Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia-Ischemia in Male Rat Pups
| Autor: | Armin Yazdani, Zehra Khoja, Pia Wintermark, Emmanouil Rampakakis, Laura M. Dale, Aaron D. Johnstone |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Sildenafil H&E stain Ischemia Sildenafil Citrate Lateralization of brain function 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Developmental Neuroscience medicine Animals Neurons Neonatal encephalopathy business.industry Neurogenesis Brain Recovery of Function Hypothermia medicine.disease Disease Models Animal 030104 developmental biology Animals Newborn Neurology chemistry Brain Injuries Anesthesia Hypoxia-Ischemia Brain Immunohistochemistry medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Developmental Neuroscience. 38:251-263 |
| ISSN: | 1421-9859 0378-5866 |
| Popis: | Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control. Both groups were randomized to oral sildenafil or vehicle twice daily for 7 consecutive days. Gait analysis was performed on P27. At P30, the rats were sacrificed, and their brains were extracted. The surfaces of both hemispheres were measured on hematoxylin and eosin-stained brain sections. Mature neurons and endothelial cells were quantified near the infarct boundary zone using immunohistochemistry. HI caused significant gait impairment and a reduction in the size of the left hemisphere. Treatment with sildenafil led to an improvement in the neurological deficits as measured by gait analysis, as well as an improvement in the size of the left hemisphere. Sildenafil, especially at higher doses, also caused a significant increase in the number of neurons near the infarct boundary zone. In conclusion, sildenafil administered after neonatal HI may improve brain injury recovery by promoting neuronal populations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|