P4-215: NEUROPROTECTIVE EFFECTS OF ASTAXANTHINE AND ACETYL-L-CARNITINE AGAINST STREPTOZOTOCIN-INDUCED NEUROTOXICITY IN AGED MICE

2006 ◽  
Vol 14 (7S_Part_29) ◽  
pp. P1523-P1523
Author(s):  
Neethu Gopal ◽  
Sridharan Manavalan ◽  
Kumar Ponnusamy
Keyword(s):  
Neuroprotective Effects ◽  
Aged Mice

scholarly journals Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice

2018 ◽  
Vol 19 (9) ◽  
pp. 2615
Author(s):  
Julia Relat ◽  
Julio Come ◽  
Belen Perez ◽  
Pelayo Camps ◽  
Diego Muñoz-Torrero ◽  
...  
Keyword(s):  
Chronic Treatment ◽  
Brain Dysfunction ◽  
Male Mice ◽  
Inhibitory Effects ◽  
Middle Aged ◽  
Neuroprotective Effects ◽  
Aged Mice ◽  
Aβ Aggregation ◽  
Inflammatory Processes ◽  
Inflammatory Proteins

Molecular factors involved in neuroprotection are key in the design of novel multitarget drugs in aging and neurodegeneration. AVCRI104P3 is a huprine derivative that exhibits potent inhibitory effects on human AChE, BuChE, and BACE-1 activities, as well as on AChE-induced and self-induced Aβ aggregation. More recently, cognitive protection and anxiolytic-like effects have also been reported in mice treated with this compound. Now, we have assessed the ability of AVCRI104P3 (0.43 mg/kg, 21 days) to modulate the levels of some proteins involved in the anti-apoptotic/apoptotic processes (pAkt1, Bcl2, pGSK3β, p25/p35), inflammation (GFAP and Iba1) and neurogenesis in C57BL/6 mice. The effects of AVCRI104P3 on AChE-R/AChE-S isoforms have been also determined. We have observed that chronic treatment of C57BL/6 male mice with AVCRI104P3 results in neuroprotective effects, increasing significantly the levels of pAkt1 and pGSK3β in the hippocampus and Bcl2 in both hippocampus and cortex, but slightly decreasing synaptophysin levels. Astrogliosis and neurogenic markers GFAP and DCX remained unchanged after AVCRI104P3 treatment, whereas microgliosis was found to be significantly decreased pointing out the involvement of this compound in inflammatory processes. These results suggest that the neuroprotective mechanisms that are behind the cognitive and anxiolytic effects of AVCRI104P3 could be partly related to the potentiation of some anti-apoptotic and anti-inflammatory proteins and support the potential of AVCRI104P3 for the treatment of brain dysfunction associated with aging and/or dementia.

Abstract WMP77: SUMO1 Plays an Important Role in Cardiac Dysfunction After Intracerebral Hemorrhage in Aged Mice

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Wei Li ◽  
Michael Chopp ◽  
Poornima Venkat ◽  
Zhili Chen ◽  
Alex Zacharek ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Cardiac Dysfunction ◽  
Calcium Binding ◽  
Contractile Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Wild Type ◽  
Neuroprotective Effects ◽  
Ventricular Ejection Fraction ◽  
Aged Mice

Background: The conjugation of the small ubiquitin-like modifier1 (SUMO1) plays an important role in numerous biological processes, including DNA repair and signal transduction. SUMO1 also reduces cardiac oxidative stress and hypertrophy as well as induces neuroprotective effects. Intracerebral hemorrhage (ICH) induces cardiac deficit in the absence of primary cardiac diseases in young adult wild type mice. In this study, we tested the hypothesis that SUMO1 plays a key role in regulating brain-heart interaction after ICH, and SUMO1 deficit leads to worse brain and heart deficit after ICH in aged mice. Methods: Aged (16-20 months) female Sumo1-deficient (SUMO1-/-) mice or wild-type (SUMO1+/+) mice were subjected to ICH by injecting collagenase IV into the basal ganglia. Cardiac function was measured by echocardiography before ICH induction and at 7 days after ICH. Modified neurological severity (mNSS) ,foot-fault and adhesive removal tests were performed at 1, 3, 6 days after ICH to investigate neurological function. Cognitive functional tests (odor and novel objective tests) were performed before sacrificing the mice at 10 days after ICH, and then histological and immunohistochemically staining were used to evaluate the mechanisms. Results: Compared to SUMO1+/+ mice, SUMO1-/- mice did not exhibit significant cardiac deficit before ICH in aged mice. Compared to SUMO1+/+ICH mice, SUMO1-/-ICH mice exhibit significantly (p<0.05) increased: 1) brain hemorrhage volume and induced worse neurological and cognitive deficits, 2) cardiac dysfunction identified by decreased cardiac contractile function measured by left ventricular ejection fraction (LVEF) and fractional shortening (FS); 3) cardiac hypertrophy and fibrosis; 4) ionized calcium binding adaptor molecule (IBA1) positive macrophages/microglia and CD45 positive leukocyte infiltration into both heart and brain tissue. Conclusions: Aged SUMO1 deficient mice subjected to ICH not only exhibit increased neurological and cognitive functional deficit, but also significantly increased cardiac dysfunction and inflammatory cell infiltration into heart. These data suggest that SUMO1 plays an important role in brain-heart interaction and SUMO1 impacts brain-cardiac dysfunction after ICH.

scholarly journals Neuroprotective Effects of Kinin B2 Receptor in Organotypic Hippocampal Cultures of Middle-Aged Mice

2019 ◽  
Vol 11 ◽  
Author(s):  
Mariana Toricelli ◽  
Sebastiana Ribeiro Evangelista ◽  
Larissa Rolim Oliveira ◽  
Tania Araujo Viel ◽  
Hudson Sousa Buck
Keyword(s):  
Middle Aged ◽  
Neuroprotective Effects ◽  
Aged Mice ◽  
Hippocampal Cultures

Abstract TMP36: Exogenous Oxytocin Confers Significant Neuroprotective Effects and Improves Recovery in Young and Aged Animals After Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Juneyoung Lee ◽  
Yan Xu ◽  
Diego Morales Scheihing ◽  
Louise McCullough ◽  
Venugopal Reddy Venna
Keyword(s):  
Neuroprotective Effect ◽  
Control Group ◽  
Male Mice ◽  
Behavioral Recovery ◽  
Neuroprotective Effects ◽  
Delayed Treatment ◽  
Aged Mice ◽  
Beneficial Effects ◽  
Human Use ◽  
To Receive

Introduction: Oxytocin (OXT) is a highly evolutionary conserved neuropeptide and an important modulator of inflammation in response to stressors such as ischemia. Recent studies have implicated OXT signaling in neuroprotection in young mice after ischemic injury, but it is not known if OXT is efficacious in aged animals. In our ongoing studies, we found that OXT levels decline after stroke and with age. Therefore, we tested if exogenous OXT administration could provide beneficial effects and improve recovery in aged animals. Methods: Aged (18-20m) C57BL/6 male mice were purchased from Jax Labs and aged in house. Stroke was induced by a right MCAO-60min. Mice were randomly assigned to receive OXT or Atosiban, an OXT antagonist (OXTA) (0.5mg/kg) or vehicle. In the first set of experiments, aged mice were pre-treated with OXT, vehicle, or OXTA for 10 days before stroke. Infarcts were quantified 7-days after stroke (n=6-9/grp). In a second set, we tested the efficacy of delayed treatment, at 3hrs after stroke, and OXT was administered intranasally or i.p.. Functional and behavioral recovery and brain infarct size was assessed 7-day post-stroke. OXT levels 24hrs after stroke in human plasma were measured. Results: OXT treatment (0.5mg/kg/i.p. QD) prior to stroke led to significant neuroprotection in aged male mice, whereas OXTA treatment significantly increased infarct (p<0.05, n=6-9/grp) compared to control group (total: 39.4±2.9% control; 20.8±3.1% OXT; 51.3±2.8% OXTA). Importantly, no differences in cerebral blood flow or temperature were seen between groups. Interestingly, the neuroprotective effect of OXT treatment was observed even when treatment was initiated 3hrs (administered either i.p. or nasally) after stroke onset. Also, we observed a significant decrease in circulating OXT levels at 24hrs in stroke patients (n=26) compared to healthy controls, highlighting the translational relevance of this pathway. Conclusions: We found that OXT treatment either before or after stroke is neuroprotective in aged mice and both i.p. and nasal OXT administration improves recovery in parallel to reductions in brain injury. Given that intranasal formulations of OXT are approved for human use, our proposed strategy of supplementing OXT is highly translatable.

scholarly journals Ruscogenin alleviates cognitive dysfunction by inhibiting the activation of isoflurane-induced NLRP3 inflammasome in aged mice

2021 ◽  
Vol 13 (3) ◽  
pp. 109-115
Author(s):  
Xiaohu Liang ◽  
Xiaoqun Luo ◽  
Danping Li ◽  
Lingqiong Kong
Keyword(s):  
Cognitive Dysfunction ◽  
Calcium Binding ◽  
Neuronal Damage ◽  
Postoperative Cognitive Dysfunction ◽  
Neuron Specific Enolase ◽  
Morris Water Maze Test ◽  
Neuroprotective Effects ◽  
Necrosis Factor Alpha ◽  
Aged Mice ◽  
Pyrin Domain

Ruscogenin exerts an anti-inflammatory effect in the pathogenesis of various human diseases, including pulmonary hypertension, acute lung injury, acute pancreatitis and cerebral ischemia. Its role in isoflurane-induced rats with postoperative cognitive dysfunction (POCD) was investigated in this study. Aged rats were exposed to isoflurane for establishing a model of POCD, and administered with ruscogenin by gavage. Cognitive dysfunction was evaluated by the Morris water maze test. Hematoxylin and Eosin (H&E) staining was designed to assess neuronal damage. Markers of brain damage and neuroinflammation were detected by enzyme-linked-immunosorbent serologic assay. Isoflurane exposure caused impaired cognitive function by increasing escape latency, decreasing the time taken for crossing target and time in target quadrant. However, administration of ruscogenin reversed these cognitive dysfunctions. Abnormal morphological phenomena on neurons and enhanced levels of serum calcium-binding protein β (S-100β) and neuron-specific enolase (NSE) were identified in mice post-isoflurane exposure. Administration of ruscogenin ameliorated the neuronal morphological damages and reduced the levels of S-100β and NSE in the hippocampi of isoflurane-induced aged mice. Ruscogenin also attenuated isoflurane-induced enhancements in the levels of Interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha in the hippocampi of mice. Isoflurane-induced enhancements in the mRNA expression levels of NLR family pyrin domain containing 3 (NLRP3), ASC, IL-1β and IL-18 proteins were also restored by administration of ruscogenin. Ruscogenin exerted neuroprotective effects against isoflurane-induced cognitive dysfunction and neuroinflammation through blocking of NLRP3 pathway.

scholarly journals Netrin-1 Ameliorates Postoperative Delirium-like Behavior in Aged Mice by Suppressing Neuroinflammation and Restoring Impaired Blood Brain Barrier Permeability

2020 ◽  
Author(s):  
Ke Li ◽  
Jiayu Wang ◽  
Lei Chen ◽  
Meimei Guo ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Blood Brain Barrier ◽  
Postoperative Delirium ◽  
Axonal Guidance ◽  
Brain Barrier ◽  
Cell Junction ◽  
Chromosomal Protein ◽  
Neuroprotective Effects ◽  
Aged Mice ◽  
Blood Brain

Abstract Background Postoperative delirium (POD) is a common and serious postoperative complication in elderly patients, of which the underlying mechanism is elusive and without effective therapy at present. In recent years, the neuroinflammatory hypothesis has been developed in the pathogenesis of POD. Netrin-1, an axonal guidance molecule, has been reported to have strong inflammatory regulatory and neuroprotective effects.Methods We applied treatment with Netrin-1(45 µg/kg) in aged mice by using the POD model with a simple laparotomy to assess systemic inflammatory, neuroinflammation by detecting interleukin-6 (IL-6), interleukin-10 (IL-10), high mobility group box chromosomal protein-1(HMGB-1) and assessing the reactive states of microglia, permeability of blood-brain barrier (BBB) by detecting cell junction proteins and leakage of dextran, and behavior of the aged mice.Results We found that a single dose of Netrin-1 prophylaxis decreased the expression of IL-6 and HMGB-1, and upregulated the expression of IL-10 in peripheral blood, hippocampus and prefrontal cortex. Nerin-1 reduced activation of microglia cells in the hippocampus and prefrontal cortex and improved the POD-like behavior. Besides, Netrin-1 also attenuated the anesthesia/surgery-induced increase in BBB permeability by up-regulating the expression of tight junction-associated proteins such as ZO-1, claudin-5, and occludin.Conclusions These findings confirm the anti-inflammatory and BBB protective effects of Netrin-1 in an inflammatory environment in vivo and provide better insights into the pathophysiology and potential treatment of POD.

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