{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:10:32Z","timestamp":1780657832666,"version":"3.54.1"},"reference-count":87,"publisher":"IOP Publishing","issue":"2","license":[{"start":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T00:00:00Z","timestamp":1588032000000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/iop-standard\/v1"},{"start":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T00:00:00Z","timestamp":1588032000000},"content-version":"tdm","delay-in-days":27,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["UL1TR002736"],"award-info":[{"award-number":["UL1TR002736"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"crossref","award":["R01DC01379801"],"award-info":[{"award-number":["R01DC01379801"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1DP2EB022357"],"award-info":[{"award-number":["1DP2EB022357"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["J. Neural Eng."],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Objective.<\/jats:italic>\n                    Neuroprosthetics hold tremendous promise to restore function through brain-computer interfaced devices. However, clinical applications of implantable microelectrodes remain limited given the challenges of maintaining neuronal signals for extended periods of time and with multiple biological mechanisms negatively affecting electrode performance. Acute and chronic inflammation, oxidative stress, and blood brain barrier disruption contribute to inconsistent electrode performance. We hypothesized that therapeutic hypothermia (TH) applied at the microelectrode insertion site will positively modulate both inflammatory and apoptotic pathways, promoting neuroprotection and improved performance in the long-term.\n                    <jats:italic>Approach.<\/jats:italic>\n                    A custom device and thermoelectric system were designed to deliver controlled TH locally to the cortical implant site at the time of microelectrode array insertion and immediately following surgery. The TH paradigm was derived from\n                    <jats:italic>in vivo<\/jats:italic>\n                    cortical temperature measurements and finite element modeling of temperature distribution profiles in the cortex. Male Sprague-Dawley rats were implanted with non-functional Utah microelectrodes arrays (UMEA) consisting of 4 \u00d7 4 grid of 1.5 mm long parylene-coated silicon shanks. In one group, TH was applied to the implant site for two hours following the UMEA implantation, while the other group was implanted under normothermic conditions without treatment. At 48 h, 72 h, 7 d and 14 d post-implantation, mRNA expression levels for genes associated with inflammation and apoptosis were compared between normothermic and hypothermia-treated groups.\n                    <jats:italic>Main results.<\/jats:italic>\n                    The custom system delivered controlled TH to the cortical implant site and the numerical models confirmed that the temperature decrease was confined locally. Furthermore, a one-time application of TH post UMEA insertion significantly reduced the acute inflammatory response with a reduction in the expression of inflammatory regulating cytokines and chemokines.\n                    <jats:italic>Significance.<\/jats:italic>\n                    This work provides evidence that acutely applied hypothermia is effective in significantly reducing acute inflammation post intracortical electrode implantation.\n                  <\/jats:p>","DOI":"10.1088\/1741-2552\/ab85d2","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T18:15:14Z","timestamp":1585851314000},"page":"026035","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Therapeutic hypothermia reduces cortical inflammation associated with utah array implants"],"prefix":"10.1088","volume":"17","author":[{"given":"Elizabeth A","family":"Dugan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassie","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilmar","family":"Tamames","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W Dalton","family":"Dietrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis S","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9586-9400","authenticated-orcid":false,"given":"Abhishek","family":"Prasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5953-8516","authenticated-orcid":false,"given":"Suhrud M","family":"Rajguru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2020,4,28]]},"reference":[{"key":"jneab85d2bib1","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1109\/TNSRE.2017.2677443","type":"journal-article","article-title":"Review: human intracortical recording and neural decoding for brain-computer interfaces","volume":"25","author":"Brandman","year":"2017","journal-title":"IEEE Trans. Neural Syst. Rehabil. Eng."},{"key":"jneab85d2bib2","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1038\/nm.3953","type":"journal-article","article-title":"Clinical translation of a high-performance neural prosthesis","volume":"21","author":"Gilja","year":"2015","journal-title":"Nat. Med."},{"key":"jneab85d2bib3","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/nature11076","type":"journal-article","article-title":"Reach and grasp by people with tetraplegia using a neurally controlled robotic arm","volume":"485","author":"Hochberg","year":"2012","journal-title":"Nature"},{"key":"jneab85d2bib4","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1146\/annurev-bioeng-071910-124640","type":"journal-article","article-title":"Sensors and decoding for intracortical brain computer interfaces","volume":"15","author":"Homer","year":"2013","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"jneab85d2bib5","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1615\/CritRevBiomedEng.2018027166","type":"journal-article","article-title":"Understanding the role of innate immunity in the response to intracortical microelectrodes","volume":"46","author":"Hermann","year":"2018","journal-title":"Crit Rev. Biomed. Eng."},{"key":"jneab85d2bib6","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2560\/10\/6\/066014","type":"journal-article","article-title":"Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates","volume":"10","author":"Barrese","year":"2013","journal-title":"J. Neural. Eng."},{"key":"jneab85d2bib7","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3389\/fneng.2014.00002","type":"journal-article","article-title":"Abiotic-biotic characterization of Pt\/Ir microelectrode arrays in chronic implants","volume":"7","author":"Prasad","year":"2014","journal-title":"Front Neuroeng."},{"key":"jneab85d2bib8","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1097\/00004647-200003000-00012","type":"journal-article","article-title":"Importance of posttraumatic hypothermia and hyperthermia on the inflammatory response after fluid percussion brain injury: biochemical and immunocytochemical studies","volume":"20","author":"Chatzipanteli","year":"2000","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"jneab85d2bib9","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1038\/sj.jcbfm.9600150","type":"journal-article","article-title":"Influence of therapeutic hypothermia on matrix metalloproteinase activity after traumatic brain injury in rats","volume":"25","author":"Truettner","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"jneab85d2bib10","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.molbrainres.2005.04.006","type":"journal-article","article-title":"The effect of therapeutic hypothermia on the expression of inflammatory response genes following moderate traumatic brain injury in the rat","volume":"138","author":"Truettner","year":"2005","journal-title":"Brain Res. Mol. Brain Res."},{"key":"jneab85d2bib11","doi-asserted-by":"publisher","first-page":"E57-62","DOI":"10.1097\/BRS.0b013e3181b9dc28","type":"journal-article","article-title":"The use of systemic hypothermia for the treatment of an acute cervical spinal cord injury in a professional football player","volume":"35","author":"Cappuccino","year":"2010","journal-title":"Spine"},{"key":"jneab85d2bib12","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1227\/01.NEU.0000367557.77973.5F","type":"journal-article","article-title":"Clinical outcomes using modest intravascular hypothermia after acute cervical spinal cord injury","volume":"66","author":"Levi","year":"2010","journal-title":"Neurosurgery"},{"key":"jneab85d2bib13","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1002\/cne.22014","type":"journal-article","article-title":"Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats","volume":"514","author":"Lo","year":"2009","journal-title":"J. Comp. Neurol."},{"key":"jneab85d2bib14","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1161\/01.STR.31.8.1982","type":"journal-article","article-title":"Effects of delayed intraischemic and postischemic hypothermia on a focal model of transient cerebral ischemia in rats","volume":"31","author":"Kawai","year":"2000","journal-title":"Stroke"},{"key":"jneab85d2bib15","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s13311-011-0035-3","type":"journal-article","article-title":"Hypothermic treatment for acute spinal cord injury","volume":"8","author":"Dietrich","year":"2011","journal-title":"Neurotherapeutics"},{"key":"jneab85d2bib16","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.nurt.2009.10.015","type":"journal-article","article-title":"The evidence for hypothermia as a neuroprotectant in traumatic brain injury","volume":"7","author":"Dietrich","year":"2010","journal-title":"Neurotherapeutics"},{"key":"jneab85d2bib17","doi-asserted-by":"publisher","first-page":"252","DOI":"10.3174\/ajnr.A3175","type":"journal-article","article-title":"Spinal cord hypothermia without systemic hypothermia","volume":"34","author":"Purdy","year":"2013","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"jneab85d2bib18","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1179\/2045772312Y.0000000085","type":"journal-article","article-title":"Effectiveness of local cooling for enhancing tissue ischemia tolerance in people with spinal cord injury","volume":"36","author":"Tzen","year":"2013","journal-title":"J. Spinal. Cord Med."},{"key":"jneab85d2bib19","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/jcbfm.1991.13","type":"journal-article","article-title":"Marked protection by moderate hypothermia after experimental traumatic brain injury","volume":"11","author":"Clifton","year":"1991","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"jneab85d2bib20","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1067\/mem.2002.123697","type":"journal-article","article-title":"Mild hypothermia in neurologic emergency: an update","volume":"40","author":"Inamasu","year":"2002","journal-title":"Ann. Emerg. Med."},{"key":"jneab85d2bib21","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S0022-510X(02)00463-X","type":"journal-article","article-title":"Induced hypothermia in experimental traumatic spinal cord injury: an update","volume":"209","author":"Inamasu","year":"2003","journal-title":"J. Neurol. Sci."},{"key":"jneab85d2bib22","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1016\/S0306-4522(02)00350-0","type":"journal-article","article-title":"Mild hypothermia reduces ICAM-1 expression, neutrophil infiltration and microglia\/monocyte accumulation following experimental stroke","volume":"114","author":"Wang","year":"2002","journal-title":"Neuroscience"},{"key":"jneab85d2bib23","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1097\/00006123-199612000-00024","type":"journal-article","article-title":"Intraischemic hypothermia attenuates neutrophil infiltration in the rat neocortex after focal ischemia-reperfusion injury","volume":"39","author":"Toyoda","year":"1996","journal-title":"Neurosurgery"},{"key":"jneab85d2bib24","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1161\/01.STR.29.10.2171","type":"journal-article","article-title":"Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia: effects on neurologic outcome, infarct size, apoptosis, and inflammation","volume":"29","author":"Maier","year":"1998","journal-title":"Stroke"},{"key":"jneab85d2bib25","first-page":"525","type":"journal-article","article-title":"Postischemic hypothermia attenuates apoptotic cell death in transient focal ischemia in rats","volume":"76","author":"Inamasu","year":"2000","journal-title":"Acta Neurochir. Suppl."},{"key":"jneab85d2bib26","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1038\/jcbfm.2009.81","type":"journal-article","article-title":"The protective effect of early hypothermia on PTEN phosphorylation correlates with free radical inhibition in rat stroke","volume":"29","author":"Lee","year":"2009","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"jneab85d2bib27","type":"journal-article","article-title":"Mild hypothermia attenuates intercellular adhesion molecule-1 induction via activation of extracellular signal-regulated kinase-1\/2 in a focal cerebral ischemia model","volume":"2011","author":"Choi","year":"2011","journal-title":"Stroke Res. Treat"},{"key":"jneab85d2bib28","doi-asserted-by":"publisher","first-page":"C1114","DOI":"10.1152\/ajpcell.00152.2005","type":"journal-article","article-title":"Hypothermia enhances phosphorylation of I{kappa}B kinase and prolongs nuclear localization of NF-{kappa}B in lipopolysaccharide-activated macrophages","volume":"289","author":"Fairchild","year":"2005","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"jneab85d2bib29","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1177\/003693309203700301","type":"journal-article","article-title":"Free radicals and their scavenging in stroke","volume":"37","author":"Belch","year":"1992","journal-title":"Scott. Med. J."},{"key":"jneab85d2bib30","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/S1042-3680(18)30322-X","type":"journal-article","article-title":"Brain attack Acute therapeutic interventions. Free radical scavengers and antioxidants","volume":"8","author":"Hall","year":"1997","journal-title":"Neurosurg. Clin. N. Am."},{"key":"jneab85d2bib31","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1001\/archinte.168.14.1522","type":"journal-article","article-title":"Prevalence of hearing loss and differences by demographic characteristics among US adults: data from the national health and nutrition examination survey, 1999\u20132004","volume":"168","author":"Agrawal","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"jneab85d2bib32","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1080\/000164800750000793","type":"journal-article","article-title":"Expression of heat shock protein 72 in rat cochlea with cisplatin-induced acute ototoxicity","volume":"120","author":"Oh","year":"2000","journal-title":"Acta. Otolaryngol."},{"key":"jneab85d2bib33","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0022-5223(05)80006-6","type":"journal-article","article-title":"Profound systemic hypothermia inhibits the release of neurotransmitter amino acids in spinal cord ischemia","volume":"110","author":"Rokkas","year":"1995","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"jneab85d2bib34","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1161\/01.STR.27.5.913","type":"journal-article","article-title":"Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization","volume":"27","author":"Nakashima","year":"1996","journal-title":"Stroke"},{"key":"jneab85d2bib35","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1161\/01.STR.0000091269.67384.E7","type":"journal-article","article-title":"Mild hypothermia inhibits inflammation after experimental stroke and brain inflammation","volume":"34","author":"Deng","year":"2003","journal-title":"Stroke"},{"key":"jneab85d2bib36","doi-asserted-by":"publisher","first-page":"3921","DOI":"10.1523\/JNEUROSCI.22-10-03921.2002","type":"journal-article","article-title":"Influence of mild hypothermia on inducible nitric oxide synthase expression and reactive nitrogen production in experimental stroke and inflammation","volume":"22","author":"Han","year":"2002","journal-title":"J. Neurosci."},{"key":"jneab85d2bib37","doi-asserted-by":"publisher","first-page":"289","DOI":"10.3171\/jns.2005.103.2.0289","type":"journal-article","article-title":"Reduction in levels of matrix metalloproteinases and increased expression of tissue inhibitor of metalloproteinase-2 in response to mild hypothermia therapy in experimental stroke","volume":"103","author":"Lee","year":"2005","journal-title":"J. Neurosurg."},{"key":"jneab85d2bib38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0170682","type":"journal-article","article-title":"Anesthesia-induced hypothermia attenuates early-phase blood-brain barrier disruption but not infarct volume following cerebral ischemia","volume":"12","author":"Liu","year":"2017","journal-title":"PLoS One"},{"key":"jneab85d2bib39","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.brainres.2007.10.052","type":"journal-article","article-title":"Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat: effects on BBB breakdown and MMP expression in the acute and subacute phase","volume":"1188","author":"Nagel","year":"2008","journal-title":"Brain Res."},{"key":"jneab85d2bib40","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/S0006-8993(03)03088-9","type":"journal-article","article-title":"Topographically graded postischemic presence of metalloproteinases is inhibited by hypothermia","volume":"984","author":"Wagner","year":"2003","journal-title":"Brain Res."},{"key":"jneab85d2bib41","doi-asserted-by":"publisher","first-page":"H558","DOI":"10.1152\/ajpheart.01275.2004","type":"journal-article","article-title":"Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia","volume":"289","author":"Gidday","year":"2005","journal-title":"Am. J. Physiol. Heart Circulatory Physiol."},{"key":"jneab85d2bib42","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1097\/01.WCB.0000090680.07515.C8","type":"journal-article","article-title":"Neutrophil infiltration increases matrix metalloproteinase-9 in the ischemic brain after occlusion\/reperfusion of the middle cerebral artery in rats","volume":"23","author":"Justicia","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"jneab85d2bib43","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1097\/mao.0000000000002373","type":"journal-article","article-title":"Anatomical correlates and surgical considerations for localized therapeutic hypothermia application in cochlear implantation surgery","volume":"40","author":"Perez","year":"2019","journal-title":"Otol. Neurotol."},{"key":"jneab85d2bib44","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.heares.2016.05.015","type":"journal-article","article-title":"A cool approach to reducing electrode-induced trauma: localized therapeutic hypothermia conserves residual hearing in cochlear implantation","volume":"339","author":"Tamames","year":"2016","journal-title":"Hear. Res."},{"key":"jneab85d2bib45","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1097\/AUD.0000000000000529","type":"journal-article","article-title":"Theoretical evaluation and experimental validation of localized therapeutic hypothermia application to preserve residual hearing after cochlear implantation","volume":"39","author":"Tamames","year":"2018","journal-title":"Ear Hear"},{"key":"jneab85d2bib46","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1016\/0003-4975(94)91350-1","type":"journal-article","article-title":"Computer simulation of brain cooling during cardiopulmonary bypass","volume":"57","author":"Dexter","year":"1994","journal-title":"Ann. Thorac Surg."},{"key":"jneab85d2bib47","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1114\/1.1554924","type":"journal-article","article-title":"Cooling and rewarming for brain ischemia or injury: theoretical analysis","volume":"31","author":"Diao","year":"2003","journal-title":"Ann. Biomed. Eng."},{"key":"jneab85d2bib48","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1109\/TNSRE.2007.908429","type":"journal-article","article-title":"Thermal impact of an active 3-D microelectrode array implanted in the brain","volume":"15","author":"Kim","year":"2007","journal-title":"IEEE Trans. Neural Syst. Rehabil. Eng."},{"key":"jneab85d2bib49","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1097\/AUD.0000000000000529","type":"journal-article","article-title":"Theoretical evaluation and experimental validation of localized therapeutic hypothermia application to preserve residual hearing after cochlear implantation","volume":"39","author":"Tamames","year":"2017","journal-title":"Ear Hear"},{"key":"jneab85d2bib50","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s00421-007-0451-6","type":"journal-article","article-title":"Targeted brain hypothermia induced by an interstitial cooling device in human neck: theoretical analyses","volume":"101","author":"Wang","year":"2007","journal-title":"Eur. J. Appl. Physiol."},{"key":"jneab85d2bib51","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1007\/s11517-019-01962-7","type":"journal-article","article-title":"Inducing therapeutic hypothermia via selective brain cooling: a finite element modeling analysis","volume":"57","author":"Yin","year":"2019","journal-title":"Med. Biol. Eng. Comput."},{"key":"jneab85d2bib52","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2560\/9\/5\/056015","type":"journal-article","article-title":"Comprehensive characterization and failure modes of tungsten microwire arrays in chronic neural implants","volume":"9","author":"Prasad","year":"2012","journal-title":"J. Neural. Eng."},{"key":"jneab85d2bib53","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.biomaterials.2018.09.040","type":"journal-article","article-title":"Neuroinflammation, oxidative stress, and blood-brain barrier (BBB) disruption in acute Utah electrode array implants and the effect of deferoxamine as an iron chelator on acute foreign body response","volume":"188","author":"Bennett","year":"2018","journal-title":"Biomaterials"},{"key":"jneab85d2bib54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biomaterials.2018.02.036","type":"journal-article","article-title":"Blood brain barrier (BBB)-disruption in intracortical silicon microelectrode implants","volume":"164","author":"Bennett","year":"2018","journal-title":"Biomaterials"},{"key":"jneab85d2bib55","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","type":"journal-article","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"jneab85d2bib56","first-page":"6","type":"journal-article","article-title":"Determining significant fold differences in gene expression analysis","author":"Butte","year":"2001","journal-title":"Pac. Symp. Biocomput."},{"key":"jneab85d2bib57","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.yjmcc.2007.11.020","type":"journal-article","article-title":"Functional and metabolic remodelling in GLUT4-deficient hearts confers hyper-responsiveness to substrate intervention","volume":"44","author":"Huggins","year":"2008","journal-title":"J. Mol. Cell. Cardiol."},{"key":"jneab85d2bib58","doi-asserted-by":"publisher","first-page":"3697","DOI":"10.1073\/pnas.0500369102","type":"journal-article","article-title":"Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors","volume":"102","author":"Peart","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"jneab85d2bib59","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.stem.2008.05.018","type":"journal-article","article-title":"Transcriptome analysis of the normal human mammary cell commitment and differentiation process","volume":"3","author":"Raouf","year":"2008","journal-title":"Cell Stem Cell"},{"key":"jneab85d2bib60","author":"Maekawa","year":"2012","type":"web-resource"},{"key":"jneab85d2bib61","author":"Jiang","year":"2017","type":"report"},{"key":"jneab85d2bib62","author":"Cooper","year":"2017","type":"report"},{"key":"jneab85d2bib63","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.jneumeth.2008.12.030","type":"journal-article","article-title":"Theoretical evaluations of therapeutic systemic and local cerebral hypothermia","volume":"178","author":"Keller","year":"2009","journal-title":"J. Neurosci. Methods"},{"key":"jneab85d2bib64","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1177\/0954411911400156","type":"journal-article","article-title":"Experimental study and model validation of selective spinal cord and brain hypothermia induced by a simple torso-cooling pad","volume":"225","author":"Smith","year":"2011","journal-title":"Proc. Inst. Mech. Eng. H"},{"key":"jneab85d2bib65","doi-asserted-by":"publisher","first-page":"S186","DOI":"10.1097\/CCM.0b013e3181aa5241","type":"journal-article","article-title":"Mechanisms of action, physiological effects, and complications of hypothermia","volume":"37","author":"Polderman","year":"2009","journal-title":"Crit. Care Med."},{"key":"jneab85d2bib66","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.jtherbio.2004.04.001","type":"journal-article","article-title":"A model of deep experimental hypothermia and rewarming in rat","volume":"29","author":"Alva","year":"2004","journal-title":"J. Therm. Biol."},{"key":"jneab85d2bib67","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/957054","type":"journal-article","article-title":"Oxidative stress and antioxidant activity in hypothermia and rewarming: can RONS modulate the beneficial effects of therapeutic hypothermia?","volume":"2013","author":"Alva","year":"2013","journal-title":"Oxid. Med. Cell Longevity"},{"key":"jneab85d2bib68","doi-asserted-by":"publisher","first-page":"186","DOI":"10.4103\/bc.bc_28_17","type":"journal-article","article-title":"Therapeutic hypothermia and targeted temperature management for traumatic brain injury: experimental and clinical experience","volume":"3","author":"Dietrich","year":"2017","journal-title":"Brain Circ."},{"key":"jneab85d2bib69","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1007\/s00134-003-2152-x","type":"journal-article","article-title":"Application of therapeutic hypothermia in the ICU: opportunities and pitfalls of a promising treatment modality. Part 1: indications and evidence","volume":"30","author":"Polderman","year":"2004","journal-title":"Intensive Care Med."},{"key":"jneab85d2bib70","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1186\/cc5023","type":"journal-article","article-title":"Equipment review: cooling catheters to induce therapeutic hypothermia?","volume":"10","author":"Polderman","year":"2006","journal-title":"Crit Care"},{"key":"jneab85d2bib71","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1097\/CCM.0b013e3181962ad5","type":"journal-article","article-title":"Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods","volume":"37","author":"Polderman","year":"2009","journal-title":"Crit. Care Med."},{"key":"jneab85d2bib72","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1471-4159.2004.02711.x","type":"journal-article","article-title":"Intraischaemic hypothermia reduces free radical production and protects against ischaemic insults in cultured hippocampal slices","volume":"91","author":"McManus","year":"2004","journal-title":"J. Neurochem."},{"key":"jneab85d2bib73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj3260001","type":"journal-article","article-title":"Caspases: the executioners of apoptosis","volume":"326","author":"Cohen","year":"1997","journal-title":"Biochem. J."},{"key":"jneab85d2bib74","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/sj.cdd.4400344","type":"journal-article","article-title":"Caspases are the main executioners of Fas-mediated apoptosis, irrespective of the ceramide signalling pathway","volume":"5","author":"Gamen","year":"1998","journal-title":"Cell Death Differ."},{"key":"jneab85d2bib75","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.jss.2004.08.002","type":"journal-article","article-title":"Expressions of intestinal NF-kappaB, TNF-alpha, and IL-6 following traumatic brain injury in rats","volume":"123","author":"Hang","year":"2005","journal-title":"J. Surg. Res."},{"key":"jneab85d2bib76","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3389\/fnmol.2015.00077","type":"journal-article","article-title":"NF-kappaB signaling pathways in neurological inflammation: a mini review","volume":"8","author":"Shih","year":"2015","journal-title":"Front Mol. Neurosci."},{"key":"jneab85d2bib77","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1177\/10454411930040020401","type":"journal-article","article-title":"Matrix metalloproteinases: a review","volume":"4","author":"Birkedal-Hansen","year":"1993","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"jneab85d2bib78","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.ijporl.2012.01.013","type":"journal-article","article-title":"Matrix metalloproteinase inhibitor attenuates cochlear lateral wall damage induced by intratympanic instillation of endotoxin","volume":"76","author":"Choi","year":"2012","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"jneab85d2bib79","doi-asserted-by":"publisher","first-page":"8","DOI":"10.22088\/IJMCM.BUMS.7.1.8","type":"journal-article","article-title":"Downregulation of matrix metalloproteinases 2 and 9 is involved in the protective effect of trehalose on spinal cord injury","volume":"7","author":"Mirzaie","year":"2018","journal-title":"Int. J. Mol. Cell Med."},{"key":"jneab85d2bib80","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1177\/1073858402238517","type":"journal-article","article-title":"Matrix metalloproteinases and neuroinflammation in multiple sclerosis","volume":"8","author":"Rosenberg","year":"2002","journal-title":"Neuroscientist"},{"key":"jneab85d2bib81","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1097\/MAO.0000000000000787","type":"journal-article","article-title":"Changes in gene expression and hearing thresholds after cochlear implantation. Otology & neurotology: official publication of the American otological Society","volume":"36","author":"Zhang","year":"2015","journal-title":"Am. Neurotol Soc. Eur. Academy Otol. Neurotol."},{"key":"jneab85d2bib82","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1179\/016164110X12670144526228","type":"journal-article","article-title":"Mild hypothermia reduces ischemic neuron death via altering the expression of p53 and bcl-2","volume":"32","author":"Zhang","year":"2010","journal-title":"Neurol. Res."},{"key":"jneab85d2bib83","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0169-328X(01)00247-9","type":"journal-article","article-title":"Mild hypothermia increases Bcl-2 protein expression following global cerebral ischemia","volume":"95","author":"Zhang","year":"2001","journal-title":"Brain Res. Mol. Brain Res."},{"key":"jneab85d2bib84","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1146\/annurev.neuro.20.1.245","type":"journal-article","article-title":"Bcl-2 gene family in the nervous system","volume":"20","author":"Merry","year":"1997","journal-title":"Annu. Rev. Neurosci."},{"key":"jneab85d2bib85","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1023\/A:1020709814456","type":"journal-article","article-title":"Targeted disruption of the bcl-2 gene in mice exacerbates focal ischemic brain injury","volume":"14","author":"Hata","year":"1999","journal-title":"Metab. Brain Dis."},{"key":"jneab85d2bib86","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1523\/JNEUROSCI.16-02-00486.1996","type":"journal-article","article-title":"Overexpression of Bcl-2 with herpes simplex virus vectors protects CNS neurons against neurological insults in vitro and in vivo","volume":"16","author":"Lawrence","year":"1996","journal-title":"J. Neurosci."},{"key":"jneab85d2bib87","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1016\/0896-6273(94)90266-6","type":"journal-article","article-title":"Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia","volume":"13","author":"Martinou","year":"1994","journal-title":"Neuron"}],"container-title":["Journal of Neural Engineering"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2","content-type":"text\/html","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T15:34:22Z","timestamp":1768664062000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1741-2552\/ab85d2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,1]]},"references-count":87,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,4,28]]},"published-print":{"date-parts":[[2020,4,1]]}},"URL":"https:\/\/doi.org\/10.1088\/1741-2552\/ab85d2","relation":{},"ISSN":["1741-2560","1741-2552"],"issn-type":[{"value":"1741-2560","type":"print"},{"value":"1741-2552","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,1]]},"assertion":[{"value":"Therapeutic hypothermia reduces cortical inflammation associated with utah array implants","name":"article_title","label":"Article Title"},{"value":"Journal of Neural Engineering","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2020 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2019-12-02","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2020-04-02","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2020-04-28","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}