{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:05:51Z","timestamp":1789049151766,"version":"build-2803163510"},"reference-count":102,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T00:00:00Z","timestamp":1648252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002772","name":"University of Cagliari","doi-asserted-by":"publisher","award":["FIR 2018; 2019, 2020"],"award-info":[{"award-number":["FIR 2018; 2019, 2020"]}],"id":[{"id":"10.13039\/501100002772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002772","name":"University of Cagliari","doi-asserted-by":"publisher","award":["FIR 2018, 2019, 2020"],"award-info":[{"award-number":["FIR 2018, 2019, 2020"]}],"id":[{"id":"10.13039\/501100002772","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We have previously shown that bilateral common carotid artery occlusion followed by reperfusion (BCCAO\/R) is a model to study early hypoperfusion\/reperfusion-induced changes in biomarkers of the tissue physiological response to oxidative stress and inflammation. Thus in this study, we investigate with immunochemical assays if a single dose of beta-caryophyllene (BCP), administered before the BCCAO\/R, can modulate the TRPV1, BDNF, and trkB receptor in the brain cortex; the glial markers GFAP and Iba1 were also examined. Frontal and temporal-occipital cortical regions were analyzed in two groups of male rats, sham-operated and submitted to BCCAO\/R. Six hours before surgery, one group was gavage fed a dose of BCP (40 mg\/per rat in 300 \u03bcL of sunflower oil), the other was pre-treated with the vehicle alone. Western blot analysis showed that, in the frontal cortex of vehicle-treated rats, the BCCAO\/R caused a TRPV1 decrease, an increment of trkB and GFAP, no change in BDNF and Iba1. The BCP treatment caused a decrease of BDNF and an increase of trkB levels in both sham and BCCAO\/R conditions while inducing opposite changes in the case of TRPV1, whose levels became higher in BCCAO\/R and lower in sham conditions. Present results highlight the role of BCP in modulating early events of the cerebral inflammation triggered by the BCCAO\/R through the regulation of TRPV1 and the BDNF-trkB system.<\/jats:p>","DOI":"10.3390\/ijms23073633","type":"journal-article","created":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:27:51Z","timestamp":1648416471000},"page":"3633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Anti-Inflammatory Effect of Beta-Caryophyllene Mediated by the Involvement of TRPV1, BDNF and trkB in the Rat Cerebral Cortex after Hypoperfusion\/Reperfusion"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3343-7861","authenticated-orcid":false,"given":"Maria Pina","family":"Serra","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4203-313X","authenticated-orcid":false,"given":"Marianna","family":"Boi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Carta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-5780","authenticated-orcid":false,"given":"Elisabetta","family":"Murru","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3527-4197","authenticated-orcid":false,"given":"Gianfranca","family":"Carta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiano","family":"Banni","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-3597","authenticated-orcid":false,"given":"Marina","family":"Quartu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.2174\/0929867321666131228205146","article-title":"Innate inflammatory responses in stroke: Mechanisms and potential therapeutic targets","volume":"21","author":"Kim","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s12974-019-1516-2","article-title":"Rosenberg GA. Neuroinflammation: Friend and foe for ischemic stroke","volume":"16","author":"Jayaraj","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.5853\/jos.2014.16.3.131","article-title":"Magnetic resonance imaging in acute ischemic stroke treatment","volume":"16","author":"Kim","year":"2014","journal-title":"J. Stroke"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.12688\/f1000research.11913.1","article-title":"Rehabilitation following hemorrhagic stroke: Building the case for stroke-subtype specific recovery therapies","volume":"6","author":"Kitago","year":"2017","journal-title":"F1000Res"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"101715","DOI":"10.1016\/j.tice.2021.101715","article-title":"Systematic comparison of basic animal models of cerebral hypoperfusion","volume":"75","author":"Chrishtop","year":"2021","journal-title":"Tissue Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1016\/j.jacc.2019.12.072","article-title":"Primary and Secondary Prevention of Ischemic Stroke and Cerebral Hemorrhagie","volume":"75","author":"Diener","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1152\/jappl.1991.71.4.1185","article-title":"Oxygen radical mechanisms of brain injury following ischemia and reperfusion","volume":"71","author":"Traystman","year":"1991","journal-title":"J. Appl. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.arr.2016.09.006","article-title":"Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: An aging effect","volume":"34","author":"Cai","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.neuropharm.2008.01.005","article-title":"Mechanisms of ischemic brain damage","volume":"55","author":"Doyle","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_10","first-page":"548","article-title":"The interplay of MicroRNAs in the inflammatory mechanisms following ischemic stroke. J. Neuropathol","volume":"76","author":"Khoshnam","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_11","first-page":"507","article-title":"Effects of low dose methotrexate in cerebral ischemia reperfusion injury in rat","volume":"32","author":"Bakar","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s11011-018-0187-5","article-title":"Vanillic acid attenuates cerebral hyperemia, blood-brain barrier disruption and anxiety-like behaviors in rats following transient bilateral common carotid occlusion and reperfusion","volume":"33","author":"Khoshnam","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00229648","article-title":"Local cerebral glucose utilisation following acute and chronic bilateral carotid artery ligation in Wistar rats: Relation to changes in local cerebral blood flow","volume":"95","author":"Tsuchiya","year":"1993","journal-title":"Exp. Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.phrs.2003.08.005","article-title":"Nimopidine attenuates biochemical, behavioral and histopathological alterations induced by acute transient and long-term bilateral common carotid occlusion in rats","volume":"49","author":"Yanpallewar","year":"2004","journal-title":"Pharmacol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1476-511X-11-8","article-title":"Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion","volume":"11","author":"Quartu","year":"2012","journal-title":"Lipids Health Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12944-016-0389-y","article-title":"Involvement of the endocannabinoid system in the physiological response to transient common carotid artery occlusion and reperfusion","volume":"16","author":"Quartu","year":"2017","journal-title":"Lipids Health Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ganesana, M., and Venton, B.J. (2017). Early changes in transient adenosine during cerebral ischemia and reperfusion injury. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196932"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12944-018-0661-4","article-title":"Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion","volume":"17","author":"Poddighe","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Carta, G., Poddighe, L., Serra, M.P., Boi, M., Melis, T., Lisai, S., Murru, E., Muredda, L., Collu, M., and Banni, S. (2018). Preventive effects of resveratrol on endocannabinoid system and synaptic protein modifications in rat cerebral cortex challenged by bilateral common carotid artery occlusion and reperfusion. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020426"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Serra, M.P., Boi, M., Poddighe, L., Melis, T., Lai, Y., Carta, G., and Quartu, M. (2019). Resveratrol Regulates BDNF, trkB, PSA-NCAM, and Arc Expression in the Rat Cerebral Cortex after Bilateral Common Carotid Artery Occlusion and Reperfusion. Nutrients, 11.","DOI":"10.3390\/nu11051000"},{"key":"ref_21","first-page":"314","article-title":"Protective Effects of Adrenomedullin on Rat Cerebral Tissue After Transient Bilateral Common Carotid Artery Occlusion and Reperfusion","volume":"35","author":"Gunes","year":"2020","journal-title":"Braz. J. Cardiovasc. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/0031-9422(75)83045-7","article-title":"Mono- and sesquiterpene hydrocarbons of the essential oil of Cannabis sativa","volume":"14","author":"Hendriks","year":"1975","journal-title":"Phytochemistry"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Francomano, F., Caruso, A., Barbarossa, A., Fazio, A., La Torre, C., Ceramella, J., Mallamaci, R., Saturnino, C., Iacopetta, D., and Sinicropi, M.S. (2019). \u03b2-Caryophyllene: A Sesquiterpene with Countless Biological Properties. Appl. Sci., 9.","DOI":"10.3390\/app9245420"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9099","DOI":"10.1073\/pnas.0803601105","article-title":"Beta-caryophyllene is a dietary cannabinoid","volume":"105","author":"Gertsch","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1021\/cb500177c","article-title":"Functionalization of \u03b2-caryophyllene generates novel polypharmacology in the endocannabinoid system","volume":"9","author":"Chicca","year":"2014","journal-title":"ACS Chem. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1016\/j.bmcl.2014.04.112","article-title":"trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator-activated receptor-\u03b1","volume":"24","author":"Wu","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Scandiffio, R., Geddo, F., Cottone, E., Querio, G., Antoniotti, S., Gallo, M.P., Maffei, M.E., and Bovolin, P. (2020). Protective Effects of (E)-\u03b2-Caryophyllene (BCP) in Chronic Inflammation. Nutrients, 12.","DOI":"10.3390\/nu12113273"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1111\/j.1476-5381.2011.01238.x","article-title":"Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects","volume":"163","author":"Russo","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.euroneuro.2013.10.008","article-title":"The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain","volume":"24","author":"Klauke","year":"2014","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1096\/fj.02-0901fje","article-title":"A central role for the nuclear factor-kappaB pathway in anti-inflammatory and proinflammatory actions of mechanical strain","volume":"17","author":"Agarwal","year":"2003","journal-title":"FASEB J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejphar.2007.04.059","article-title":"Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea","volume":"569","author":"Fernandes","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.ajpath.2010.11.052","article-title":"\u03b2-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPAR\u03b3 pathway","volume":"178","author":"Bento","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.freeradbiomed.2012.01.014","article-title":"\u03b2-Caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid receptor-dependent manner","volume":"52","author":"Mukhopadhyay","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1089\/jmf.2012.2283","article-title":"Protective effect of \u03b2-caryophyllene, a natural bicyclic sesquiterpene, against cerebral ischemic injury","volume":"16","author":"Chang","year":"2013","journal-title":"J. Med. Food"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/39807","article-title":"The capsaicin receptor: A heat-activated ION channel in the pain pathway","volume":"389","author":"Caterina","year":"1997","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev.neuro.24.1.487","article-title":"The vanilloid receptor: A molecular gateway to the pain pathway","volume":"24","author":"Caterina","year":"2011","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nrd2280","article-title":"The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept","volume":"6","author":"Szallasi","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev-cellbio-101011-155833","article-title":"TRP channels and pain","volume":"29","author":"Julius","year":"2013","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1111\/joa.12529","article-title":"TRPV1 receptor in the human trigeminal ganglion and spinal nucleus: Immunohistochemical localization and comparison with the neuropeptides CGRP and SP","volume":"229","author":"Quartu","year":"2016","journal-title":"J. Anat."},{"key":"ref_40","first-page":"159","article-title":"Vanilloid (capsaicin) receptors and mechanisms","volume":"51","author":"Szallasi","year":"1999","journal-title":"Pharmacol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6155","DOI":"10.1073\/pnas.97.11.6155","article-title":"Direct activation of capsaicin receptors by products of lipoxygenases: Endogenous capsaicin-like substances","volume":"97","author":"Hwang","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.pain.2005.06.024","article-title":"Investigation of the role of TRPV1 receptors in acute and chronic nociceptive processes using gene-deficient mice","volume":"117","author":"Helyes","year":"2005","journal-title":"Pain"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/bjp.2008.351","article-title":"The pharmacological challenge to tame the transient receptor potential vanilloid-1 (TRPV1) nocisensor","volume":"155","author":"Holzer","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"837","DOI":"10.3390\/ph5080837","article-title":"Role of transient receptor potential vanilloid 1 in inflammation and autoimmune diseases","volume":"5","author":"Tsuji","year":"2012","journal-title":"Pharmaceuticals"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1136\/jnnp-2014-308813","article-title":"TRPV1, CGRP and SP in scalp arteries of patients suffering from chronic migraine","volume":"86","author":"Quartu","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.bbi.2017.03.007","article-title":"Modulation of neuroinflammation: Role and therapeutic potential of TRPV1 in the neuro-immune axis","volume":"64","author":"Kong","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5138","DOI":"10.1016\/j.cell.2021.08.012","article-title":"Structural snapshots of TRPV1 reveal mechanism of polymodal functionality","volume":"184","author":"Zhang","year":"2021","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"612480","DOI":"10.3389\/fncel.2020.612480","article-title":"Beyond Neuronal Heat Sensing: Diversity of TRPV1 Heat-Capsaicin Receptor-Channel Functions","volume":"14","author":"Shuba","year":"2021","journal-title":"Front. Cell Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.molbrainres.2004.12.003","article-title":"Expression and distribution of vanilloid receptor 1 (TRPV1) in the adult rat brain","volume":"135","author":"Kedei","year":"2005","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"15292","DOI":"10.1038\/ncomms15292","article-title":"TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice","volume":"8","author":"Marrone","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s12974-019-1487-3","article-title":"TRPV1 mediates astrocyte activation and interleukin-1\u03b2 release induced by hypoxic ischemia (HI)","volume":"16","author":"Yang","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"R149","DOI":"10.1152\/ajpregu.00329.2013","article-title":"Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90 min after reperfusion","volume":"306","author":"Cao","year":"2014","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3389\/fnmol.2018.00487","article-title":"Cannabinoid Ligands Targeting TRP Channels","volume":"11","author":"Muller","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.npep.2016.01.003","article-title":"TRPV currents and their role in the nociception and neuroplasticity","volume":"57","author":"Satheesh","year":"2016","journal-title":"Neuropeptides"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Rosenbaum, T., Awaya, M., and Gordon, S.E. (2002). Subunit modification and association in VR1 ion channels. BMC Neurosci., 3.","DOI":"10.1186\/1471-2202-3-4"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1210\/endo-129-3-1289","article-title":"Primary structure and biological activity of human brain-derived neurotrophic factor","volume":"129","author":"Rosenthal","year":"1991","journal-title":"Endocrinology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e00861","DOI":"10.1002\/brb3.861","article-title":"Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low-avoidance) and resistance (Roman high-avoidance) to stress-induced depression","volume":"7","author":"Serra","year":"2017","journal-title":"Brain Behav."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1002\/j.1460-2075.1989.tb08545.x","article-title":"trkB, a novel tyrosine protein kinase receptor expressed during mouse neural development","volume":"8","author":"Klein","year":"1989","journal-title":"EMBO J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1023\/A:1007677003387","article-title":"Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000)","volume":"25","author":"Eng","year":"2000","journal-title":"Neurochem. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/glia.10149","article-title":"Intracellular signaling in M-CSF-induced microglia activation: Role of Iba1","volume":"40","author":"Imai","year":"2002","journal-title":"GLIA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"36764","DOI":"10.1021\/acsami.8b14790","article-title":"Urokinase-conjugated magnetite nanoparticles as a promising drug delivery system for targeted thrombolysis: Synthesis and preclinical evaluation","volume":"10","author":"Prilepskii","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/sj.bjp.0705467","article-title":"Anandamide and vanilloid TRPV1 receptors","volume":"140","author":"Ross","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1016\/j.lfs.2005.05.021","article-title":"Lipids as regulators of the activity of transient receptor potential type V1 (TRPV1) channels","volume":"77","year":"2005","journal-title":"Life Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1523\/JNEUROSCI.21-04-01104.2001","article-title":"Anandamide excites central terminals of dorsal root ganglion neurons via vanilloid receptor-1 activation","volume":"21","author":"Tognetto","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/sj.bjp.0704900","article-title":"Therapeutic effect of the endogenous fatty acid amide, palmitoylethanolamide, in rat acute inflammation: Inhibition of nitric oxide and cyclo-oxygenase systems","volume":"137","author":"Costa","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/s12035-013-8487-6","article-title":"Glia and mast cells as targets for palmitoylethanolamide, an anti-inflammatory and neuroprotective lipid mediator","volume":"48","author":"Skaper","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1111\/bph.13084","article-title":"The anti-inflammatory mediator palmitoylethanolamide enhances the levels of 2-arachidonoyl-glycerol and potentiates its actions at TRPV1 cation channels","volume":"173","author":"Petrosino","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1124\/mol.104.006353","article-title":"The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide","volume":"67","author":"Fu","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(98)00649-9","article-title":"Endoccabinoids","volume":"359","author":"Mechoulam","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1111\/bph.12029","article-title":"Activation and desensitization of TRPV1 channels in sensory neurons by the PPAR\u03b1 agonist palmitoylethanolamide","volume":"168","author":"Ambrosino","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1016\/S0024-3205(96)00537-1","article-title":"Specific binding of [3H]resiniferatoxin by human and rat preoptic area, locus ceruleus, medial hypothalamus, reticular formation and ventral thalamus membrane preparations","volume":"59","author":"Acs","year":"1996","journal-title":"Life Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.1073\/pnas.97.7.3655","article-title":"Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1- like immunoreactivity, in the central nervous system of the rat and human","volume":"97","author":"Mezey","year":"2000","journal-title":"Proc. Natl. Acad. Sci USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.brainres.2003.10.001","article-title":"[3H]Resiniferatoxin autoradiography in the CNS of wild-type and TRPV1 null mice defines TRPV1 (VR-1) protein distribution","volume":"995","author":"Roberts","year":"2004","journal-title":"Brain Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.neuroscience.2006.02.074","article-title":"Immunohistochemical localization of cannabinoid type 1 and vanilloid transient receptor potential vanilloid type 1 receptors in the mouse brain","volume":"139","author":"Cristino","year":"2006","journal-title":"Neuroscience"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/1744-8069-2-34","article-title":"Hot receptors in the brain","volume":"2","author":"Steenland","year":"2006","journal-title":"Mol. Pain"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5067","DOI":"10.1523\/JNEUROSCI.6451-10.2011","article-title":"Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells","volume":"31","author":"Cavanaugh","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"755955","DOI":"10.3389\/fncel.2021.755955","article-title":"Activation and Role of Astrocytes in Ischemic Stroke","volume":"15","author":"Shen","year":"2021","journal-title":"Front. Cell Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1369\/0022155413513589","article-title":"Vanilloid receptor-1 (TRPV1) expression and function in the vasculature of the rat","volume":"62","author":"Toth","year":"2014","journal-title":"J. Histochem. Cytochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.neulet.2003.12.051","article-title":"The vanilloid receptor-1 is expressed in rat spinal dorsal horn astrocytes","volume":"357","author":"Doly","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"573256","DOI":"10.3389\/fimmu.2020.573256","article-title":"Protective Functions of Reactive Astrocytes Following Central Nervous System Insult","volume":"11","author":"Linnerbauer","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/S0006-8993(01)02640-3","article-title":"Activated astrocytes with glycogen accumulation in ischemic penumbra during the early stage of brain infarction: Immunohistochemical and electron microscopic studies","volume":"909","author":"Kajihara","year":"2001","journal-title":"Brain Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"106355","DOI":"10.1016\/j.intimp.2020.106355","article-title":"Muscone relieves inflammatory pain by inhibiting microglial activation- mediated inflammatory response via abrogation of the NOX4\/JAK2-STAT3 pathway and NLRP3 inflammasome","volume":"82","author":"Yu","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/jcbfm.1991.162","article-title":"The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia","volume":"11","author":"Morioka","year":"1991","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_84","first-page":"65","article-title":"Early microglial reaction following mild forebrain ischemia induced by common carotid artery occlusion in rats","volume":"862","year":"2000","journal-title":"Brain Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0169-328X(96)00002-2","article-title":"Regional brain-derived neurotrophic factor mRNA and protein levels following transient forebrain ischemia in the rat","volume":"38","author":"Kokaia","year":"1996","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1073\/pnas.89.2.648","article-title":"Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma","volume":"89","author":"Lindvall","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0896-6273(93)90307-D","article-title":"Increased production of the TrkB protein tyrosine kinase receptor after brain insults","volume":"10","author":"Merlio","year":"1993","journal-title":"Neuron"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S0006-8993(98)00385-0","article-title":"Enhanced expression of full-length TrkB receptors in young rat brain with hypoxic\/ischemic injury","volume":"797","author":"Narumiya","year":"1998","journal-title":"Brain Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1111\/j.1476-5381.2011.01455.x","article-title":"Cannabinoid CB1 receptors transactivate multiple receptor tyrosine kinases and regulate serine\/threonine kinases to activate ERK in neuronal cells","volume":"165","author":"Dalton","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"19115","DOI":"10.1073\/pnas.0509494102","article-title":"Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor","volume":"102","author":"Berghuis","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e6493","DOI":"10.7717\/peerj.6493","article-title":"Dual mechanism of TRKB activation by anandamide through CB1 and TRPV1 receptors","volume":"7","author":"Diniz","year":"2019","journal-title":"PeerJ"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.ajpath.2012.11.024","article-title":"Activation of cannabinoid CB2 receptor-mediated AMPK\/CREB pathway reduces cerebral ischemic injury","volume":"182","author":"Choi","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"8070","DOI":"10.1523\/JNEUROSCI.2838-19.2020","article-title":"BDNF Activates Postsynaptic TrkB Receptors to Induce Endocannabinoid Release and Inhibit Presynaptic Calcium Influx at a Calyx-Type Synapse","volume":"40","author":"Wu","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1152\/jn.00554.2013","article-title":"BDNF-endocannabinoid interactions at neocortical inhibitory synapses require phospholipase C signaling","volume":"111","author":"Zhao","year":"2014","journal-title":"J. Neurophysiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1093\/cercor\/bhz081","article-title":"BDNF Controls Bidirectional Endocannabinoid Plasticity at Corticostriatal Synapses","volume":"30","author":"Gangarossa","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3237","DOI":"10.2174\/1381612822666160311115226","article-title":"Polypharmacological properties and therapeutic potential of \u03b2-Caryophyllene: A dietary phytocannabinoid of pharmaceutical promise","volume":"22","author":"Sharma","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.2174\/1381612824666180912151412","article-title":"\u03b2-caryophyllene delivery systems: Enhancing the oral pharmacokinetic and stability","volume":"24","author":"Santos","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1177\/1091581816655303","article-title":"toxicological evaluation of \u03b2-caryophyllene oil: Subchronic toxicity in rats","volume":"35","author":"Schmitt","year":"2016","journal-title":"Int. J. Toxicol."},{"key":"ref_99","unstructured":"US Code of Federal Regulations (2022). CFR Title 21: Section 172.515, Synthetic Flavoring Substances and Adjuvants."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0022-510X(89)90098-1","article-title":"Forebrain ischemia induced by temporary bilateral common carotid occlusion in normotensive rats","volume":"90","author":"Iwasaki","year":"1989","journal-title":"J. Neurol. Sci."},{"key":"ref_101","unstructured":"Paxinos, G., and Watson, C. (2007). The Rat Brain in Stereotaxic Coordinates, Elsevier. [6th ed.]."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurements with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3633\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:44:01Z","timestamp":1760136241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3633"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,26]]},"references-count":102,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23073633"],"URL":"https:\/\/doi.org\/10.3390\/ijms23073633","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,26]]}}}