scholarly journals Secukinumab Attenuates Neuroinflammation and Neurobehavior Defect via PKCβ /ERK/NF-κB Pathway in a Rat Model of GMH

2021 ◽  
Author(s):  
Shengpeng Liu ◽  
Shuixiang Deng ◽  
Yan Ding ◽  
Jerry J. Flores ◽  
Xiaoli Zhang ◽  
...  
Keyword(s):  
Neurological Deficits ◽  
Clinical Event ◽  
Sprague Dawley ◽  
Neurological Outcomes ◽  
Beneficial Effects ◽  
Rat Pups ◽  
Tnf Α ◽  
Short And Long Term ◽  
Underlying Mechanisms

Abstract AimsGerminal matrix hemorrhage (GMH) is a disastrous clinical event for newborns. Neuroinflammation plays an important role in the development of neurological deficits after GMH. The purpose of this study is to investigate the anti-inflammatory role of secukinumab after GMH and its underlying mechanisms involving PKCβ/ERK/NF-κB signaling pathway.MethodsA total of 154 Sprague-Dawley P7 rat pups were used. GMH was induced by intraparenchymal injection of bacterial collagenase. Secukinumab was administered intranasally post-GMH. PKCβ activator PMA and p-ERK activator Ceramide C6 were administered intracerebroventricularly at 24h prior to GMH induction, respectively. Neurobehavioral tests, Western blot and immunohistochemistry were used to evaluate the efficacy of secukinumab in both short-term and long-term studies.ResultsEndogenous IL-17A, IL-17RA, PKCβ and p-ERK were increased after GMH. Secukinumab treatment improved short- and long-term neurological outcomes, reduced the expression of MPO and Iba-1 in the perihematoma area, and inhibited the expression of proinflammatory factors, such as NF-κB, IL-1β, TNF-α and IL-6. Additionally, PMA and ceramide C6 abolished the beneficial effects of secukinumab. ConclusionSecukinumab treatment suppressed neuroinflammation and attenuated neurological deficits after GMH, which was mediated through the downregulation of the PKCβ/ERK/NF-κB pathway. Secukinumab treatment may provide a promising therapeutic strategy for GMH patients.

scholarly journals CXCL-12 Attenuates Neuroinflammation via the CXCR4/PI3K/Akt Signaling Pathway in a Rat Model of SAH

2020 ◽  
Author(s):  
Gang Zuo ◽  
Ran Gu ◽  
Lu Wang ◽  
Cameron Lenahan ◽  
Hao Qu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Neuroprotective Effect ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Immunofluorescence Staining ◽  
Neurological Deficits ◽  
High Morbidity ◽  
Sprague Dawley ◽  
Short And Long Term

Abstract BackgroundSubarachnoid hemorrhage (SAH) is a cerebrovascular disease associated with high morbidity and mortality. CXCR4 provides a neuroprotective effect, which can alleviate brain injury and inflammation induced by stroke. The purpose of this study was to evaluate the anti-inflammatory effects and mechanisms of CXCR4 after SAH. Methods: SAH was induced via endovascular perforation. 185 male Sprague-Dawley rats were used. Recombinant human cysteine-X-cysteine chemokine ligand 12 (rh-CXCL-12) was administered intranasally at 1 h after SAH induction. To investigate the underlying mechanism, the inhibitors of CXCR4 and P13K, AMD3100 and LY294002, respectively, were administered intraperitoneally at 1 h before SAH. The short- and long-term neurobehavior were assessed, followed by performing western blot and immunofluorescence staining. ResultsWestern blotting suggested that the expressions of endogenous CXCL-12 and CXCR4 were increased, and peaked at 24 h following SAH. Immunofluorescence staining showed that CXCR4 was expressed on microglia. Rh-CXCL-12 treatment reduced the number of M1 macrophages and improved the short- and long-term neurological deficits after SAH. Meanwhile, rh-CXCL-12 treatment increased the levels of CXCL-12, CXCR4, PI3K, and p-Akt, and reduced the levels of IL-1β, IL-6, and TNF-α. Moreover, the administration of AMD3100 and LY294002 abolished the post-SAH neurobehavioral and neuroinflammatory improvements of CXCL-12 and its regulation of PI3K and p-Akt protein levels.ConclusionsThe CXCR4/PI3K/Akt signaling pathway may be involved in CXCL-12-mediated reduction of post-SAH neuroinflammation. Early administration of CXCL-12 may be a preventive and therapeutic strategy against delayed brain injury after SAH.

scholarly journals In vitro evidence for the involvement of H2S pathway in the effect of clodronate during inflammatory response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rosangela Montanaro ◽  
Alessio D’Addona ◽  
Andrea Izzo ◽  
Carlo Ruosi ◽  
Vincenzo Brancaleone
Keyword(s):  
Inflammatory Markers ◽  
In Vitro Study ◽  
Inos Expression ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Inflammatory Effect

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.

scholarly journals Perinatal neuroprotection update

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1939 ◽  
Author(s):  
Angie C. Jelin ◽  
Kirsten Salmeen ◽  
Dawn Gano ◽  
Irina Burd ◽  
Mari-Paule Thiet
Keyword(s):  
Preterm Delivery ◽  
Significant Risk ◽  
Autism Spectrum ◽  
Neurological Deficits ◽  
Delayed Cord Clamping ◽  
Neurological Outcomes ◽  
Cord Clamping ◽  
Cognitive Delay ◽  
Neurological Risk

Antepartum, intrapartum, and neonatal events can result in a spectrum of long-term neurological sequelae, including cerebral palsy, cognitive delay, schizophrenia, and autism spectrum disorders [1]. Advances in obstetrical and neonatal care have led to survival at earlier gestational ages and consequently increasing numbers of periviable infants who are at significant risk for long-term neurological deficits. Therefore, efforts to decrease and prevent cerebral insults attempt not only to decrease preterm delivery but also to improve neurological outcomes in infants delivered preterm. We recently published a comprehensive review addressing the impacts of magnesium sulfate, therapeutic hypothermia, delayed cord clamping, infections, and prevention of preterm delivery on the modification of neurological risk [2]. In this review, we will briefly provide updates to the aforementioned topics as well as an expansion on avoidance of toxin and infections, specifically the Zika virus.

scholarly journals Short- and long-term effects of various milk-delivery contingencies on sucking and nipple attachment in rat pups

1982 ◽  
Vol 15 (6) ◽  
pp. 543-556 ◽  
Author(s):  
Stephen C. Brake ◽  
Regina Sullivan ◽  
Sager D. Jayne ◽  
Myron Hofer
Keyword(s):  
Long Term Effects ◽  
Rat Pups ◽  
Short And Long Term

scholarly journals Active Infective Native and Prosthetic Valve Endocarditis: Short- and Long-Term Outcomes of Patients after Surgical Treatment

2021 ◽  
Vol 10 (9) ◽  
pp. 1868
Author(s):  
Mohamed Salem ◽  
Christine Friedrich ◽  
Mohammed Saad ◽  
Derk Frank ◽  
Mostafa Salem ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Prosthetic Valve ◽  
Pacemaker Implantation ◽  
Prosthetic Valve Endocarditis ◽  
Neurological Deficits ◽  
Preoperative Embolization ◽  
Duration Of Surgery ◽  
Cerebral Embolization ◽  
Short And Long Term

Background: Active infective endocarditis (IE) is a serious disease associated with high mortality. The current study represents our experience over 18 years with surgical treatment for active infective native and prosthetic valve endocarditis (INVE, IPVE). Method: Analysis of 413 patients (171 with IPVE vs. 242 with INVE) who underwent cardiac surgery due to IE between 2002 and 2020. Results: Patients with IPVE were significantly older (64.9 ± 13.2 years vs. 58.3 ± 15.5 years; p < 0.001) with higher EuroSCORE II (21.2 (12.7; 41.8) vs. 6.9 (3.0; 17.0); p < 0.001)) and coronary heart disease (50.6% vs. 38.0%; p < 0.011). Preoperative embolization was significantly higher within INVE (35.5% vs. 16.4%; p < 0.001) with high incidence of cerebral embolization (18.6% vs. 7.6%; p = 0.001) and underwent emergency curative surgery than the IPVE group (19.6% vs. 10.6%; p < 0.001). However, patients with IPVE were significantly represented with intracardiac abscess (44.4% vs.15.7%; p < 0.001). Intraoperatively, the duration of surgery was expectedly significantly higher in the IPVE group (356 min vs. 244 min.; p = 0.001) as well as transfusion of blood (4 units (0–27) vs. 2 units (0–14); p < 0.001). Post-operatively, the incidence of bleeding was markedly higher within the IPVE group (700 mL (438; 1163) vs. 500 mL (250; 1075); p = 0.005). IPVE required significantly more permanent pacemakers (17.6% vs. 7.5%: p = 0.002). The 30-day mortality was higher in the IPVE group (24.6% vs. 13.2%; p < 0.003). Conclusion: Patients with INVE suffered from a higher incidence of cerebral embolization and neurological deficits than patients with IPVE. Surgical treatment in INVE is performed mostly as an emergency indication. However, patients with IPVE were represented commonly with intracardiac abscess, and had a higher indication of pacemaker implantation. The short- and long-term mortality rate among those patients was still high.

Short- and long-term effects of a neonatal exposure to benzo(a)pyrene (BaP) or 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) on behaviour of rat pups

2006 ◽  
Vol 164 ◽  
pp. S80-S81 ◽  
Author(s):  
Jérôme Boussel ◽  
Nathalie Grova ◽  
Cyril Feidt ◽  
Didier Desor ◽  
Guido Rychen ◽  
...  
Keyword(s):  
Neonatal Exposure ◽  
Long Term Effects ◽  
Rat Pups ◽  
Short And Long Term

scholarly journals Neuroprotective Effects of a Combined Therapy With Memantine, Donepezil and Vitamin D in Ovariectomized Female Mice Subjected to Dementia Model

2021 ◽  
Author(s):  
Ana Daniela Coutinho Vieira ◽  
Eduarda Behenck Medeiros ◽  
Gabriel Casagrande Zabot ◽  
Nathalia de Souza Pereira ◽  
Natália Baltazar do Nascimento ◽  
...  
Keyword(s):  
Vitamin D ◽  
Combined Therapy ◽  
Neuroprotective Effects ◽  
Female Mice ◽  
Beneficial Effects ◽  
Gfap Immunoreactivity ◽  
Short And Long Term ◽  
Triple Treatment ◽  
Inflammation Parameters

Abstract The postmenopausal period is characterized by a decrease in the hormonal supply which is associated with Alzheimer's Disease (AD). Vitamin D is neuroprotective and can be used in combination with pre-existing medications to improve its effects. The objective was to evaluate the effect of vitamin D associated with memantine and donepezil in female mice submitted to ovariectomy (OVX) for 5 months and subjected to an AD-induced dementia model. Animals were divided into 5 groups who received 17 days of treatment and were subjected to behavioral tests. The animals underwent euthanasia at 18th day. OVX groups exhibit reduced levels of E2 and triple treatment group had high levels of vitamin D. The induction of dementia with OVX induced short- and long-term spatial and habituation memories damage. Also, induced reduction of BDNF and IL-4 levels in hippocampus, and increasing levels of TNFα in hippocampus and of IL-1β in hippocampus and frontal cortex of animals, as well as a significant increase on GFAP immunoreactivity. Triple-association treatment reversed the effects of long-term spatial and habituation memories damage, as well as reversed changes in TNFα, IL-1β, IL-4 and GFAP immunoreactivity levels in hippocampus of treated animals. Therapeutic association has beneficial effects on memory and inflammation parameters in female mice subjected to OVX and the AD animal model of dementia.

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