Current neurovascular research
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High glucose driven reactive oxygen intermediates production and inflammatory damage are recognized contributors of nerve dysfunction and subsequent damage in diabetic neuropathy. Sulforaphane, a known chemotherapeutic agent holds a promise for diabetic neuropathy because of its dual antioxidant and anti-inflammatory activities. The present study investigated the effect of sulforaphane in streptozotocin (STZ) induced diabetic neuropathy in rats. ⋯ Nuclear factor-kappa B (NF-κB) inhibition seemed to be responsible for antiinflammatory activity of sulforaphane as there was reduction in NF-κB expression and IκB kinase (IKK) phosphorylation along with abrogation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6) levels. Here in this study we provide an evidence that sulforaphane is effective in reversing the various deficits in experimental diabetic neuropathy. This study supports the defensive role of Nrf2 in neurons under conditions of oxidative stress and also suggests that the NF-κB pathway is an important modulator of inflammatory damage in diabetic neuropathy.
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Chronic stress can cause emotional dysfunction, but exposure to an enriched environment (EE) can benefit emotional homeostasis. Recent studies have demonstrated that EE can ameliorate stress-induced depressive-like behaviors. Whether hypothalamic-pituitary-adrenal (HPA) axis activity and corticosteroid receptors are involved in these effects of EE is not known. ⋯ These effects were ameliorated by EE. Also we found that 21 days of restraint stress resulted in low HPA axis activity, and a reduction of MR mRNA and MR/GR ratio in the hippocampus of rats, which was restored by EE. Thus, our current results emphasizes the efficiency of EE in the amelioration of stress-induced decrease in the mRNA expression of MR and MR/GR ratio as well as behavioral depression, providing initial evidence for a possible mechanism by which an enriched environment can restore stress-induced deficits.
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An enriched environment (EE) is beneficial in modifying behaviors, particularly in tasks involving complex cognitive functions. However, the impact of EE on cognitive impairment induced by chronic cerebral hypoperfusion (CCH) has not been studied. We investigated the effects of EE on cognitive impairment caused by CCH and examined whether CCH altered the protein levels of brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate (NMDA) receptor subunit 1 (NR1) and subunit 2B (NR2B) in the hippocampus of rats and whether EE exposure attenuated the effects. ⋯ CCH resulted in decreased levels of BDNF and NR1 protein in the hippocampus, and EE exposure restored the decreased expression. Our results demonstrate for the first time that EE exposure restores cognitive impairment induced by CCH and up-regulates the decreased protein levels of BDNF and NR1. Inversely, BDNF and NR1 may contribute to the beneficial effects of EE on CCH in rats.
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Traumatic spinal cord injury (SCI) disrupts the blood-spinal cord barrier and reduces the blood supply caused by microvascular changes. Vessel regression and neovascularization have been observed in the course of secondary injury contributing to microvascular remodeling after trauma. Spatio-temporal distribution of blood vessels and modulation of gene expression of several angiogenic factors have been investigated in rats after spinal cord compression injury. ⋯ Hepatocyte growth factor (HGF) was the only angiogenic factor with a constant increased gene expression when compared with controls, starting at day 3 post-SCI. mRNA levels of transforming growth factor-beta 1 (TGF-β1) were elevated at every time point following SCI, whereas those encoding for the cysteine-rich protein CCN1/CYR61 were upregulated after 2 h, 6 h, and 1 week only. Our data provide an overview of the temporal modulated expression of the major angiogenic factors, hampering revascularization in the lesion during the phase of secondary injury. These findings should be considered in order to improve therapeutic interventions.
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One of the therapeutics for acute cerebral ischemia is tissue plasminogen activator (t-PA). Using t-PA after 3 hour time window increases the chances of hemorrhage, involving multiple mechanisms. In order to show possible mechanisms of t-PA toxicity and the effect of the free radical scavenger edaravone, we administered vehicle, plasmin, and t-PA into intact rat cortex, and edaravone intravenously. ⋯ Such damage to tight junctions was recovered in t-PA plus edaravone group with similar recovery in Sodium-Fluorescein permeability assay. Administration of t-PA caused oxidative stress damage to lipids, proteins and DNA, and led to disruption of outer parts of neurovascular unit, greater than the effect in plasmin administration. Additive edaravone ameliorated such an oxidative damage by t-PA with protecting outer layers of blood-brain barrier (in vivo) and tight junctions (in vitro).