRS score > 2) at 3 months. Early neurologic deterioration (END) and infarct volume at days 4 to 7 were secondary outcome variables. In a secondary analysis, outcome variables were compared with the nonrandomized patients without previous statin therapy (n = 126).
Patients with statin withdrawal showed a higher frequency of mRS score > 2 at the end of follow-up (60.0% vs 39.0%; p = 0.043), END (65.2% vs 20.9%; p < 0.0001), and greater infarct volume (74 45, 126 vs 26 12, 70 mL; p = 0.002) compared with the non-statin-withdrawal group. Statin withdrawal was associated with a 4.66 (1.46 to 14.91)-fold increase in the risk of death or dependency, a 8.67 (3.05 to 24.63)-fold increase in the risk of END, and an increase in mean infarct volume of 37.63 mL (SE 10.01; p < 0.001) after adjusting for age and baseline stroke severity. Compared with patients without previous treatment with statins, statin withdrawal was associated with a 19.01 (1.96 to 184.09)-fold increase in the risk of END and an increase in mean infarct volume of 43.51 mL (SE 21.91; p = 0.048).
Statin withdrawal is associated with increased risk of death or dependency at 90 days. Hence, this treatment should be continued in the acute phase of ischemic stroke.
Ordered Weighted Averaging (OWA) operators are a profusely applied class of averaging aggregation functions, i.e. operators that always yield a value between the minimum and the maximum of the ...inputs. The orness measure was introduced to classify the behavior of the OWA operators depending on the weight vectors. Defining a suitable orness measure is an arduous task when we deal with OWA operators defined over more intricate spaces, such us intervals or lattices. In this work we propose a suitable definition for the orness measure to classify OWA operators defined on the set of m-dimensional intervals taking real values in
. The orness measure is applied to decide which is the best partition of a continuous range that should be divided into four linguistic labels. This example shows the good behavior of the proposed orness measure.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Cannabinoids have emerged as brain protective agents under neurodegenerative conditions. Many neuroprotective actions of cannabinoids depend on the activation of specific receptors, ...cannabinoid receptor type 1 (CB1R) and type 2 (CB2R). The aim of the present study was to determine whether the CB2R and CB1R agonist WIN 55,212-2 (WIN) protects neonatal brain against focal cerebral ischemia-reperfusion and whether anti-inflammatory mechanisms play a role in protection. Seven-day-old rats were subjected to 90-min middle cerebral artery occlusion (MCAO), and injured rats were identified by diffusion-weighted MRI during the occlusion. After reperfusion, rats were subcutaneously administered 1 mg/kg of WIN or vehicle twice daily until sacrifice. MCAO led to increased mRNA expression of CB2R (but not CB1R), chemokine receptors (CCR2 and CX3CR1), and cytokines (IL-1β and TNFα), as well as increased protein expression of chemokines MCP-1 and MIP-1α and microglial activation 24 h after MCAO. WIN administration significantly reduced microglial activation at this point and attenuated infarct volume and microglial accumulation and proliferation in the injured cortex 72 h after MCAO. Cumulatively, our results show that the cannabinoid agonist WIN protects against neonatal focal stroke in part due to inhibitory effects on microglia.
Highlights • We identified HMGIY as a transcription factor (TF) regulated in brain ischemia. • Several genes implicated in angiogenesis share HMGIY TF binding sites. • Cerebral ischemia promotes ...changes in HMGIY gene expression. • Brain HMGIY interaction profile with other TFs changes under ischemic conditions. • HMGIY regulates VEGF and ANGPT-1 expression and promotes endothelial cell viability.
This paper provides a generalization of known results about fuzzy finite state machines, fuzzy transformation semigroups and their relationship by broading the truth values domain from the interval ...0,1 to a complete lattice endowed with a t-norm and a t-conorm. So, we deal with the concepts of L-fuzzy finite state machines and L-fuzzy transformation semigroups and we prove that the cited generalization is possible if and only if the t-norm and the t-conorm satisfy a distributive property. If we consider the complete lattice of the closed intervals inside the original lattice L, we give methods to obtain an interval lattice-valued finite state machine and an interval lattice-valued transformation semigroup from two L-fuzzy finite state machines or two L-fuzzy transformation semigroups, respectively. Conversely, we show two different ways to build a faithful L-fuzzy transformation semigroup from an interval lattice-valued state machine. In fact, both methods give the same result.
Abstract Chronic impairment of forelimb and digit movement is a common problem after stroke that is resistant to therapy. Although in the last years some studies have been performed to increase the ...efficacy of rehabilitative experience and training, the pharmacological approaches in this context remain poorly developed. We decided to study the effect of a chronic treatment with CDP-choline, a safe and well-tolerated drug that is known to stabilize membranes, on functional outcome and neuromorphological changes after stroke. To assess the functional recovery we have performed the staircase reaching test and the elevated body swing test (EBST), for studying sensorimotor integration and asymmetrical motor function respectively. The treatment with CDP-choline, initiated 24 h after the middle cerebral artery occlusion (MCAO) and maintained during 28 days, improved the functional outcome in both the staircase test (MCAO + CDP = 87.0 ± 6.6% pellets eaten vs. MCAO + SAL = 40.0 ± 4.5%; p < 0.05) and the EBST (MCAO + CDP = 70.0 ± 6.8% vs. MCAO + SAL = 88.0 ± 5.4%; contralateral swing p < 0.05). In addition, to study potential neuronal substrates of the improved function, we examined the dendritic morphology of layer V pyramidal cells in the undamaged motor cortex using a Golgi–Cox procedure. The animals treated with CDP-choline showed enhanced dendritic complexity and spine density compared with saline group. Our results suggest that a chronic treatment with CDP-choline initiated 24 h after the insult is able to increase the neuronal plasticity within noninjured and functionally connected brain regions as well as to promote functional recovery.
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