Journal of neurochemistry
-
Journal of neurochemistry · Nov 2014
Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture.
Bone fracture at the acute stage of stroke exacerbates stroke injury by increasing neuroinflammation. We hypothesize that activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) attenuates neuroinflammation and oxidative stress, and reduces brain injury in mice with bone fracture and stroke. Permanent middle cerebral artery occlusion (pMCAO) was performed in C57BL/6J mice followed by tibia fracture 1 day later. ⋯ Our data indicate that α-7 nAchR agonist treatment reduces neuroinflammation and oxidative stress, which are associated with reduced brain injury in mice with ischemic stroke plus tibia fracture. Bone fracture at the acute stage of stroke exacerbates neuroinflammation, oxidative stress, and brain injury, and our study has shown that the α-7 nAchR agonist, PHA (PHA 568487), attenuates neuroinflammation, oxidative stress, and brain injury in mice with stroke and bone fracture. Hence, PHA could provide an opportunity to develop a new strategy to reduce brain injury in patients suffering from stroke and bone fracture.
-
Journal of neurochemistry · Nov 2014
Reactive oxygen species and lipid peroxidation inhibitors reduce mechanical sensitivity in a chronic neuropathic pain model of spinal cord injury in rats.
Chronic neuropathic pain is a common consequence of spinal cord injury (SCI), develops over time and negatively impacts quality of life, often leading to substance abuse and suicide. Recent evidence has demonstrated that reactive oxygen species (ROS) play a role in contributing to neuropathic pain in SCI animal models. This investigation examines four compounds that reduce ROS and the downstream lipid peroxidation products, apocynin, 4-oxo-tempo, U-83836E, and tirilazad, and tests if these compounds can reduce nocioceptive behaviors in chronic SCI animals. ⋯ Injury or trauma to nervous tissue leads to increased concentrations of ROS in the surviving tissue. Further damage from ROS molecules to dorsal lamina neurons leads to membrane excitability, the physiological correlate of chronic pain. Chronic pain is difficult to treat with current analgesics and this research will provide a novel therapy for this disease.
-
Journal of neurochemistry · Nov 2014
Nerve growth factor inhibits osmotic swelling of rat retinal glial (Müller) and bipolar cells by inducing glial cytokine release.
Osmotic swelling of neurons and glial cells contributes to the development of retinal edema and neurodegeneration. We show that nerve growth factor (NGF) inhibits the swelling of glial (Müller) and bipolar cells in rat retinal slices induced by barium-containing hypoosmotic solution. NGF also reduced Müller and bipolar cell swelling in the post-ischemic retina. ⋯ Cytotoxic cell swelling contributes to retinal neurodegeneration. Nerve growth factor (NGF) inhibits the osmotic swelling of glial cells by acting at TrkA, release of bFGF, and opening of K(+) and Cl(-) channels. The NGF-induced glial release of cytokines like bFGF inhibits the osmotic swelling of bipolar cells, suggesting that the neuroprotective effect of NGF is in part mediated by prevention of cytotoxic cell swelling.
-
Journal of neurochemistry · Nov 2014
Striatal serotonin 2C receptors decrease nigrostriatal dopamine release by increasing GABA-A receptor tone in the substantia nigra.
Drugs acting at the serotonin-2C (5-HT2C) receptor subtype have shown promise as therapeutics in multiple syndromes including obesity, depression, and Parkinson's disease. While it is established that 5-HT2C receptor stimulation inhibits DA release, the neural circuits and the localization of the relevant 5-HT2C receptors remain unknown. This study used dual-probe in vivo microdialysis to investigate the relative contributions of 5-HT2C receptors localized in the rat substantia nigra (SN) and caudate-putamen (CP) in the control of nigrostriatal DA release. ⋯ Using in vivo microdialysis, we demonstrated that blockade of serotonin (5-HT) 2C receptors in the CP increased nigrostriatal DA release. Infusions of a GABA-A agonist into the substantia nigra pars reticulata (SNpr) blocked this increase. This work indicates that striatal serotonin 2C receptors regulate GABAergic tone in the SNpr, which in turn regulates nigrostriatal DA release.