Neuropathic pain releasing calcitonin gene related peptide protects against stroke in rats.

Neuropathic pain (NPP) is deemed as a potential risk of stroke; however, recent pieces of evidence showed that calcitonin gene-related peptide is involving in pain progression as well as organ protection. The mechanisms underlying the neuroprotection of calcitonin gene-related peptide are yet poorly described with respect to stroke. The present study showed that the elevated level of calcitonin gene-related peptide-induced by NPP exerts a protective effect against stroke in rats, which was further confirmed in vivo and vitro via mitigation of inflammatory response, inhibition of neuronal cell apoptosis, and increase in regional cerebral blood flow. Repetitive transcranial magnetic stimulation at trigeminal ganglion was performed to simulate to facilitate the release of calcitonin gene-related peptide for a similar neuroprotective effect. Together, these findings posit that the release of calcitonin gene-related peptide-induced by NPP or repetitive transcranial magnetic stimulation protects against stroke in rats. Thus, repetitive transcranial magnetic stimulation could have high application prospects for the prevention and treatment of stroke.

[1]  Yang Xia,et al.  Differential role of adenosine signaling cascade in acute and chronic pain , 2019, Neuroscience Letters.

[2]  M. Lawton,et al.  Global brain inflammation in stroke , 2019, The Lancet Neurology.

[3]  C. Papagno,et al.  Are transcranial brain stimulation effects long-lasting in post-stroke aphasia? A comparative systematic review and meta-analysis on naming performance , 2019, Neuroscience & Biobehavioral Reviews.

[4]  A. Uzdensky Apoptosis regulation in the penumbra after ischemic stroke: expression of pro- and antiapoptotic proteins , 2019, Apoptosis.

[5]  S. Sacco,et al.  CGRP and migraine from a cardiovascular point of view: what do we expect from blocking CGRP? , 2019, The Journal of Headache and Pain.

[6]  S. Maier,et al.  A single peri-sciatic nerve administration of the adenosine 2A receptor agonist ATL313 produces long-lasting anti-allodynia and anti-inflammatory effects in male rats , 2019, Brain, Behavior, and Immunity.

[7]  C. Ayata,et al.  Posterior reversible encephalopathy syndrome in stroke-prone spontaneously hypertensive rats on high-salt diet , 2019, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[8]  R. Dijkhuizen,et al.  Noninvasive Brain Stimulation to Enhance Functional Recovery After Stroke: Studies in Animal Models , 2018, Neurorehabilitation and neural repair.

[9]  R. Cui,et al.  Mechanisms of Transcranial Magnetic Stimulation Treating on Post-stroke Depression , 2018, Front. Hum. Neurosci..

[10]  B. Zhao,et al.  MiR‐377 Regulates Inflammation and Angiogenesis in Rats After Cerebral Ischemic Injury , 2018, Journal of cellular biochemistry.

[11]  S. Bruehl,et al.  Chronic pain-related changes in cardiovascular regulation and impact on comorbid hypertension in a general population: the Tromsø study , 2018, Pain.

[12]  Caiping Wang,et al.  Schisantherin A attenuates ischemia/reperfusion-induced neuronal injury in rats via regulation of TLR4 and C5aR1 signaling pathways , 2017, Brain, Behavior, and Immunity.

[13]  L. Su,et al.  Calcitonin gene-related peptide has protective effect on brain injury induced by heat stroke in rats , 2017, Experimental and therapeutic medicine.

[14]  M. Koike,et al.  Caloric restriction protects livers from ischemia/reperfusion damage by preventing Ca2+‐induced mitochondrial permeability transition , 2017, Free radical biology & medicine.

[15]  P. Pagliaro,et al.  Cardioprotective effects of calcitonin gene-related peptide in isolated rat heart and in H9c2 cells via redox signaling. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[16]  M. D'Esposito,et al.  Reduced brain UCP2 expression mediated by microRNA-503 contributes to increased stroke susceptibility in the high-salt fed stroke-prone spontaneously hypertensive rat , 2017, Cell Death & Disease.

[17]  M. Elkind,et al.  Stroke Risk Factors, Genetics, and Prevention , 2017, Circulation research.

[18]  Á. Chamorro,et al.  Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation , 2016, The Lancet Neurology.

[19]  A. Divani,et al.  Comparisons between Garcia, Modo, and Longa rodent stroke scales: Optimizing resource allocation in rat models of focal middle cerebral artery occlusion , 2016, Journal of the Neurological Sciences.

[20]  S. Benemei,et al.  TRPA1 mediates trigeminal neuropathic pain in mice downstream of monocytes/macrophages and oxidative stress. , 2016, Brain : a journal of neurology.

[21]  J. Montaner,et al.  Impaired Vascular Remodeling after Endothelial Progenitor Cell Transplantation in MMP9-Deficient Mice Suffering Cortical Cerebral Ischemia , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  M. Heger,et al.  Mitochondrial metabolomics unravel the primordial trigger of ischemia/reperfusion injury. , 2015, Gastroenterology.

[23]  J. Borisoff,et al.  Neuropathic Pain, Depression, and Cardiovascular Disease: A National Multicenter Study , 2015, Neuroepidemiology.

[24]  J. Simard,et al.  Targeting secondary injury in intracerebral haemorrhage—perihaematomal oedema , 2015, Nature Reviews Neurology.

[25]  C. Cianchetti,et al.  TRPV1, CGRP and SP in scalp arteries of patients suffering from chronic migraine , 2014, Journal of Neurology, Neurosurgery & Psychiatry.

[26]  S. Brain,et al.  Calcitonin gene-related peptide: physiology and pathophysiology. , 2014, Physiological reviews.

[27]  T. Brzozowski,et al.  Exogenous Asymmetric Dimethylarginine (ADMA) in Pathogenesis of Ischemia-Reperfusion-Induced Gastric Lesions: Interaction with Protective Nitric Oxide (NO) and Calcitonin Gene-Related Peptide (CGRP) , 2014, International journal of molecular sciences.

[28]  J. Nyengaard,et al.  Neuroglobin Over Expressing Mice: Expression Pattern and Effect on Brain Ischemic Infarct Size , 2013, PloS one.

[29]  R. Simon Neuroglobin: Neuroprotection and neurogenesis , 2013, Neuroscience Letters.

[30]  D. Bennett,et al.  Neuroinflammation and the generation of neuropathic pain. , 2013, British journal of anaesthesia.

[31]  E. Walters,et al.  Squid Have Nociceptors That Display Widespread Long-Term Sensitization and Spontaneous Activity after Bodily Injury , 2013, The Journal of Neuroscience.

[32]  Q. Dong,et al.  Decreased Extracellular Adenosine Levels Lead to Loss of Hypoxia-Induced Neuroprotection after Repeated Episodes of Exposure to Hypoxia , 2013, PloS one.

[33]  J. Grau,et al.  Brain-derived neurotrophic factor promotes adaptive plasticity within the spinal cord and mediates the beneficial effects of controllable stimulation , 2012, Neuroscience.

[34]  Zhenzhong Li,et al.  Calcitonin gene-related peptide prevents blood–brain barrier injury and brain edema induced by focal cerebral ischemia reperfusion , 2011, Regulatory Peptides.

[35]  T. Han,et al.  Mechanism of functional recovery after repetitive transcranial magnetic stimulation (rTMS) in the subacute cerebral ischemic rat model: neural plasticity or anti-apoptosis? , 2011, Experimental Brain Research.

[36]  Hsiu-Hsi Chen,et al.  Increased risk of stroke after trigeminal neuralgia – a population-based follow-up study , 2011, Cephalalgia : an international journal of headache.

[37]  Y. Guo,et al.  Protective effects of repetitive transcranial magnetic stimulation in a rat model of transient cerebral ischaemia: a microPET study , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[38]  T. Uchino,et al.  Activation of Sensory Neurons Reduces Ischemia/Reperfusion-induced Acute Renal Injury in Rats , 2009, Anesthesiology.