The Experts below are selected from a list of 1221 Experts worldwide ranked by ideXlab platform
Robert Vink - One of the best experts on this subject based on the ideXlab platform.
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the effect of an nk1 Receptor Antagonist on blood spinal cord barrier permeability following balloon compression induced spinal cord injury
Acta Neurochirurgica, 2013Co-Authors: Anna V Leonard, Robert VinkAbstract:The blood spinal cord barrier (BSCB) is disrupted following spinal cord injury (SCI) resulting in vasogenic edema and increased intrathecal pressure (ITP). The neuropeptide substance P (SP) has been implicated in the development of blood–brain barrier (BBB) disruption, edema, and increased intracranial pressure following brain injury, although it has not been investigated in SCI. The balloon compression model of experimental SCI has many advantages in that it replicates the “closed” environment observed clinically. Accordingly, this study characterized whether this model produces an increase in BSCB permeability and edema, and whether a SP, NK1 Tachykinin Receptor Antagonist, N-acetyl-l-tryptophan (NAT) reduces such BSCB disruption and edema formation. At 30 min post-injury, animals were administered 2.5 mg/kg NAT or saline. Subgroups of animals were assessed for BSCB permeability (Evan’s Blue) and spinal cord edema (wet weight/dry weight). BSCB permeability and edema were significantly increased in injured groups compared with sham (p < 0.001). There was no significant difference between vehicle and NAT treatment. We conclude that the balloon compression model of SCI produces significant BSCB disruption although NAT treatment did not attenuate BSCB permeability or edema. Further studies are required to fully elucidate the role of SP following SCI.
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combined tissue plasminogen activator and an nk1 Tachykinin Receptor Antagonist an effective treatment for reperfusion injury following acute ischemic stroke in rats
Neuroscience, 2012Co-Authors: Renée J. Turner, Robert VinkAbstract:Abstract We have recently reported on the efficacy of an NK1 Tachykinin Receptor Antagonist in improving outcome following stroke, including reduced blood–brain barrier (BBB) disruption, reduced cerebral edema and improved functional outcome. The clinically approved stroke treatment, tissue plasminogen activator (tPA), has been associated with an increased risk of hemorrhage and death, if given at later time points. Accordingly, adjunctive therapies have been investigated to reduce the adverse effects of tPA and improve outcome. The aim of the present study was to characterize the effects of a combination of an NK1 Tachykinin Receptor Antagonist with tPA, on BBB permeability and functional outcome following transient ischemic stroke in rats. Stroke was induced in male Sprague–Dawley rats using a reversible thread model of middle cerebral artery occlusion where occlusion was maintained for 2 h, followed by reperfusion. Animals received either 25 mg/kg of N-acetyl- l -tryptophan or 1 mg/kg of tPA, either alone or in combination, or equal volume saline vehicle, intravenously at the time of reperfusion. Functional outcome was assessed by the rotarod, bilateral asymmetry test, modified neuroscore and open field tests. BBB permeability was assessed by Evans Blue extravasation. Combination therapy of an NK1 Tachykinin Receptor Antagonist with tPA significantly reduced BBB permeability, functional deficits and the incidence of intracerebral hemorrhage and death. As such, combined tPA–NK1 Tachykinin Receptor Antagonist treatment may represent a novel therapeutic intervention for the treatment of reperfusion injury in acute ischemic stroke.
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a substance p Antagonist improves outcome when administered 4 h after onset of ischaemic stroke
Brain Research, 2011Co-Authors: Renée J. Turner, Stephen C Helps, Emma Thornton, Robert VinkAbstract:Previous studies have suggested that substance P (SP) plays a critical role in the development of brain oedema and functional deficits following traumatic brain injury and that SP Receptor antagonism may improve outcome. No studies have described such a role in ischemic stroke. The present study characterized the effects of the NK1 Tachykinin Receptor Antagonist, n-acetyl-L-tryptophan (NAT), on blood-brain barrier (BBB) breakdown, oedema formation, infarct volume and functional outcome following reversible ischemic stroke in rats. Ischemia was induced using a reversible thread model of middle cerebral artery occlusion where occlusion was maintained for 2 h before reperfusion. Animals received either NAT or equal volume saline vehicle intravenously at 2 h post-reperfusion. Ischaemic stroke resulted in increased perivascular SP immunoreactivity at 24 h. Administration of NAT significantly reduced oedema formation and BBB permeability at 24 h post-ischemia and significantly improved functional outcome as assessed over 7 days. There was no effect on infarct volume. We conclude that inhibition of SP activity with a NK1 Tachykinin Receptor Antagonist is effective in reducing cerebral oedema, BBB permeability and functional deficits following reversible ischemia and may therefore represent a novel therapeutic approach to the treatment of ischaemic stroke.
Renée J. Turner - One of the best experts on this subject based on the ideXlab platform.
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combined tissue plasminogen activator and an nk1 Tachykinin Receptor Antagonist an effective treatment for reperfusion injury following acute ischemic stroke in rats
Neuroscience, 2012Co-Authors: Renée J. Turner, Robert VinkAbstract:Abstract We have recently reported on the efficacy of an NK1 Tachykinin Receptor Antagonist in improving outcome following stroke, including reduced blood–brain barrier (BBB) disruption, reduced cerebral edema and improved functional outcome. The clinically approved stroke treatment, tissue plasminogen activator (tPA), has been associated with an increased risk of hemorrhage and death, if given at later time points. Accordingly, adjunctive therapies have been investigated to reduce the adverse effects of tPA and improve outcome. The aim of the present study was to characterize the effects of a combination of an NK1 Tachykinin Receptor Antagonist with tPA, on BBB permeability and functional outcome following transient ischemic stroke in rats. Stroke was induced in male Sprague–Dawley rats using a reversible thread model of middle cerebral artery occlusion where occlusion was maintained for 2 h, followed by reperfusion. Animals received either 25 mg/kg of N-acetyl- l -tryptophan or 1 mg/kg of tPA, either alone or in combination, or equal volume saline vehicle, intravenously at the time of reperfusion. Functional outcome was assessed by the rotarod, bilateral asymmetry test, modified neuroscore and open field tests. BBB permeability was assessed by Evans Blue extravasation. Combination therapy of an NK1 Tachykinin Receptor Antagonist with tPA significantly reduced BBB permeability, functional deficits and the incidence of intracerebral hemorrhage and death. As such, combined tPA–NK1 Tachykinin Receptor Antagonist treatment may represent a novel therapeutic intervention for the treatment of reperfusion injury in acute ischemic stroke.
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a substance p Antagonist improves outcome when administered 4 h after onset of ischaemic stroke
Brain Research, 2011Co-Authors: Renée J. Turner, Stephen C Helps, Emma Thornton, Robert VinkAbstract:Previous studies have suggested that substance P (SP) plays a critical role in the development of brain oedema and functional deficits following traumatic brain injury and that SP Receptor antagonism may improve outcome. No studies have described such a role in ischemic stroke. The present study characterized the effects of the NK1 Tachykinin Receptor Antagonist, n-acetyl-L-tryptophan (NAT), on blood-brain barrier (BBB) breakdown, oedema formation, infarct volume and functional outcome following reversible ischemic stroke in rats. Ischemia was induced using a reversible thread model of middle cerebral artery occlusion where occlusion was maintained for 2 h before reperfusion. Animals received either NAT or equal volume saline vehicle intravenously at 2 h post-reperfusion. Ischaemic stroke resulted in increased perivascular SP immunoreactivity at 24 h. Administration of NAT significantly reduced oedema formation and BBB permeability at 24 h post-ischemia and significantly improved functional outcome as assessed over 7 days. There was no effect on infarct volume. We conclude that inhibition of SP activity with a NK1 Tachykinin Receptor Antagonist is effective in reducing cerebral oedema, BBB permeability and functional deficits following reversible ischemia and may therefore represent a novel therapeutic approach to the treatment of ischaemic stroke.
Loris A. Chahl - One of the best experts on this subject based on the ideXlab platform.
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localization of fos like immunoreactivity induced by the nk3 Tachykinin Receptor agonist senktide in the guinea pig brain
British Journal of Pharmacology, 1997Co-Authors: Jane Yip, Loris A. ChahlAbstract:1. The effects of intracerebroventricular (i.c.v.) administration of the NK3 Tachykinin Receptor agonist, senktide (10 nmol each side), in guinea-pigs pretreated with the selective NK3 Tachykinin Receptor Antagonist, SR142801 (3 mg kg(-1) subcutaneous, s.c., 30 min before senktide), or its less active enantiomer, SR142806 (3 mg kg(-1) s.c. 30 min before senktide), on behaviour and on the distribution of Fos-like immunoreactivity (Fos-LI) in central neurones were investigated. Guinea-pigs were chosen for the study since they possess NK3 Tachykinin Receptors with pharmacological characteristics similar to those in man. 2. Wet-dog shakes, but not locomotor activity, elicited by senktide i.c.v. were significantly reduced by SR142801 but not by SR142806, confirming the involvement of NK3 Tachykinin Receptors in wet-dog shake behaviour. 3. Senktide induced increased numbers of Fos-LI neurones in the following brain areas: frontal, parietal and piriform cortex, the lateral septum, the CA1, CA2, subiculum and dentate gyrus of the hippocampus, most areas in the amygdala, thalamus and hypothalamus, medial geniculate nucleus and the ventral cochlear nucleus. Pretreatment with SR142801, but not with SR142806, before administration of senktide inhibited Fos-LI expression in the cingulate cortex, dentate gyrus of the hippocampus, some regions of the thalamus, hypothalamus and amygdala and the ventral cochlear nucleus. 4. The present results are the first demonstration that senktide induces Fos-LI in widespread areas of the guinea-pig brain. It is proposed that NK3 Tachykinin Receptors may play a more extensive role in the control of diverse brain functions, including cortical processing, learning and memory, neuroendocrine and behavioural regulation, than is currently recognized.
Jane Yip - One of the best experts on this subject based on the ideXlab platform.
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localization of fos like immunoreactivity induced by the nk3 Tachykinin Receptor agonist senktide in the guinea pig brain
British Journal of Pharmacology, 1997Co-Authors: Jane Yip, Loris A. ChahlAbstract:1. The effects of intracerebroventricular (i.c.v.) administration of the NK3 Tachykinin Receptor agonist, senktide (10 nmol each side), in guinea-pigs pretreated with the selective NK3 Tachykinin Receptor Antagonist, SR142801 (3 mg kg(-1) subcutaneous, s.c., 30 min before senktide), or its less active enantiomer, SR142806 (3 mg kg(-1) s.c. 30 min before senktide), on behaviour and on the distribution of Fos-like immunoreactivity (Fos-LI) in central neurones were investigated. Guinea-pigs were chosen for the study since they possess NK3 Tachykinin Receptors with pharmacological characteristics similar to those in man. 2. Wet-dog shakes, but not locomotor activity, elicited by senktide i.c.v. were significantly reduced by SR142801 but not by SR142806, confirming the involvement of NK3 Tachykinin Receptors in wet-dog shake behaviour. 3. Senktide induced increased numbers of Fos-LI neurones in the following brain areas: frontal, parietal and piriform cortex, the lateral septum, the CA1, CA2, subiculum and dentate gyrus of the hippocampus, most areas in the amygdala, thalamus and hypothalamus, medial geniculate nucleus and the ventral cochlear nucleus. Pretreatment with SR142801, but not with SR142806, before administration of senktide inhibited Fos-LI expression in the cingulate cortex, dentate gyrus of the hippocampus, some regions of the thalamus, hypothalamus and amygdala and the ventral cochlear nucleus. 4. The present results are the first demonstration that senktide induces Fos-LI in widespread areas of the guinea-pig brain. It is proposed that NK3 Tachykinin Receptors may play a more extensive role in the control of diverse brain functions, including cortical processing, learning and memory, neuroendocrine and behavioural regulation, than is currently recognized.
Pierangelo Geppetti - One of the best experts on this subject based on the ideXlab platform.
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plasma extravasation in the rat trachea induced by cold air is mediated by Tachykinin release from sensory nerves
American Journal of Respiratory and Critical Care Medicine, 1995Co-Authors: Shigemi Yoshihara, Isao Yamawaki, Pierangelo Geppetti, Brendan Chan, Fabio Luigi Massimo Ricciardolo, Pierre P Massion, Jay A. NadelAbstract:Cold air was delivered to anesthetized, artificially ventilated, pathogen-free F344 rats via a tracheal cannula. Inhalation of cold air increased Evans blue dye extravasation in the trachea in a time-dependent (1 to 10 min) manner. Plasma extravasation increased after 3 min exposure to cold air and reached a maximum after 10 min exposure. The neutral endopeptidase inhibitor, phosphoramidon (2.5 mg/kg, intravenously), increased by 84% the plasma extravasation induced by inhalation of cold air for 1 min. The plasma extravasation evoked by 5 min exposure to cold air was abolished by the NK1 Tachykinin Receptor Antagonist, CP-99,994 (4 mg/kg, intravenously); was reduced 30% by the B2 bradykinin Receptor Antagonist, HOE140 (0.1 mumol/kg, intravenously); and was not affected by H1 (pyrilamine, 10 mg/kg, intraperitoneally) or H2 (cimetidine, 10 mg/kg, intraperitoneally) histamine Receptor Antagonists or the cyclooxygenase inhibitor indomethacin (5 mg/kg, intravenously). In rats infected with Sendai virus, plasma...
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role of kinins in the vascular extravasation evoked by antigen and mediated by Tachykinins in guinea pig trachea
Journal of Immunology, 1993Co-Authors: Claude Bertrand, J A Nadel, Isao Yamawaki, Pierangelo GeppettiAbstract:Tachykinins released from sensory nerves mediate, at least in part, the plasma extravasation induced by allergen challenge to the airways of sensitized guinea pigs. We investigated the role of kinins in this activation of sensory nerves. We found that the increase in Evans blue dye extravasation evoked by aerosol of bradykinin (100 microM, 2 min) in the presence of phosphoramidon (2.5 mg/kg, i.v.) was abolished completely by the selective B2 bradykinin Antagonist, HOE 140 (0.1 mumol/kg, i.v.), and was inhibited (60%) by the selective NK1 Tachykinin Receptor Antagonist, CP-96,345 (2 mumol/kg, i.v.). Plasma extravasation evoked by aerosolized substance P (10 microM/kg, 2 min) in presence of phosphoramidon was abolished by CP-96,345, but was not affected by HOE 140. The extravasation of the Evans blue dye evoked by OVA (5%, 2 min) in sensitized guinea pigs was reduced by HOE 140 (45%) when the animals were perfused after 5 min and by 39% when perfusion was performed at 10 min. In the presence of phosphoramidon, the response to OVA at 10 min was reduced by 57% by HOE 140 and by 72% by CP-96,345. The combination of CP-96,345 and HOE 140 did not further increase the inhibition obtained with CP-96,345 alone. The results provide evidence that the activation of sensory nerves that contribute to Ag-evoked plasma extravasation is due to kinin release. The contribution of this cascade of events may be exaggerated in pathophysiologic conditions in which neutral endopeptidase is down-regulated.
