Experimental biology and medicine
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Exp. Biol. Med. (Maywood) · Mar 2009
Environmental enrichment induces synaptic structural modification after transient focal cerebral ischemia in rats.
Environmental enrichment (EE), where animals are exposed to a complex novel environment, has been shown to induce synaptic plasticity in both intact and injured animals. The purpose of this study was to investigate the effects of EE on spatial memory and structural modifications of synaptic junctions in rats following transient focal cerebral ischemia. Adult male Sprague-Dawley rats underwent right middle cerebral artery occlusion (MCAO) for 40 min and reperfusion. ⋯ The results showed that the content of NMDAR1 was not altered in MCAO rats of EE; however, the phosphorylated NMDAR1 increased significantly when compared with the standard environment housing MCAO rats. In addition, EE inhibited the impaired expression of PSD-95 induced by MCAO in parietal cortex and hippocampus. These data suggest that improved spatial memory of cerebral ischemic rats by EE is associated with structural modifications of synaptic junctions in several brain regions.
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Exp. Biol. Med. (Maywood) · Feb 2009
Genetic ablation of Nrf2 enhances susceptibility to acute lung injury after traumatic brain injury in mice.
Previous studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. The present study investigated the role of Nrf2 in the regulation of traumatic brain injury (TBI)-induced acute lung injury (ALI). Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. ⋯ Mice lacking Nrf2 were found to be more susceptible to TBI-induced ALI, as characterized by the higher increase in PCP, wet/dry weight ratio and alveolar cells apoptosis after TBI. This exacerbation of lung injury in Nrf2-deficient mice was associated with increased pulmonary mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6); and with decreased pulmonary mRNA expression and enzymatic activities of antioxidant and detoxifying enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha1 (GST-alpha1)--as compared with their wild-type Nrf2 (+/+) counterparts after TBI. The results of the present study suggest that Nrf2 reduces TBI-induced acute lung injury, possibly by decreasing pulmonary inflammation and inducing antioxidant and detoxifying enzymes.
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Exp. Biol. Med. (Maywood) · Feb 2009
Role of protease-activated receptor-1 in endothelial nitric oxide synthase-Thr495 phosphorylation.
Protease activated receptors (PARs) are G protein-coupled receptors that are known to regulate endothelial nitric oxide synthase (eNOS) activity in part by phosphorylating the enzyme at various sites. Ser1177 is a positive regulatory site, which leads to the enhanced production of nitric oxide (NO), a vasodilator of arteries. Thr495 is a negative regulatory site, which inhibits NO production. ⋯ Blockade of the Rho/ROCK pathway also caused an increase in nitrite production. This suggests that PAR-1 regulates eNOS activity via phosphorylation of eNOS-Thr495, which is dependent upon activation of the Rho/ROCK pathway. These findings will be beneficial in further understanding the signaling pathways that regulate eNOS-induced NO production, which plays an important role in endothelial dysfunction associated with cardiovascular disease.
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Exp. Biol. Med. (Maywood) · Sep 2008
High plasma levels of MCP-1 and eotaxin provide evidence for an immunological basis of fibromyalgia.
Fibromyalgia (FMS), a predominantly female (85%) syndrome, affects an estimated 2% of the US population with skeletal muscle ache, fatigue, headache, and sleep disorder. The pathogenesis of FMS is unknown and there is no laboratory test for diagnosis. In this study, plasma levels of 25 cytokines and chemokines in 92 female patients with FMS and 69 family members were measured compared to 77 controls. ⋯ Furthermore, myoblasts can secrete MCP-1, eotaxin, and IP-10, while treatment with MCP-1 caused secretion of IL-1beta, eotaxin and IP-10. FMS is associated with inflammatory chemokines, that MCP-1 and eotaxin may contribute to the symptoms of FMS, and that similar cytokine profiles found in family members support the idea that FMS has a genetic component. Furthermore, the chemokine profile associated with FMS has direct effects on the migration of eosinophils and monocytes in the presence of mast cells, and skeletal muscle itself may secrete.
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Exp. Biol. Med. (Maywood) · Aug 2008
ReviewCurrent management of the cognitive dysfunction in Parkinson's disease: how far have we come?
Parkinson's disease (PD) clinical features comprise both motor and nonmotor manifestations. Among the nonmotor complications, dementia is the most important. Approximately 40% of PD patients are affected by cognitive impairment. ⋯ Preliminary studies with vehicles that may target PDpFCD include piribedil, tolcapone, amantadine, and farampator. Additional agents (citicoline and neuroimmuniphilines, among others) will be outlined. A brief overview on neuroprotection and promising new biological advances in PD (deep brain stimulation, stem cells, gene therapy) also will be summarized.