Neuronal degeneration and iNOS expression in experimental brain contusion following treatment with colchicine, dexamethasone, tirilazad mesylate and nimodipine

Gahm, Caroline; Holmin, Staffan; Rudehill, S.; Mathiesen, Tiit

doi:10.1007/s00701-005-0590-7

Cited by 20 publications

(14 citation statements)

References 165 publications

(241 reference statements)

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“…Furthermore, omega-3 polyunsaturated fatty acids were shown to provide neuroprotection after stroke [32]. Gahm et al showed a significant decrease of degenerated neurons early after trauma linked to nimodipine, but also to colchicine, dexamethasone and tirilazad mesylate [33]. In the same study, the expression of iNOS (inducible nitric oxide synthase) was reduced by nimodipine.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Neuroprotective Impact of Nimodipine on Neuro2a Cells by Means of a Surgery-Like Stress Model

Herzfeld

Strauß

Simmermacher

et al. 2014

IJMS

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Nimodipine is well characterized for the management of SAH (subarachnoid hemorrhage) and has been shown to promote a better outcome and less DIND (delayed ischemic neurological deficits). In rat experiments, enhanced axonal sprouting and higher survival of motoneurons was demonstrated after cutting or crushing the facial nerve by nimodipine. These results were confirmed in clinical trials following vestibular Schwannoma surgery. The mechanism of the protective competence of nimodipine is unknown. Therefore, in this study, we established an in vitro model to examine the survival of Neuro2a cells after different stress stimuli occurring during surgery with or without nimodipine. Nimodipine significantly decreased ethanol-induced cell death of cells up to approximately 9% in all tested concentrations. Heat-induced cell death was diminished by approximately 2.5% by nimodipine. Cell death induced by mechanical treatment was reduced up to 15% by nimodipine. Our findings indicate that nimodipine rescues Neuro2a cells faintly, but significantly, from ethanol-, heat- and mechanically-induced cell death to different extents in a dosage-dependent manner. This model seems suitable for further investigation of the molecular mechanisms involved in the neuroprotective signal pathways influenced by nimodipine.

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Section: Discussionmentioning

confidence: 99%

Investigation of the Neuroprotective Impact of Nimodipine on Neuro2a Cells by Means of a Surgery-Like Stress Model

Herzfeld

Strauß

Simmermacher

et al. 2014

IJMS

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“…Morphological identification and quantification of iNOS in DAB staining and immunofluorescence was performed according to our earlier studies [14,15,16,17]. The amount of positive cells was determined manually in the ROI by the same assessor in 400× magnification using a Leica DMRB and a DM400B microscope equipped with a DFC320 camera.…”

Section: Quantificationmentioning

confidence: 99%

iNOS-mediated secondary inflammatory response differs between rat strains following experimental brain contusion

et al. 2012

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Two inbred rat strains with genetically determined differences in susceptibility to develop autoimmune disease displayed different levels of the inflammatory and anti-inflammatory mediators iNOS and MnSOD, indicating genetic regulation. Interestingly, the increased levels of iNOS did not lead to elevated expression of the neuronal cell-death marker fluoro-jade. The increased iNOS expression was correlated with increased expression of superoxide scavenger MnSOD. Excessive peroxynitrite formation was probably prevented by limitation of available superoxide. Subsequently, the higher expression of potentially deleterious iNOS in PVGa did not result in increased neuronal death.

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“…65 The acute and long-lasting excessive quantities of NO release post-TBI are generated from iNOS and far outweigh the increases in eNOS and nNOS. [66][67][68] In vivo and in culture, iNOS was shown to augment the release of CGRP from trigeminal afferents. 69,70 However, considering the evidence for nNOS in migraine, as well as inflammatory pain studies, 26,71 it is reasonable to expect nNOS involvement in the pain pathway post-TBI.…”

Section: Trauma-induced Pain Signaling Molecules and Their Modulationmentioning

confidence: 99%

Trigeminal Pain Molecules, Allodynia, and Photosensitivity Are Pharmacologically and Genetically Modulated in a Model of Traumatic Brain Injury

Daiutolo

Tyburski

Clark

et al. 2016

Journal of Neurotrauma

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The pain-signaling molecules, nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP), are implicated in the pathophysiology of post-traumatic headache (PTH) as they are for migraine. This study assessed the changes of inducible NOS (iNOS) and its cellular source in the trigeminal pain circuit, as well as the relationship between iNOS and CGRP after controlled cortical impact (CCI) injury in mice. The effects of a CGRP antagonist (MK8825) and sumatriptan on iNOS messenger RNA (mRNA) and protein were compared to vehicle at 2 weeks postinjury. Changes in CGRP levels in the trigeminal nucleus caudalis (TNC) in iNOS knockouts with CCI were compared to wild-type (WT) mice at 3 days and 2 weeks post injury. Trigeminal allodynia and photosensitivity were measured. MK8825 and sumatriptan increased allodynic thresholds in CCI groups compared to vehicle ( p < 0.01), whereas iNOS knockouts were not different from WT. Photosensitivity was attenuated in MK8825 mice and iNOS knockouts compared to WT ( p < 0.05). MK8825 and sumatriptan reduced levels of iNOS mRNA and iNOS immunoreactivity in the TNC and ganglia ( p < 0.01). Differences in iNOS cellular localization were found between the trigeminal ganglia and TNC. Although the knockout of iNOS attenuated CGRP at 3 days ( p < 0.05), it did not reduce CGRP at 2 weeks. CGRP immunoreactivity was found in the meningeal layers post-CCI, while negligible in controls. Findings support the importance of interactions between CGRP and iNOS in mediating allodynia, as well as the individual roles in photosensitivity. Mitigating prolonged increases in CGRP may be a promising intervention for treating acute PTH.

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Neuronal degeneration and iNOS expression in experimental brain contusion following treatment with colchicine, dexamethasone, tirilazad mesylate and nimodipine

Cited by 20 publications

References 165 publications

Investigation of the Neuroprotective Impact of Nimodipine on Neuro2a Cells by Means of a Surgery-Like Stress Model

Investigation of the Neuroprotective Impact of Nimodipine on Neuro2a Cells by Means of a Surgery-Like Stress Model

iNOS-mediated secondary inflammatory response differs between rat strains following experimental brain contusion

Trigeminal Pain Molecules, Allodynia, and Photosensitivity Are Pharmacologically and Genetically Modulated in a Model of Traumatic Brain Injury

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