Exogenous administration of PACAP alleviates traumatic brain injury in rats through a mechanism involving the TLR4/MyD88/NF-κB pathway

Journal of Neurotrauma
Shan-Shan MaoYong-Mei Zhang

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is effective in reducing axonal damage associated with traumatic brain injury (TBI), and has immunomodulatory properties. Toll-like receptor 4 (TLR4) is an important mediator of the innate immune response. It significantly contributes to neuroinflammation induced by brain injury. However, it remains unknown whether exogenous PACAP can modulate TBI through the TLR4/adapter protein myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. In this study, we investigated the potential neuroprotective mechanisms of PACAP pretreatment in a weight-drop model of TBI. PACAP38 was microinjected intracerebroventricularly before TBI. Brain samples were extracted from the pericontusional area in the cortex and hippocampus. We found that TBI induced significant upregulation of TLR4, with peak expression occurring 24 h post-trauma, and that pretreatment with PACAP significantly improved motor and cognitive dysfunction, attenuated neuronal apoptosis, and decreased brain edema. Pretreatment with PACAP inhibited upregulation of TLR4 and its downstream signaling molecules MyD88, p-IκB, and NF-κB, and suppressed increases in the levels of the downstream inflamm...Continue Reading

References

Oct 16, 1989·Biochemical and Biophysical Research Communications·A MiyataD H Coy
Oct 1, 1986·Physiology & Behavior·J P Kroon, A L Riley
Jan 4, 2001·Journal of Neuropathology and Experimental Neurology·P GressensP Evrard
Sep 20, 2001·Current Pharmaceutical Design·T Clausen, R Bullock
Jun 4, 2002·Journal of Neurotrauma·Raj K NarayanLorraine Yurkewicz
Jun 28, 2002·Brain Research. Brain Research Reviews·Ronen R Leker, Esther Shohami
Aug 21, 2002·Genome Biology·Myriam A Armant, Matthew J Fenton
May 30, 2003·Biochemical Society Transactions·L A J O'Neill
Jun 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Seija LehnardtTimothy Vartanian
Aug 9, 2003·Critical Reviews in Immunology·Geoffrey B JohnsonJeffrey L Platt
Sep 27, 2003·Epilepsia·John Bruns, W Allen Hauser
Jun 15, 2004·Brain Pathology·Ramesh Raghupathi
Sep 24, 2004·Current Pharmaceutical Design·Anikó Somogyvári-Vigh, Dóra Reglodi
Jan 18, 2005·Journal of Neuroimmunology·Cinthia FarinaEdgar Meinl
May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dae Young JungKyoungho Suk
Sep 17, 2005·Science·Markus W CovertDavid Baltimore
Nov 29, 2005·Acta neurochirurgica·F TagliaferriJ Kraus
Jan 13, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Elzbieta KojroFalk Fahrenholz
Feb 1, 2006·Journal of Neuroscience Research·William J MackE Sander Connolly
Feb 25, 2006·Cell·Shizuo AkiraOsamu Takeuchi
Mar 31, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Elisabeth DeindlWolfgang-Michael Franz
May 12, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kazuhiro TanakaAkemichi Baba
May 30, 2006·Current Pharmaceutical Design·Niklas MarklundTracy K McIntosh
Jun 19, 2007·British Journal of Anaesthesia·C Werner, K Engelhard
Sep 1, 2007·The New England Journal of Medicine·UNKNOWN SAFE Study InvestigatorsShirley Vallance
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·R Bryan Rock, Phillip K Peterson
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Rajagopal N AravalliJames R Lokensgard

❮ Previous
Next ❯

Citations

Mar 21, 2013·Journal of Physiology and Biochemistry·Xia QinYong-Mei Zhang
Jun 9, 2014·Journal of Molecular Neuroscience : MN·Kazuyuki MiyamotoSeiji Shioda
Jan 30, 2015·Frontiers in Molecular Neuroscience·Maria E Figueiredo-PereiraPeter Serrano
May 15, 2018·Headache·Joshua Kamins, Andrew Charles
Jul 23, 2019·Headache·Jonathan M Borkum
Feb 6, 2020·International Journal of Molecular Sciences·Denes TothDora Reglodi
Jul 16, 2020·The Journal of Headache and Pain·Silvia BenemeiUNKNOWN European Headache Federation School of Advanced Studies (EHF-SAS)
Jul 30, 2020·Cellular and Molecular Life Sciences : CMLS·Hauke ThieslerHerbert Hildebrandt
Dec 17, 2018·Molecular Neurobiology·Daniel YoungerNamas Chandra
Feb 6, 2017·Journal of Neuroscience Research·Laura S Moye, Amynah A Pradhan
Jan 28, 2017·International Journal of Inflammation·Manoj Banjara, Chaitali Ghosh
Apr 24, 2020·Current Therapeutic Research, Clinical and Experimental·Li Shan ChiuBruno P Meloni

❮ Previous
Next ❯

Methods Mentioned

BETA
protein assay
ELISA
fluorescence microscopy
enzyme-linked immunosorbent assay
nuclear translocation

Software Mentioned

Glyko Bandscan
Image Pro - Plus

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.