Drop in relapse rate of MS by combination therapy of three different                 phosphodiesterase inhibitors

Suzumura, Akio; Nakamuro, T; Tamaru, Tsukasa; Takayanagi, Tetsuya

doi:10.1177/135245850000600111

Cited by 20 publications

(10 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treatment of MS patients with duloxetine, a SNRI (Solaro et al 2013), reduced depression and fatigure; however, neurological symptoms were not evaluated. It has also been reported that treatment with phosphodiesterase inhibitors, which prevent breakdown of cAMP, provides benefit (Suzumura et al 2000), although it is likely that cAMP levels are due not only to NA activation of bARs but to other activators of adenylate cyclase activity. A possible explanation to account for benefit in MS but not AD is that most of the above treatments will increase peripheral as well as central NA levels, and that there is a significant involvement of peripheral immune responses in MS that can be restricted by NA.…”

Section: Vindeburnolmentioning

confidence: 99%

Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system

Feinstein

Kalinin

Braun

2016

Journal of Neurochemistry

138

128

View full text Add to dashboard Cite

Aside from its roles in as a classical neurotransmitter involved in regulation of behavior, noradrenaline (NA) has other functions in the CNS. This includes restricting the development of neuroinflammatory activation, providing neurotrophic support to neurons, and providing neuroprotection against oxidative stress. In recent years, it has become evident that disruption of physiological NA levels or signaling is a contributing factor to a variety of neurological diseases and conditions including Alzheimer's disease (AD) and Multiple Sclerosis. The basis for dysregulation in these diseases is, in many cases, due to damage occurring to noradrenergic neurons present in the locus coeruleus (LC), the major source of NA in the CNS. LC damage is present in AD, multiple sclerosis, and a large number of other diseases and conditions. Studies using animal models have shown that experimentally induced lesion of LC neurons exacerbates neuropathology while treatments to compensate for NA depletion, or to reduce LC neuronal damage, provide benefit. In this review, we will summarize the anti-inflammatory and neuroprotective actions of NA, summarize examples of how LC damage worsens disease, and discuss several approaches taken to treat or prevent reductions in NA levels and LC neuronal damage. Further understanding of these events will be of value for the development of treatments for AD, multiple sclerosis, and other diseases and conditions having a neuroinflammatory component.

show abstract

Section: Vindeburnolmentioning

confidence: 99%

Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system

Feinstein

Kalinin

Braun

2016

Journal of Neurochemistry

138

128

View full text Add to dashboard Cite

show abstract

“…The pro-inflammatory cytokines TNF-α and IL-1β, in conjunction with ROS, such as the superoxide anion radical, are important peripheral and spinal hyperalgesic mediators and therefore represent relevant targets for analgesic drug development [ 13 , 14 ]. An analgesic role for vinpocetine is supported by its clinical utility in a wide range of neuroinflammatory human diseases, including multiple sclerosis [ 15 ], intracranial birth trauma-induced seizures [ 16 ], and chronic brain ischemia [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Vinpocetine Reduces Carrageenan-Induced Inflammatory Hyperalgesia in Mice by Inhibiting Oxidative Stress, Cytokine Production and NF-κB Activation in the Paw and Spinal Cord

et al. 2015

View full text Add to dashboard Cite

Vinpocetine is a safe nootropic agent used for neurological and cerebrovascular diseases. The anti-inflammatory activity of vinpocetine has been shown in cell based assays and animal models, leading to suggestions as to its utility in analgesia. However, the mechanisms regarding its efficacy in inflammatory pain treatment are still not completely understood. Herein, the analgesic effect of vinpocetine and its anti-inflammatory and antioxidant mechanisms were addressed in murine inflammatory pain models. Firstly, we investigated the protective effects of vinpocetine in overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone (PBQ) and formalin. The intraplantar injection of carrageenan was then used to induce inflammatory hyperalgesia. Mechanical and thermal hyperalgesia were evaluated using the electronic von Frey and the hot plate tests, respectively, with neutrophil recruitment to the paw assessed by a myeloperoxidase activity assay. A number of factors were assessed, both peripherally and in the spinal cord, including: antioxidant capacity, reduced glutathione (GSH) levels, superoxide anion, tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels, as well as nuclear factor kappa B (NF-κB) activation. Vinpocetine inhibited the overt pain-like behavior induced by acetic acid, PBQ and formalin (at both phases), as well as the carrageenan-induced mechanical and thermal hyperalgesia and associated neutrophil recruitment. Both peripherally and in the spinal cord, vinpocetine also inhibited: antioxidant capacity and GSH depletion; increased superoxide anion; IL-1β and TNF-α levels; and NF-κB activation. As such, vinpocetine significantly reduces inflammatory pain by targeting oxidative stress, cytokine production and NF-κB activation at both peripheral and spinal cord levels.

show abstract

“…Clinically it has shown efficacy in degenerative vascular dementia (18) and as a potential adjuvant treatment to Alzheimer's disease (19,20), schizophrenia (21) and multiple sclerosis (22). PPF probably depresses activation of microglial cells and astrocytes, which is associated with neuronal damage during inflammation and hypoxia and consequently decreases glial production and release of damaging proinflammatory factors (16).…”

mentioning

confidence: 99%

Propentofylline reverses delayed remyelination in streptozotocin-induced diabetic rats

Bondan

Martins

Bernardi

2015

Arch. Endocrinol. Metab.

View full text Add to dashboard Cite

Objective: The diabetic state induced by streptozotocin injection is known to impair oligodendroglial remyelination in the rat brainstem following intracisternal injection with the gliotoxic agent ethidium bromide (EB). In such experimental model, propentofylline (PPF) recently showed to improve myelin repair, probably due to its neuroprotective, antiinflammatory and antioxidant effects. The aim of this study was to evaluate the effect of PPF administration in diabetic rats submitted to the EB-demyelinating model. Materials and methods: Adult male rats, diabetic or not, received a single injection of 10 microlitres of 0.1% EB solution into the cisterna pontis. For induction of diabetes mellitus the streptozotocin-diabetogenic model was used (50 mg/kg, intraperitoneal route -IP). Some diabetic rats were treated with PPF (12.5 mg/kg/day, IP route) during the experimental period. The animals were anesthetized and perfused from 7 to 31 days after EB injection and brainstem sections were collected for analysis of the lesions by light and transmission electron microscopy. Results: Diabetic rats injected with EB showed larger amounts of myelin-derived membranes in the central areas of the lesions and considerable delay in the remyelinating process played by surviving oligodendrocytes and invading Schwann cells after the 15 th day. On the other hand, diabetic rats that received PPF presented lesions similar to those of non-diabetic animals, with rapid remyelination at the edges of the lesion site and fast clearance of myelin debris from the central area. Conclusion: The administration of PPF apparently reversed the impairment in remyelination induced by the diabetic state. Arch Endocrinol Metab. 2015;59(1):47-53

show abstract

Drop in relapse rate of MS by combination therapy of three different phosphodiesterase inhibitors

Cited by 20 publications

References 9 publications

Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system

Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system

Vinpocetine Reduces Carrageenan-Induced Inflammatory Hyperalgesia in Mice by Inhibiting Oxidative Stress, Cytokine Production and NF-κB Activation in the Paw and Spinal Cord

Propentofylline reverses delayed remyelination in streptozotocin-induced diabetic rats

Contact Info

Product

Resources

About