Insulin-like growth factor-1 inhibits spreading depression-induced trigeminal calcitonin gene related peptide, oxidative stress & neuronal activation in rat
| Autor: | Richard P. Kraig, Lisa Won |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty business.industry General Neuroscience Calcitonin gene-related peptide medicine.disease_cause medicine.disease 03 medical and health sciences Trigeminal ganglion 030104 developmental biology 0302 clinical medicine Endocrinology Nociception Migraine Calcitonin Cortical spreading depression Internal medicine medicine Neurology (clinical) business Receptor Molecular Biology 030217 neurology & neurosurgery Oxidative stress Developmental Biology |
| Zdroj: | Brain Research. 1732:146673 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2020.146673 |
| Popis: | Migraineurs can show brain hyperexcitability and oxidative stress that may promote headache. Since hyperexcitability can enhance oxidative stress which promotes hyperexcitability, ending this feed-back loop may reduce migraine. Neocortical spreading depression, an animal model of migraine begins with hyperexcitability and triggers oxidative stress in the neocortical area involved and in the trigeminal system, which is important to pain pathway nociceptive activation in migraine. Additionally, oxidative stress causes increased trigeminal ganglion calcitonin gene-related peptide release and oxidative stress can reduce spreading depression threshold. Insulin-like growth factor-1 significantly protects against spreading depression in vitro by reducing oxidative stress and it is effective against spreading depression after intranasal delivery to animals. Here, we used adult male rats and extend this work to study the trigeminal system where insulin-like growth factor-1 receptors are highly expressed. Recurrent neocortical spreading depression significantly increased surrogate markers of trigeminal activation - immunostaining for trigeminal ganglion oxidative stress, calcitonin gene related peptide levels and c-fos in the trigeminocervical complex versus sham. These effects were significantly reduced by intranasal delivery of insulin-like growth factor-1 a day before recurrent neocortical spreading depression. Furthermore, intranasal treatment with insulin-like growth factor-1 significantly reduced naive levels of trigeminal ganglion calcitonin gene related peptide versus sham with no impact on blood glucose levels. Intranasal delivery of insulin-like growth factor-1 not only mitigates neocortical spreading depression, a cause of migraine hyperexcitability modeled in animals, but also when neocortical spreading depression is triggered by supra-threshold stimuli, insulin-like growth factor-1 effectively reduces nociceptive activation in the trigeminal system. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect