Activation of pdgf-cc

For electron microscopic analysis, sections were examined with a Phillips CM12 transmission electron microscope. Controls using normal rabbit IgG gave only background staining data not shown. For the tPA staining, antigen retrieval with 0. Immunofluorescence localization Details of the immunofluorescence localizations are presented in Supplementary Methods 2 online.

Cell lysates were directly subjected to immunoblotting, and receptor tyrosine phosphorylation was determined using a phosphotyrosine-specific antibody PY99, Santa Cruz. As a loading control immunoblotting of the endoplasmic reticulum integral membrane protein calnexin was also performed sc, Santa Cruz.

Six hours later, animals were perfused with PBS for 4 min and the brains were removed and separated into two hemispheres. Mouse model of ischemic stroke Details of the mouse model of ischemic stroke are presented in Supplementary Methods 1 and in Supplementary Figure 6 online. Animals were then perfused with PBS for 4 min and the brains were removed and separated into hemispheres ipsilateral and contralateral to the MCAO. Acknowledgments We want to thank P. Wang, G. Schielke and D. Lombardi for helpful discussions and critical reading of the manuscript; N.

Gorlatova for surface plasmon resonance analysis; and S. Rezaian and M. Wahl for technical assistance. Strickland ; NS to M. Eriksson and C. Page 9 Reference List 1. Thom T, et al. Circulation ;e85— e Molecular mechanisms of cerebral ischemia-induced neuronal death. Cytol ;— Stroke--tPA and the clinic. Science ; Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature ;— Neurosci ;— Wang YF, et al. Tissue plasminogen activator tPA increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice.

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Blood Flow Metab. Effects of plasminogen activator inhibitor-1 on ischemic brain injury in permanent and thrombotic middle cerebral artery occlusion models in mice. Capdeville, R. Glivec STI, imatinib , a rationally developed, targeted anticancer drug.

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Hao, Z. Gualandris, A. Membrane depolarization induces calcium-dependent secretion of tissue plasminogen activator. Breedveld, P. The effect of Bcrp1 Abcg2 on the in vivo pharmacokinetics and brain penetration of imatinib mesylate Gleevec : implications for the use of breast cancer resistance protein and P -glycoprotein inhibitors to enable the brain penetration of imatinib in patients.

Cancer Res. Melchor, J. Tissue plasminogen activator in central nervous system physiology and pathology. This work was supported by grants from the Thierry Latran Foundation U. R01 NS and Karolinska Institutet. We would like to thank Sofia Wittgren and Mark Warnock for technical assistance. We would also like to thank R. Filipkowski for comments on the manuscript. Electronic supplementary material : The online version of this article doi Supplementary information: Supplementary figures and video are present as Online Resource on the Acta Neuropathologica journal website.

Compliance with ethical standards. Conflict of interest : The authors declare that no conflict of interest exists. National Center for Biotechnology Information , U.

Acta Neuropathol. Author manuscript; available in PMC Mar 1. Sebastian A. Adzemovic , 1 Susanne Nichterwitz , 4 Daniel A. Lawrence , 3 Eva Hedlund , 4 and Ulf Eriksson 1. Milena Z. Daniel A. Author information Copyright and License information Disclaimer. Corresponding author. Lewandowski: es. Copyright notice.

The publisher's final edited version of this article is available at Acta Neuropathol. See other articles in PMC that cite the published article. Abstract Amyotrophic lateral sclerosis ALS is a fatal neurodegenerative disease with unknown origins. Introduction Amyotrophic lateral sclerosis ALS is a rapidly progressing disease where motor neurons in spinal cord and brain degenerate resulting in paralysis and death [ 6 ].

Proteolytic activity of tPA Frozen lumbar spinal cords were homogenised in 0. Experimental design For tissue section analysis e.

Open in a separate window. Discussion The origins of ALS and factors affecting the onset of sporadic forms remain largely unknown. Supplementary Material 1 - Online Video 1 Click here to view. Footnotes Electronic supplementary material : The online version of this article doi Compliance with ethical standards Conflict of interest : The authors declare that no conflict of interest exists. References 1. Imatinib enhances functional outcome after spinal cord injury. PLoS One.

Imatinib ameliorates neuroinflammation in a rat model of multiple sclerosis by enhancing blood-brain barrier integrity and by modulating the peripheral immune response.

Al-Chalabi A, Hardiman O. The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol. Pericytes regulate the blood-brain barrier. Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis.

J Neurochem. The neurobiology of amyotrophic lateral sclerosis. Eur J Neurosci. Onset and progression in inherited ALS determined by motor neurons and microglia. Brown WR. A review of string vessels or collapsed, empty basement membrane tubes. Contact us. Europe PMC requires Javascript to function effectively.

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Eriksson U ,. Lawrence DA. Affiliations 1 author 1. A comment on this article appears in " Imatinib buys time for brain after stroke. Share this article Share with email Share with twitter Share with linkedin Share with facebook. Abstract Thrombolytic treatment of ischemic stroke with tissue plasminogen activator tPA is markedly limited owing to concerns about hemorrhagic complications and the requirement that tPA be administered within 3 h of symptoms. These effects are mediated through activation of PDGF-alpha receptors PDGFR-alpha on perivascular astrocytes, and treatment of mice with the PDGFR-alpha antagonist imatinib after ischemic stroke reduces both cerebrovascular permeability and hemorrhagic complications associated with late administration of thrombolytic tPA.

These data demonstrate that PDGF signaling regulates blood-brain barrier permeability and suggest potential new strategies for stroke treatment. Free full text. Nat Med. Author manuscript; available in PMC Jan PMID: Fredriksson , 2 M. Cale , 1 J. Pietras , 2 K. Mann , 1 M. Yepes , 5 D. Strickland , 3 C. Betsholtz , 4 U. Eriksson , 2 and D.

Lawrence 1. Author information Copyright and License information Disclaimer. Correspondence should be addressed to D. Copyright notice. The publisher's final edited version of this article is available at Nat Med. See other articles in PMC that cite the published article. Associated Data Supplementary Materials 1. Abstract Thrombolytic treatment of ischemic stroke with tissue plasminogen activator tPA is markedly limited due to concerns for hemorrhagic complications and the requirement that tPA be administered within 3 h of symptoms.

Open in a separate window. Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Immunofluorescence localization Details of the immunofluorescence localizations are presented in Supplementary Methods 2 online. Mouse model of ischemic stroke Details of the mouse model of ischemic stroke are presented in Supplementary Methods 1 and in Supplementary Figure 6 online.

Supplementary Material 1 Click here to view. Acknowledgments We want to thank P. Reference List 1. Thom T, et al. Heart disease and stroke statistics update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.

Molecular mechanisms of cerebral ischemia-induced neuronal death.