Browsing by Subject "Neuroprotection"

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  • Alshami, Abbas; Einav, Sharon; Skrifvars, Markus B.; Varon, Joseph (2020)
    Objective: Inhalation of noble and other gases after cardiac arrest (CA) might improve neurological and cardiac outcomes. This article discusses up-to-date information on this novel therapeutic intervention. Data sources: CENTRAL, MEDLINE, online published abstracts from conference proceedings, clinical trial registry, and reference lists of relevant papers were systematically searched from January 1960 till March 2019. Study selection: Preclinical and clinical studies, irrespective of their types or described outcomes, were included. Data extraction: Abstract screening, study selection, and data extraction were performed by two independent authors. Due to the paucity of human trials, risk of bias assessment was not performed DATA SYNTHESIS: After screening 281 interventional studies, we included an overall of 27. Only, xenon, helium, hydrogen, and nitric oxide have been or are being studied on humans. Xenon, nitric oxide, and hydrogen show both neuroprotective and cardiotonic features, while argon and hydrogen sulfide seem neuroprotective, but not cardiotonic. Most gases have elicited neurohistological protection in preclinical studies; however, only hydrogen and hydrogen sulfide appeared to preserve CA1 sector of hippocampus, the most vulnerable area in the brain for hypoxia. Conclusion: Inhalation of certain gases after CPR appears promising in mitigating neurological and cardiac damage and may become the next successful neuroprotective and cardiotonic interventions. (C) 2020 Elsevier Inc. All rights reserved.
  • Martiskainen, Henna; Paldanius, Kaisa M A; Natunen, Teemu; Takalo, Mari; Marttinen, Mikael; Leskelä, Stina; Huber, Nadine; Mäkinen, Petra; Bertling, Enni; Dhungana, Hiramani; Huuskonen, Mikko; Honkakoski, Paavo; Hotulainen, Pirta; Rilla, Kirsi; Koistinaho, Jari; Soininen, Hilkka; Malm, Tarja; Haapasalo, Annakaisa; Hiltunen, Mikko (BioMed Central, 2017)
    Abstract Background DHCR24, involved in the de novo synthesis of cholesterol and protection of neuronal cells against different stress conditions, has been shown to be selectively downregulated in neurons of the affected brain areas in Alzheimer’s disease. Methods Here, we investigated whether the overexpression of DHCR24 protects neurons against inflammation-induced neuronal death using co-cultures of mouse embryonic primary cortical neurons and BV2 microglial cells upon acute neuroinflammation. Moreover, the effects of DHCR24 overexpression on dendritic spine density and morphology in cultured mature mouse hippocampal neurons and on the outcome measures of ischemia-induced brain damage in vivo in mice were assessed. Results Overexpression of DHCR24 reduced the loss of neurons under inflammation elicited by LPS and IFN-γ treatment in co-cultures of mouse neurons and BV2 microglial cells but did not affect the production of neuroinflammatory mediators, total cellular cholesterol levels, or the activity of proteins linked with neuroprotective signaling. Conversely, the levels of post-synaptic cell adhesion protein neuroligin-1 were significantly increased upon the overexpression of DHCR24 in basal growth conditions. Augmentation of DHCR24 also increased the total number of dendritic spines and the proportion of mushroom spines in mature mouse hippocampal neurons. In vivo, overexpression of DHCR24 in striatum reduced the lesion size measured by MRI in a mouse model of transient focal ischemia. Conclusions These results suggest that the augmentation of DHCR24 levels provides neuroprotection in acute stress conditions, which lead to neuronal loss in vitro and in vivo.
  • Sarajärvi, T.; Jäntti, M.; Paldanius, K. M. A.; Natunen, T.; Wu, J. C.; Mäkinen, P.; Tarvainen, I.; Tuominen, R. K.; Talman, V.; Hiltunen, M. (2018)
    Abnormal protein kinase C (PKC) function contributes to many pathophysiological processes relevant for Alzheimer's disease (AD), such as amyloid precursor protein (APP) processing. Phorbol esters and other PKC activators have been demonstrated to enhance the secretion of soluble APP alpha (sAPP alpha), reduce the levels of beta-amyloid (A beta), induce synaptogenesis, and promote neuroprotection. We have previously described isophthalate derivatives as a structurally simple family of PKC activators. Here, we characterised the effects of isophthalate derivatives HMI-1a3 and HMI-1b11 on neuronal viability, neuroinflammatory response, processing of APP and dendritic spine density and morphology in in vitro. HMI-1a3 increased the viability of embryonic primary cortical neurons and decreased the production of the pro-inflammatory mediator TNF alpha, but not that of nitric oxide, in mouse neuron-BV2 microglia co-cultures upon LPS- and IFN-gamma-induced neuroinflammation. Furthermore, both HMI-1a3 and HMI-1b11 increased the levels of sAPPa relative to total sAPP and the ratio of A beta 42/A beta 40 in human SH-Sv5v neuroblastoma cells. Finally, bryostatin-1, but not HMI-1a3, increased the number of mushroom spines in proportion to total spine density in mature mouse hippocampal neuron cultures. These results suggest that the PKC activator HMI-1a3 exerts neuroprotective functions in the in vitro models relevant for AD by reducing the production of TNF alpha and increasing the secretion of neuroprotective sAPPa.