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Metyrapone prevents acute glucose hypermetabolism and short-term brain damage induced by intrahippocampal administration of 4-aminopyridine in rats
| Content Provider | Semantic Scholar |
|---|---|
| Author | García-García, L. Rosa, Rubén Fernández De La Delgado, Mercedes Silván, A. M. Alvarez Pozo, Miguel A. |
| Copyright Year | 2018 |
| Abstract | &NA; Intracerebral administration of the potassium channel blocker 4‐aminopyridine (4‐AP) triggers neuronal depolarization and intense acute seizure activity followed by neuronal damage. We have recently shown that, in the lithium‐pilocarpine rat model of status epilepticus (SE), a single administration of metyrapone, an inhibitor of the 11&bgr;‐hydroxylase enzyme, had protective properties of preventive nature against signs of brain damage and neuroinflammation. Herein, our aim was to investigate to which extent, pretreatment with metyrapone (150 mg/kg, i.p.) was also able to prevent eventual changes in the acute brain metabolism and short‐term neuronal damage induced by intrahippocampal injection of 4‐AP (7 &mgr;g/5 &mgr;l). To this end, regional brain metabolism was assessed by 2‐deoxy‐2‐[18F]fluoro‐D‐glucose ([18F]FDG) positron emission tomography (PET) during the ictal period. Three days later, markers of neuronal death and hippocampal integrity and apoptosis (Nissl staining, NeuN and active caspase‐3 immunohistochemistry), neurodegeneration (Fluoro‐Jade C labeling), astrogliosis (glial fibrillary acidic protein (GFAP) immunohistochemistry) and microglia‐mediated neuroinflammation (in vitro [18F]GE180 autoradiography) were evaluated. 4‐AP administration acutely triggered marked brain hypermetabolism within and around the site of injection as well as short‐term signs of brain damage and inflammation. Most important, metyrapone pretreatment was able to reduce ictal hypermetabolism as well as all the markers of brain damage except microglia‐mediated neuroinflammation. Overall, our study corroborates the neuroprotective effects of metyrapone against multiple signs of brain damage caused by seizures triggered by 4‐AP. Ultimately, our data add up to the consistent protective effect of metyrapone pretreatment reported in other models of neurological disorders of different etiology. |
| Starting Page | 92 |
| Ending Page | 106 |
| Page Count | 15 |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.neuint.2017.11.018 |
| PubMed reference number | 29203398 |
| Journal | Medline |
| Volume Number | 113 |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0197018617304862 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0197018617304862?dgcid=api_sd_search-api-endpoint |
| Alternate Webpage(s) | https://doi.org/10.1016/j.neuint.2017.11.018 |
| Journal | Neurochemistry International |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
