Hedgehog Pathway–Mediated Vascular Alterations Following Trigeminal Nerve Injury
Autor: | Yves Boucher, Luis Villanueva, Michel Pohl, Annie Mauborgne, Wisam Dieb, Sylvie Bourgoin, Nathan Moreau |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Cyclopamine Vascular permeability Tight Junctions Capillary Permeability Rats Sprague-Dawley 03 medical and health sciences Infraorbital nerve chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Claudin-1 medicine Animals Hedgehog Proteins Claudin-5 General Dentistry Neuroinflammation Reverse Transcriptase Polymerase Chain Reaction business.industry Veratrum Alkaloids Trigeminal Neuralgia Immunohistochemistry Immunity Innate Hedgehog signaling pathway Rats Disease Models Animal 030104 developmental biology medicine.anatomical_structure Microscopy Fluorescence chemistry Anesthesia Neuropathic pain Trigeminal Nerve Injuries Endoneurium business 030217 neurology & neurosurgery |
Zdroj: | Journal of Dental Research. 96:450-457 |
ISSN: | 1544-0591 0022-0345 |
DOI: | 10.1177/0022034516679395 |
Popis: | Whereas neurovascular interactions in spinal neuropathic pain models have been well characterized, little attention has been given to such neurovascular interactions in orofacial neuropathic pain models. This study investigated in male Sprague-Dawley rats the vascular changes following chronic constriction injury (CCI) of the infraorbital nerve (IoN), a broadly validated preclinical model of orofacial neuropathic pain. Following IoN-CCI, an early downregulation of tight junction proteins Claudin-1 and Claudin-5 was observed within the endoneurium and perineurium, associated with increased local accumulation of sodium fluorescein (NaFlu) within the IoN parenchyma, as compared with sham animals. These events were evidence of local blood-nerve barrier disruption and increased vascular permeability. A significant upregulation of immunocytes (CD3, CD11b) and innate immunity (TLR2, TLR4) mRNA markers was also observed, suggestive of increased local inflammation. Finally, a significant downregulation of Hedgehog pathway readouts Patched-1 and Gli-1 was observed within the IoN after CCI and local injections of cyclopamine, a Hedgehog pathway inhibitor, replicated in naïve rats the molecular, vascular, and behavioral changes observed following IoN-CCI. These results suggest a major role of Hedgehog pathway inhibition in mediating local increased endoneurial and perineurial vascular permeability following trigeminal nerve injury, thus facilitating immunocytes infiltration, neuroinflammation development, and neuropathic pain-like aversive behavior. |
Databáze: | OpenAIRE |
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