Insulin-Like Growth Factor-1 Is Neuroprotective in Aged Rats With Ischemic Stroke

Post-stroke systemic injections of insulin-like growth factor-1 (IGF-1) exert neuroprotective effects in rats. In the current study, we aimed to test the efficacy of IGF-1 neuroprotection in aged rats (24-25 months old) and to compare the results with adult rats (6-7 months old). Furthermore, we addressed putative differences in microglial responses to IGF-1 in adult and aged rats. Rats were subjected to ischemic stroke while they were conscious by infusing endothelin-1 (Et-1) through a guide cannula that was implemented in the vicinity of the middle cerebral artery (MCA). Rats were given subcutaneous injections of IGF-1 (1 mg/kg) at 30 min and 120 min after the insult. Post-stroke IGF-1 treatment reduced the infarct size by 34% and 38% in aged and adult rats, respectively. The IGF-1 treated adult rats also showed significant improvement in sensorimotor function following stroke, while this function was not significantly affected in aged rats. Furthermore, aged rats displayed exaggerated activation of microglia in the ischemic hemisphere. Significant reduction of microglial activation by IGF-1 was only detected at specific regions in the ipsilateral hemisphere of adult rats. We show that IGF-1 reduced infarct size in aged rats with an ischemic stroke. It remains to be established, however, whether the age-related changes in microglial function affect the improvement in behavioral outcomes

Neuroprotection by Insulin-like Growth Factor-1 in Rats with Ischemic Stroke is Associated with Microglial Changes and a Reduction in Neuroinflammation

We and others have shown that insulin-like growth factor-1 (IGF-1) is neuroprotective when administered systemically shortly following stroke. In the current study, we addressed the hypothesis that microglia mediate neuroprotection by IGF-1 following ischemic stroke. Furthermore, we investigated whether IGF-1 modulates pro- and anti-inflammatory mediators in ischemic brain with a special reference to microglia. Ischemic stroke was induced in normal conscious Wistar rats by infusing the vasoconstrictor, endothelin-1 (Et-1), next to middle cerebral artery (MCA). IGF-1 (300 μg) was injected subcutaneously (SC) at 30 and 120 min following stroke. Microglial inhibitor, minocycline, was injected intraperitoneally (IP) at 1 h before stroke (25 mg/kg) and 11 h after stroke (45 mg/kg). Post-stroke IGF-1 treatment reduced the infarct size and increased the sensorimotor function which coincided with an increase in the number of ameboid microglia in the ischemic cortex. Minocycline treatment abrogated the increase in ameboid microglia by IGF-1, while the effect of IGF-1 in the reduction of infarct size was only partially affected. IGF-1 suppressed mRNA expression of inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β in the ischemic hemisphere, while in purified microglia, only iNOS expression levels were reduced. Our findings show that microglia are a target for IGF-1 and that neuroprotection by IGF-1 coincides with down-regulation of inflammatory mediators which could be instrumental to the beneficial effects

Do design variations in the artificial disc influence cervical spine biomechanics? A finite element investigation

Various ball and socket-type designs of cervical artificial discs are in use or under investigation. Many artificial disc designs claim to restore the normal kinematics of the cervical spine. What differentiates one type of design from another design is currently not well understood. In this study, authors examined various clinically relevant parameters using a finite element model of C3–C7 cervical spine to study the effects of variations of ball and socket disc designs. Four variations of ball and socket-type artificial disc were placed at the C5–C6 level in an experimentally validated finite element model. Biomechanical effects of the shape (oval vs. spherical ball) and location (inferior vs. superior ball) were studied in detail. Range of motion, facet loading, implant stresses and capsule ligament strains were computed to investigate the influence of disc designs on resulting biomechanics. Motions at the implant level tended to increase following disc replacement. No major kinematic differences were observed among the disc designs tested. However, implant stresses were substantially higher in the spherical designs when compared to the oval designs. For both spherical and oval designs, the facet loads were lower for the designs with an inferior ball component. The capsule ligament strains were lower for the oval design with an inferior ball component. Overall, the oval design with an inferior ball component, produced motion, facet loads, implant stresses and capsule ligament strains closest to the intact spine, which may be key to long-term implant survival

Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria

The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs). This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from the appropriately chosen observed dynamics of a BRN. The discrete model can be further enriched by using the model checking tool HyTech along with delay parameters. This paves the way to accurately analyse a BRN and to make predictions about critical trajectories which lead to a normal or diseased response. In this paper, we apply the formal discrete and hybrid (discrete and continuous) modeling approaches to characterize behavior of the BRN associated with MyD88-adapter-like (MAL) – a key protein involved with innate immune response to infections. In order to demonstrate the practical effectiveness of our current work, different trajectories and corresponding conditions that may lead to the development of cerebral malaria (CM) are identified. Our results suggest that the system converges towards hyperinflammation if Bruton's tyrosine kinase (BTK) remains constitutively active along with pre-existing high cytokine levels which may play an important role in CM pathogenesis

The Degree of Applying Operations Management by the Peincipals of Public Secondary Schools in the Directorates of Euducation in Karak Governorate درجة تطبيق إدارة العمليات لدى مديري المدارس الثانوية الحكومية في مديريات محافظة الكرك

Abstract: he study aimed at finding out the degree of applying operations management by the principals of public secondary schools in the directorates of education in the Karak governorate from their point of view. The researchers used descriptive – survey methodology. The sample of the study consisted of (100) male and females principlals of these, (46) males and (54) were females. A questionnaire was developed as a study tool. It consisted of (5) fields and (56) items. The findings showed that the degree of applying operations management by the principals of public secondary schools was medium from their point of view. There were significant differences in the degree of applying operations management by publice secondary school principals in the directorates of education in Karak governorate attributed to sex variable, in favor of females, and to experience variable in favor of (10 years and above) category. The researchers recommended the need to train principals of public secondary schools in Karak governorate on method of process management. ملخص: هدفت الدراسة التعرف إلى درجة تطبيق إدارة العمليات لدى مديري المدارس الثانوية الحكومية في مديريات التربية والتعليم في محافظة الكرك من وجهة نظرهم. استخدم الباحثان المهنج الوصفي المسحي. بلغت عينة الدراسة (100) مديراً ومديرة, منهم (46) مدير و(54) مديرة. تم تطوير استبانة كأداة للدراسة مكونة من خمسة مجالات و(56) فقرة. أظهرت نتائج الدراسة أن درجة تطبيق إدارة العمليات لدى مديري المدارس الثانوية الحكومية في مديريات التربية والتعليم في محافظة الكرك من وجهة نظرهم جاءت متوسطة. ووجود فروق ذات دلالة إحصائية في درجة تطبيق إدارة العمليات لدى مديري المدارس الثانوية الحكومية في مديريات التربية والتعليم في محافظة الكرك تبعاً لمتغير الجنس ولصالح الإناث, وتبعاً لمتغير الخبرة ولصالح أصحاب ذوي الخبرة (10 سنوات فأكثر). وأوصى الباحثان ضرورة تدريب مديري المدارس الثانوية الحكومية في مديريات محافظة الكرك على أسلوب إدارة العمليات

Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets

Resolvin E1 (RvE1) is an omega-3 eicosapentaenoic acid (EPA)–derived lipid mediator generated during resolution of inflammation and in human vasculature via leukocyte-endothelial cell interactions. RvE1 possesses anti-inflammatory and proresolving actions. Here, we report that RvE1 in human whole blood rapidly regulates leukocyte expression of adhesion molecules. RvE1 in the 10- to 100-nM range stimulated L-selectin shedding, while reducing CD18 expression in both neutrophils and monocytes. When added to whole blood, RvE1 did not stimulate reactive oxygen species by either neutrophils or monocytes, nor did it directly stimulate cytokine/chemokine production in heparinized blood. Intravital microscopy (IVM) demonstrated that RvE1 rapidly reduced leukocyte rolling (∼ 40%) in venules of mice. In human platelet-rich plasma (PRP), RvE1 selectively blocked both ADP-stimulated and thromboxane receptor agonist U46619-stimulated platelet aggregation in a concentration-dependent manner. In contrast, Δ6,14-trans-RvE1 isomer was inactive. RvE1 did not block collagen-stimulated aggregation, and regulation of ADP-induced platelet aggregation was not further enhanced with aspirin treatment. These results indicate RvE1 is a potent modulator of leukocytes as well as selective platelet responses in blood and PRP, respectively. Moreover, the results demonstrate novel agonist-specific antiplatelet actions of RvE1 that are potent and may underlie some of the beneficial actions of EPA in humans