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Joyce A Deleo - One of the best experts on this subject based on the ideXlab platform.
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Propentofylline a cns glial modulator does not decrease pain in post herpetic neuralgia patients in vitro evidence for differential responses in human and rodent microglia and macrophages
Experimental Neurology, 2012Co-Authors: Russell P Landry, Valerie L Jacobs, Edgar Alfonso Romerosandoval, Joyce A DeleoAbstract:Abstract There is a growing body of preclinical evidence for the potential involvement of glial cells in neuropathic pain conditions. Several glial-targeted agents are in development for the treatment of pain conditions. Here we report the failure of a glial modulating agent, Propentofylline, to decrease pain reported in association with post-herpetic neuralgia. We offer new evidence to help explain why Propentofylline failed in patients by describing in vitro functional differences between rodent and human microglia and macrophages. We directly compared the proinflammatory response induced by lipopolysaccharide (LPS) with or without Propentofylline using rat postnatal microglia, rat peritoneal macrophages, human fetal microglia, human peripheral macrophages and human immortalized THP-1 cells. We measured tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and nitrite release (as an indicator of nitric oxide (NO)) as downstream indicators. We found that LPS treatment did not induce nitrite in human microglia, macrophages or THP-1 cells; however LPS treatment did induce nitrite release in rat microglia and macrophages. Following LPS exposure, Propentofylline blocked TNF-α release in rodent microglia with all the doses tested (1–100 μM), and dose-dependently decreased TNF-α release in rodent macrophages. Propentofylline partially decreased TNF-α (35%) at 100 μM in human microglia, macrophages and THP-1 macrophages. Propentofylline blocked nitrite release from LPS stimulated rat microglia and inhibited nitrite in LPS-stimulated rat macrophages. IL-1β was decreased in LPS-stimulated human microglia following Propentofylline at 100 μM. Overall, human microglia were less responsive to LPS stimulation and Propentofylline treatment than the other cell types. Our data demonstrate significant functional differences between cell types and species following Propentofylline treatment and LPS stimulation. These results may help explain the differential behavioral effects of Propentofylline observed between rodent models of pain and the human clinical trial.
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Propentofylline induced astrocyte modulation leads to alterations in glial glutamate promoter activation following spinal nerve transection
Neuroscience, 2008Co-Authors: Vivianne L Tawfik, Joyce A Deleo, Melissa R Regan, Christine Haenggeli, Michael L Lacroixfralish, Nancy Nutilemcmenemy, Natalie Perez, Jeffrey D RothsteinAbstract:Abstract We have previously shown that the atypical methylxanthine, Propentofylline, reduces mechanical allodynia after peripheral nerve transection in a rodent model of neuropathy. In the present study, we sought to determine whether Propentofylline-induced glial modulation alters spinal glutamate transporters, glutamate transporter-1 (GLT-1) and glutamate-aspartate transporter (GLAST) in vivo , which may contribute to reduced behavioral hypersensitivity after nerve injury. In order to specifically examine the expression of the spinal glutamate transporters, a novel line of double transgenic GLT-1-enhanced green fluorescent protein (eGFP)/GLAST-Discosoma Red (DsRed) promoter mice was used. Adult mice received Propentofylline (10 mg/kg) or saline via i.p. injection starting 1 h prior to L5-spinal nerve transection and then daily for 12 days. Mice receiving saline exhibited punctate expression of both eGFP (GLT-1 promoter activation) and DsRed (GLAST promoter activation) in the dorsal horn of the spinal cord, which was decreased ipsilateral to nerve injury on day 12. Propentofylline administration reinstated promoter activation on the injured side as evidenced by an equal number of eGFP (GLT-1) and DsRed (GLAST) puncta in both dorsal horns. As demonstrated in previous studies, Propentofylline induced a concomitant reversal of L5 spinal nerve transection-induced expression of glial fibrillary acidic protein (GFAP). The ability of Propentofylline to alter glial glutamate transporters highlights the importance of controlling aberrant glial activation in neuropathic pain and suggests one possible mechanism for the anti-allodynic action of this drug.
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reprint of efficacy of Propentofylline a glial modulating agent on existing mechanical allodynia following peripheral nerve injury brain behav immun 21 2007 238 246
Brain Behavior and Immunity, 2007Co-Authors: Vivianne L Tawfik, Joyce A Deleo, Michael L Lacroixfralish, Nancy NutilemcmenemyAbstract:Abstract Increasing evidence points to a role for spinal neuroimmune dysregulation (glial cell activation and cytokine expression) in the pathogenesis of chronic pain. Suppression of astrocytic and microglial activation with the methylxanthine derivative, Propentofylline, pre-emptively attenuates the development of nerve injury-induced allodynia. Currently, we investigated the ability of systemic Propentofylline to reverse existing, long-term allodynia after nerve injury—a clinically relevant paradigm. Rats received L5 spinal nerve transection or sham surgery and the development of mechanical allodynia was assessed daily for 2 weeks, at which time injured rats exhibited robust responses to non-noxious von Frey filaments. On days 14–27, rats received either saline or 101 mg/kg Propentofylline by intraperitoneal (i.p.) injection. On day 28 or 42 (after a 14-day drug washout period), lumbar spinal cord sections were processed for assessment of astrocytic glial fibrillary acidic protein (GFAP) and microglial OX-42 (antibody against CR3/CD11b). Propentofylline treatment to nerve injured rats resulted in significant reversal of allodynia that lasted throughout the 14-day washout period. Spinal microglial activation was observed at days 28 and 42 post-injury at the protein level, in the absence of mRNA level changes. Less robust increases in GFAP immunoreactivity were observed at days 28 and 42 post-transection. Interestingly, Propentofylline treatment suppressed microglial activation at both time points in this paradigm. Taken together, our results highlight the clinical potential of the glial modulating agent, Propentofylline, for the treatment of neuropathic pain as well as a role for microglia in the long-term maintenance of allodynia.
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efficacy of Propentofylline a glial modulating agent on existing mechanical allodynia following peripheral nerve injury
Brain Behavior and Immunity, 2007Co-Authors: Vivianne L Tawfik, Joyce A Deleo, Michael L Lacroixfralish, Nancy NutilemcmenemyAbstract:Abstract Increasing evidence points to a role for spinal neuroimmune dysregulation (glial cell activation and cytokine expression) in the pathogenesis of chronic pain. Suppression of astrocytic and microglial activation with the methylxanthine derivative, Propentofylline, pre-emptively attenuates the development of nerve injury-induced allodynia. Currently, we investigated the ability of systemic Propentofylline to reverse existing, long-term allodynia after nerve injury—a clinically relevant paradigm. Rats received L5 spinal nerve transection or sham surgery and the development of mechanical allodynia was assessed daily for 2 weeks, at which time injured rats exhibited robust responses to non-noxious von Frey filaments. On days 14–27, rats received either saline or 101 mg/kg Propentofylline by intraperitoneal (i.p.) injection. On day 28 or 42 (after a 14-day drug washout period), lumbar spinal cord sections were processed for assessment of astrocytic glial fibrillary acidic protein (GFAP) and microglial OX-42 (antibody against CR3/CD11b). Propentofylline treatment to nerve injured rats resulted in significant reversal of allodynia that lasted throughout the 14-day washout period. Spinal microglial activation was observed at days 28 and 42 post-injury at the protein level, in the absence of mRNA level changes. Less robust increases in GFAP immunoreactivity were observed at days 28 and 42 post-transection. Interestingly, Propentofylline treatment suppressed microglial activation at both time points in this paradigm. Taken together, our results highlight the clinical potential of the glial modulating agent, Propentofylline, for the treatment of neuropathic pain as well as a role for microglia in the long-term maintenance of allodynia.
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Propentofylline attenuates vincristine induced peripheral neuropathy in the rat
Neuroscience Letters, 2006Co-Authors: Sarah M Sweitzer, Joyce A Deleo, Janice L PahlAbstract:Abstract The development of painful peripheral neuropathy is a dose-limiting side effect of numerous cancer chemotherapeutic agents. The present study utilized a rodent model of vincristine-induced neuropathy to determine whether a glial modulating agent, Propentofylline, could attenuate vincristine-induced mechanical allodynia. Intravenous vincristine administered on days 1 through 5 and days 8 through 11 produced mechanical allodynia using 2 and 12 g von Frey filaments. Lumbar spinal cord from animals on day 15 expressed mild bilateral microglial and astrocytic activation as compared to saline-treated animals. Daily intraperitoneal Propentofylline at 10 mg/kg attenuated mechanical allodynia induced by vincristine administration. In addition, Propentofylline was found to decrease spinal microglial and astrocytic activation on day 15. These data suggest that central glial cells may play an important role in the development of painful neuropathy following vincristine administration.
Vasudeva Raghavendra - One of the best experts on this subject based on the ideXlab platform.
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attenuation of morphine tolerance withdrawal induced hyperalgesia and associated spinal inflammatory immune responses by Propentofylline in rats
Neuropsychopharmacology, 2004Co-Authors: Vasudeva Raghavendra, Flobert Y Tanga, Joyce A DeleoAbstract:Attenuation of Morphine Tolerance, Withdrawal-Induced Hyperalgesia, and Associated Spinal Inflammatory Immune Responses by Propentofylline in Rats
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Attenuation of Morphine Tolerance, Withdrawal-Induced Hyperalgesia, and Associated Spinal Inflammatory Immune Responses by Propentofylline in Rats
Neuropsychopharmacology, 2004Co-Authors: Vasudeva Raghavendra, Flobert Y Tanga, Joyce A DeleoAbstract:The activation of glial cells and enhanced proinflammatory cytokine expression at the spinal cord has been implicated in the development of morphine tolerance, and morphine withdrawal-induced hyperalgesia. The present study investigated the effect of Propentofylline, a glial modulator, on the expression of analgesic tolerance and withdrawal-induced hyperalgesia in chronic morphine-treated rats. Chronic morphine administration through repeated subcutaneous injection induced glial activation and enhanced proinflammatory cytokine levels at the lumbar spinal cord. Moreover, glial activation and enhanced proinflammatory cytokine levels exhibited a temporal correlation with the expression of morphine tolerance and hyperalgesia. Consistently, Propentofylline attenuated the development of hyperalgesia and the expression of spinal analgesic tolerance to morphine. The administration of Propentofylline during the induction of morphine tolerance also attenuated glial activation and proinflammatory cytokines at the L5 lumbar spinal cord. These results further support the hypothesis that spinal glia and proinflammatory cytokines contribute to the mechanisms of morphine tolerance and associated abnormal pain sensitivity.
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anti hyperalgesic and morphine sparing actions of Propentofylline following peripheral nerve injury in rats mechanistic implications of spinal glia and proinflammatory cytokines
Pain, 2003Co-Authors: Vasudeva Raghavendra, Flobert Y Tanga, Maria D Rutkowski, Joyce A DeleoAbstract:Abstract Injury to peripheral nerves often produces non-physiological, long-lasting spontaneous pain, hyperalgesia and allodynia that are refractory to standard treatment and often insensitive to opioids, such as morphine. Recent studies demonstrate spinal glial activation and increased proinflammatory cytokines in animal models of neuropathic pain. When these data are considered together, a unifying hypothesis emerges which implicates a role of central neuroimmune processes in the etiology of neuronal and behavioral hypersensitivity. The present investigation assessed the influence of Propentofylline, a glial modulating and anti-inflammatory agent, on the development of L5 spinal nerve transection-induced hyperalgesia and associated enhancement of spinal neuroimmune responses using real-time reverse transcription–polymerase chain reaction, RNase protection assay, enzyme-linked immunosorbent assay, and immunocytochemistry in rats. The results show that chronic Propentofylline treatment attenuated the development of hyperalgesia and restored the analgesic activity of acute morphine in neuropathic rats. These findings directly correlated with the ability of Propentofylline to inhibit glial activation and enhanced spinal proinflammatory cytokines following peripheral nerve injury. These findings along with our earlier observations of an anti-allodynic activity of Propentofylline using the identical animal model of mononeuropathy supports the concept that modulation of glial and neuroimmune activation may be potential therapeutic targets to treat or prevent neuropathic pain. Further, restoration of the analgesic activity of morphine by Propentofylline treatment suggests that increased glial activity and proinflammatory cytokine responses may account for the decreased analgesic efficacy of morphine observed in the treatment of neuropathic pain.
Bertil B Fredholm - One of the best experts on this subject based on the ideXlab platform.
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Propentofylline and other adenosine transport inhibitors increase the efflux of adenosine following electrical or metabolic stimulation of rat hippocampal slices
Journal of Neurochemistry, 2002Co-Authors: Bertil B Fredholm, Karin Lindstrom, Agneta WallmanjohanssonAbstract:: Propentofylline is a novel neuroprotective agent that has been shown to act as an adenosine transport inhibitor as well as an adenosine receptor antagonist. In the present series of experiments we have compared the effects of Propentofylline with those of known adenosine transport inhibitors and receptor antagonists on the formation of adenosine in rat hippocampal slices. The ATP stores were labeled by incubating the slices with [3H]adenine. The total 3H overflow and the overflow of endogenous and 3H-labeled adenosine, inosine, and hypoxanthine were measured. Adenosine release, secondary to ATP breakdown, was induced both by hypoxia/hypoglycemia and by electrical field stimulation. Propentofylline (20-500 microM) increased the release of endogenous and radiolabeled adenosine, without increasing the total release of purines. Thus, the drug altered the pattern of released purines, i.e., increasing adenosine and decreasing inosine and hypoxanthine. This pattern, which was observed when purine release was induced both by electrical field stimulation and by hypoxia/hypoglycemia, was shared by the nucleoside transport inhibitor dipyridamole (1 microM) and by mioflazine (1 microM) and nitrobenzylthioinosine (1 microM). By contrast, other xanthines, including theophylline (100 microM) and 8-cyclopentyltheophylline (10 microM), enprofylline (100 microM), or torbafylline (300 microM), if anything, increased the total release of purines without alterations of the pattern of release. These results indicate that nucleoside transport inhibitors can decrease the release of purines from cells and at the same time increase the concentration of extracellular adenosine, possibly by preventing its uptake and subsequent metabolism. This change in purine metabolism may be beneficial with regard to cell damage after ischemia. The results also indicate that Propentofylline behaves in such a potentially beneficial manner.
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Propentofylline inhibits polymorphonuclear leukocyte recruitment in vivo by a mechanism involving adenosine a2a receptors
European Journal of Pharmacology, 1996Co-Authors: Yu Zhang, J Raud, Per Hedqvist, Bertil B FredholmAbstract:Abstract Propentofylline is an atypical xanthine derivative that blocks adenosine uptake and has been shown to protect against ischemia-induced cerebral damage. We have studied the effect of Propentofylline on recruitment of polymorphonuclear leukocytes during acute peritonitis induced by zymosan in mice. Following i.p. injection of zymosan, recruitment of polymorphonuclear leukocytes, reflected by myeloperoxidase activity in the peritoneal cavity, increased from 2 h onwards, peaked at 4 h and then decreased gradually. Propentofylline antagonized the zymosan-induced peritoneal myeloperoxidase accumulation in a concentration-dependent manner. This effect of Propentofylline was counteracted by the non-selective adenosine receptor antagonist theophylline (50 mg/kg), and by the selective adenosine A2A receptor antagonists, 4-amino-8-chloro-1-phenyl-[1,2,4]-triazolo[4,3-a]quinoxaline (CP 66713) and 1,3-dipropyl-8-[3,4-dimethoxystyryl]-7-methylxanthine (KF 17387) (both at 2 mg/kg). The results indicate that Propentofylline can reduce polymorphonuclear leukocyte recruitment in vivo and that this effect is related to an action on adenosine A2A receptors.
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Propentofylline enhancement of the actions of adenosine on neutrophil leukocytes
Biochemical Pharmacology, 1994Co-Authors: Yu Zhang, Bertil B FredholmAbstract:Abstract In agreement with previous results, activation of adenosine A 2 receptors was found to inhibit the exocytotic release of elastase and the oxidative burst induced by formyl-MetLeuPhe (fMLP) in human neutrophils. The adenosine analogue 5′- N -ethycarboxamidoadenosine (NECA) was more potent than adenosine (IC 50 14 vs 64 nM). The effects of adenosine and NECA were not influenced by the A 1 -adenosine receptor selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 300 nM), but were abolished by the non-selective adenosine receptor antagonist 9-chloro-2-(2-furanyl)- 5,6-dihydro-[1,2,4]-triazolo [1,5]quinazolin-5-imine monomethanesulfonate (CGS 15943; 10 μM). Propentofylline per se caused a concentration-dependent inhibition of H 2 O 2 production. At 100 μM, Propentofylline significantly enhanced the effect of adenosine, but not that of NECA. This effect of Propentofylline was shared by the known uptake inhibitor dipyridamole. Neither adenosine nor Propentofylline altered fMLP-induced inositol-(1,4,5)-triphosphate (IP 3 ) formation. The results demonstrate that Propentofylline can counteract neutrophil activation, at least partly by enhancing the action of adenosine through blocking its removal, and that the effect is exerted at a step after the initial receptor events.
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Propentofylline a nucleoside transport inhibitor with neuroprotective effects in cerebral ischemia
General Pharmacology-the Vascular System, 1994Co-Authors: Fiona E Parkinson, Karl Rudolphi, Bertil B FredholmAbstract:1. Adenosine is an endogenous neuroprotective agent; stimulation of A1 receptors decreases excitatory amino acid neurotransmission and stimulation of A2 receptors inhibits platelet and neutrophil activation and promotes vasodilation. 2. Post-ischemic administration of Propentofylline (HWA 285) reduces neuronal damage in gerbils and improves glucose metabolism in all regions of brain in acute stroke patients. 3. Propentofylline inhibits the transport of adenosine into cultured cells and increases extracellular adenosine concentrations in ischemic brain. Thus, enhanced stimulation of adenosine receptors may account for some of the neuroprotective effects of this compound. 4. Propentofylline inhibits free radical production by cultivated microglia cells, stimulates nerve growth factor production and inhibits cAMP-phosphodiesterase activity. These effects may also be important for neuroprotection.
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further evidence that Propentofylline hwa 285 influences both adenosine receptors and adenosine transport
Fundamental & Clinical Pharmacology, 1992Co-Authors: Bertil B Fredholm, J Fastbom, Anders Kvanta, Par Gerwins, F ParkinsonAbstract:: We have examined the actions of a novel xanthine derivative, Propentofylline (HWA 285), that has been shown to protect against ischemic brain damage in rats and gerbils, on adenosine receptors (A1 and A2), and on adenosine transporters using several techniques, cells and tissues. Propentofylline and its hydroxylated metabolite A 72 0287 were about 20 times less potent than theophylline in displacing A1-agonist binding to membranes from rat cortex, and A1-antagonist binding to whole DDT, MF-2 smooth muscle cells. A1-agonist binding to adenosine A1-receptors in several brain structures was inhibited in a concentration-dependent manner by A 72 0287 and Propentofylline as judged by quantitative autoradiography (IC50-values 300-600 microM in eg striatum and in cortex layer IV). In two functional assays, A1-receptor mediated effects were blocked by Propentofylline. A1-receptor-mediated inhibition of cyclic AMP accumulation was virtually abolished by 100 microM Propentofylline. The A1-receptor-mediated inhibition of evoked acetylcholine release was also reduced by Propentofylline, but in this case the effect is not due exclusively to adenosine receptor antagonism but also to another action since the presynaptic inhibitory effect of carbachol was also inhibited. Adenosine A2-receptors were also antagonized by Propentofylline as judged by a concentration-dependent antagonism of A2-agonist-induced cAMP accumulation in human T-leukemia cells (possessing putative A2b-receptors; pA2-value 180 microM compared to 0.26 microM for 8-cpt), and in PC-12 cells (possessing putative A2a-receptors, Ki-value 365 microM). Finally, adenosine transporters were affected by Propentofylline and A 72 0287. Thus, [3H]-nitrobenzylthioinosine-binding to guinea-pig cardiac membranes was blocked by Propentofylline or A 72 0287 (Ki 270 microM). The present results show that Propentofylline and its hydroxylated metabolite can influence adenosine mechanisms in a multitude of ways. How these different actions may contribute to the ability of Propentofylline to reduce the magnitude of ischemic damage is discussed.
Flobert Y Tanga - One of the best experts on this subject based on the ideXlab platform.
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attenuation of morphine tolerance withdrawal induced hyperalgesia and associated spinal inflammatory immune responses by Propentofylline in rats
Neuropsychopharmacology, 2004Co-Authors: Vasudeva Raghavendra, Flobert Y Tanga, Joyce A DeleoAbstract:Attenuation of Morphine Tolerance, Withdrawal-Induced Hyperalgesia, and Associated Spinal Inflammatory Immune Responses by Propentofylline in Rats
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Attenuation of Morphine Tolerance, Withdrawal-Induced Hyperalgesia, and Associated Spinal Inflammatory Immune Responses by Propentofylline in Rats
Neuropsychopharmacology, 2004Co-Authors: Vasudeva Raghavendra, Flobert Y Tanga, Joyce A DeleoAbstract:The activation of glial cells and enhanced proinflammatory cytokine expression at the spinal cord has been implicated in the development of morphine tolerance, and morphine withdrawal-induced hyperalgesia. The present study investigated the effect of Propentofylline, a glial modulator, on the expression of analgesic tolerance and withdrawal-induced hyperalgesia in chronic morphine-treated rats. Chronic morphine administration through repeated subcutaneous injection induced glial activation and enhanced proinflammatory cytokine levels at the lumbar spinal cord. Moreover, glial activation and enhanced proinflammatory cytokine levels exhibited a temporal correlation with the expression of morphine tolerance and hyperalgesia. Consistently, Propentofylline attenuated the development of hyperalgesia and the expression of spinal analgesic tolerance to morphine. The administration of Propentofylline during the induction of morphine tolerance also attenuated glial activation and proinflammatory cytokines at the L5 lumbar spinal cord. These results further support the hypothesis that spinal glia and proinflammatory cytokines contribute to the mechanisms of morphine tolerance and associated abnormal pain sensitivity.
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anti hyperalgesic and morphine sparing actions of Propentofylline following peripheral nerve injury in rats mechanistic implications of spinal glia and proinflammatory cytokines
Pain, 2003Co-Authors: Vasudeva Raghavendra, Flobert Y Tanga, Maria D Rutkowski, Joyce A DeleoAbstract:Abstract Injury to peripheral nerves often produces non-physiological, long-lasting spontaneous pain, hyperalgesia and allodynia that are refractory to standard treatment and often insensitive to opioids, such as morphine. Recent studies demonstrate spinal glial activation and increased proinflammatory cytokines in animal models of neuropathic pain. When these data are considered together, a unifying hypothesis emerges which implicates a role of central neuroimmune processes in the etiology of neuronal and behavioral hypersensitivity. The present investigation assessed the influence of Propentofylline, a glial modulating and anti-inflammatory agent, on the development of L5 spinal nerve transection-induced hyperalgesia and associated enhancement of spinal neuroimmune responses using real-time reverse transcription–polymerase chain reaction, RNase protection assay, enzyme-linked immunosorbent assay, and immunocytochemistry in rats. The results show that chronic Propentofylline treatment attenuated the development of hyperalgesia and restored the analgesic activity of acute morphine in neuropathic rats. These findings directly correlated with the ability of Propentofylline to inhibit glial activation and enhanced spinal proinflammatory cytokines following peripheral nerve injury. These findings along with our earlier observations of an anti-allodynic activity of Propentofylline using the identical animal model of mononeuropathy supports the concept that modulation of glial and neuroimmune activation may be potential therapeutic targets to treat or prevent neuropathic pain. Further, restoration of the analgesic activity of morphine by Propentofylline treatment suggests that increased glial activity and proinflammatory cytokine responses may account for the decreased analgesic efficacy of morphine observed in the treatment of neuropathic pain.
Wolfdieter Heiss - One of the best experts on this subject based on the ideXlab platform.
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Propentofylline improves regional cerebral glucose metabolism and neuropsychologic performance in vascular dementia
Journal of the Neurological Sciences, 1996Co-Authors: Rudiger Mielke, B Kittner, M Ghaemi, Josef Kessler, B Szelies, Karl Herholz, Wolfdieter HeissAbstract:Abstract In a double-blind, placebo-controlled trial in thirty patients with mild to moderate vascular dementia (VD) according to DSM-III-R criteria, the effects of the adenosine uptake blocker Propentofylline (HWA 285) on regional cerebral glucose metabolism (rCMRG1) was studied using positron emission tomography of 2-[ 18 F]fluoro-2-deoxy- d -glucose (FDG). 25 subjects completed the 3-months study. Propentofylline significantly improved relative rCMRGl in the motor cortex, while relative rCMRG1 in the placebo treated group worsened significantly. Neuropsychologically, visual information processing was improved in the Propentofylline group and we observed a trend towards a slowing of the progression of cognitive deterioration in patients with VD. The results of the longitudinal analysis showed further that neuropsychological and metabolic changes are closely related. These findings justify a large-scale clinical trial to prove therapeutic efficacy.
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effect of Propentofylline on regional cerebral glucose metabolism in acute ischemic stroke
Journal of Cerebral Blood Flow and Metabolism, 1993Co-Authors: Michael Huber, B Kittner, C Hojer, Gereon R Fink, M Neveling, Wolfdieter HeissAbstract:In a randomized double-blind placebo-controlled study in 30 patients with acute ischemic stroke, the effect of the adenosine uptake blocker Propentofylline on regional brain glucose metabolism (rCMRglu) was investigated using repeated positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-d-glucose (FDG). Treatment was initiated within 48 h after onset of symptoms. The clinical course was followed for 3 months. In the Propentofylline group, after 14 days rCMRglu was increased in the infarct by 37.3% and was practically unchanged in other brain regions, whereas in the control group glucose metabolism had decreased in all regions (1.4–13.4%). These differences were significant between the two groups [Analysis of variance (ANOVA) p = 0.005]. Although there was a trend toward greater clinical improvement in the Propentofylline-treated patients, this did not reach statistical significance. The results correspond to experimental data showing that Propentofylline improves energy metabolism in cerebral isc...
