Neuroprotection by 4R-cembranoid against Gulf War Illness-related Chemicals is mediated by ERK, PI3K, and CaMKII pathways.

Gulf War Illness (GWI) has been consistently linked to exposure to pyridostigmine (PB), N,N-Diethyl-meta-toluamide (DEET), permethrin (PER), and traces of sarin. In this study, diisopropylfluorophosphate (DFP, sarin surrogate) and the GWI-related chemicals were found to reduce the number of functionally active neurons in rat hippocampal slices. These findings confirm a link between GWI neurotoxicants and N-Methyl-D-Aspartate (NMDA)-mediated excitotoxicity, which was successfully reversed by Edelfosine (a phospholipase Cβ (PLCβ3) inhibitor) and Flupirtine (a Kv7 channel agonist).

Determining the safety of the tobacco cembranoid (1S,2E,4R,6R,7E,11E)-Cembratriene-4,6-diol (4R): A translational study in nonhuman primates.

The tobacco cembranoid known as (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (4R) has been shown to offer neuroprotection against conditions such as brain ischemia, systemic inflammation, Parkinson's disease, and organophosphate toxicity in rodents. Previous safety studies conducted on male and female Sprague Dawley rats revealed no significant side effects following a single injection of 4R at varying concentrations (6, 24, or 98 mg/kg of body weight). This study aimed to assess the potential of 4R for clinical trials in neurotherapy in male nonhuman primates.

4R-cembranoid confers neuroprotection against LPS-induced hippocampal inflammation in mice.

Background: Chronic brain inflammation has been implicated in the pathogenesis of various neurodegenerative diseases and disorders. For example, overexpression of pro-inflammatory cytokines has been associated with impairments in hippocampal-dependent memory. Lipopolysaccharide (LPS) injection is a widely used model to explore the pathobiology of inflammation.

Neuroprotective activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in rodent models of brain ischemia.

(1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is a precursor to key flavor ingredients in leaves of Nicotiana species. The present study shows 4R decreased brain damage in rodent ischemic stroke models. The 4R-pretreated mice had lower infarct volumes (26.

Protective activity of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol analogues against diisopropylfluorophosphate neurotoxicity: preliminary structure-activity relationship and pharmacophore modeling.

Diisopropylfluorophosphate (DFP) is an organophosphorous insecticide used as a surrogate for the more toxic chemical warfare nerve agent sarin. DFP produces neurotoxicity in vivo and irreversibly decreases the area of population spikes recorded from the CA1 region of acute hippocampal slices. (1S,2E,4R,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) is a neuroprotective natural cembranoid that reverses DFP-induced damage both in vivo and in the hippocampal slice.

Acute neuronal injury and blood genomic profiles in a nonhuman primate model for ischemic stroke.

The goal of this study was to characterize acute neuronal injury in a novel nonhuman primate (NHP) ischemic stroke model by using multiple outcome measures. Silk sutures were inserted into the M1 segment of the middle cerebral artery of rhesus macaques to achieve permanent occlusion of the vessel. The sutures were introduced via the femoral artery by using endovascular microcatheterization techniques.

Kinin-B2 receptor mediated neuroprotection after NMDA excitotoxicity is reversed in the presence of kinin-B1 receptor agonists.

Background: Kinins, with bradykinin and des-Arg(9)-bradykinin being the most important ones, are pro-inflammatory peptides released after tissue injury including stroke. Although the actions of bradykinin are in general well characterized; it remains controversial whether the effects of bradykinin are beneficial or not. Kinin-B2 receptor activation participates in various physiological processes including hypotension, neurotransmission and neuronal differentiation.

Genetic program of neuronal differentiation and growth induced by specific activation of NMDA receptors.

Glutamate and its receptors are expressed very early during development and may play important roles in neurogenesis, synapse formation and brain wiring. The levels of glutamate and activity of its receptors can be influenced by exogenous factors, leading to neurodevelopmental disorders. To investigate the role of NMDA receptors on gene regulation in a neuronal model, we used primary neuronal cultures developed from embryonic rat cerebri in serum-free medium.

Gene expression is differentially regulated by neurotransmitters in embryonic neuronal cortical culture.

Neurotransmitters and their receptors have been involved in both proper brain development and neurodevelopmental disorders. The role that nicotinic receptors play in immature cortical neurons was initially investigated by gene profiling using Affymetrix DNA arrays. Both short (15 min) and prolonged (18 h) treatments with nicotine did not induce modification in gene expression, whereas a significant down-regulation of c-fos protein levels was observed after 18 h treatment.