Related Experiment Video
Updated: Aug 29, 2025
Delivery of In Vivo Acute Intermittent Hypoxia in Neonatal Rodents to Prime Subventricular Zone-derived Neural Progenitor Cell Cultures
Published on: November 2, 2015
Dexmedetomidine alleviates olfactory cognitive dysfunction by promoting neurogenesis in the subventricular zone of
Andi Chen1, Xiaohui Chen1, Jianhui Deng1
1Department of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Insights
Dexmedetomidine (DEX) improves olfactory cognitive dysfunction in neonatal rats with hypoxic-ischemic brain damage (HIBD). DEX promotes neurogenesis and brain-derived neurotrophic factor (BDNF) expression, while reducing neuroinflammation.
Area of Science:
- Neuroscience
- Neonatal Research
- Pharmacology
Background:
- Hypoxic-ischemic brain damage (HIBD) is a primary cause of neonatal neurological dysfunction.
- Olfactory cognitive function is critical for neonatal development and survival.
- Mechanisms of olfactory dysfunction in HIBD and the neuroprotective effects of dexmedetomidine (DEX) require further elucidation.
Purpose of the Study:
- To investigate the efficacy of DEX in improving olfactory cognitive dysfunction in neonatal rats following HIBD.
- To elucidate the underlying mechanisms, including neurogenesis and neuroinflammation, influenced by DEX treatment.
Main Methods:
- HIBD was induced in neonatal rats using the Rice-Vannucci model, followed by immediate DEX administration.
- Brain injury, neurological deficits, and olfactory cognitive function were assessed.
- Neurogenesis in the subventricular zone (SVZ), microglial activation and polarization, and BDNF, TNF-α, IL-1β, and IL-6 levels were evaluated.
Main Results:
- HIBD resulted in significant brain infarction, neurological deficits, and impaired olfactory cognition.
- DEX treatment markedly improved olfactory cognitive function and neurological deficits in HIBD rats.
- DEX increased neurogenesis in the SVZ by upregulating BDNF expression and modulated microglial polarization, suggesting reduced neuroinflammation.
Conclusions:
- DEX administration effectively ameliorates olfactory cognitive dysfunction in neonatal rats suffering from HIBD.
- The neuroprotective effects of DEX are associated with the promotion of SVZ neurogenesis and BDNF expression.
- DEX may exert its benefits by inhibiting neuroinflammation and promoting M1 to M2 microglial polarization.
Abstract:
Background: Hypoxic-ischemic brain damage (HIBD) is the main cause of neurological dysfunction in neonates. Olfactory cognitive function is important for feeding, the ability to detect hazardous situations and social relationships. However, only a few studies have investigated olfactory cognitive dysfunction in neonates with HIBD; furthermore, the specific mechanisms involved are yet to be elucidated. It has been reported that neurogenesis in the subventricular zone (SVZ) is linked to olfactory cognitive function. Recently, dexmedetomidine (DEX) has been shown to provide neuroprotection in neonates following HIBD. In the present study, we investigated whether DEX could improve olfactory cognitive dysfunction in neonatal rats following HIBD and attempted to determine the underlying mechanisms. Methods: We induced HIBD in rats using the Rice-Vannucci model, and DEX (25 μg/kg, i.p.) was administered immediately after the induction of HIBD. Next, we used triphenyl tetrazolium chloride (TTC) staining and the Zea-longa score to assess the success of modelling. The levels of BDNF, TNF-α, IL-1β and IL-6 were determined by western blotting. Immunofluorescence staining was used to detect microglial activation and microglial M1/M2 polarization as well as to evaluate the extent of neurogenesis in the SVZ. To evaluate the olfactory cognitive function, the rats in each group were raised until post-natal days 28-35; then, we performed the buried food test and the olfactory memory test. Results: Analysis showed that HIBD induced significant brain infarction, neurological deficits, and olfactory cognitive dysfunction. Furthermore, we found that DEX treatment significantly improved olfactory cognitive dysfunction in rat pups with HIBD. DEX treatment also increased the number of newly formed neuroblasts (BrdU/DCX) and neurons (BrdU/NeuN) in the SVZ by increasing the expression of BDNF in rat pups with HIBD. Furthermore, analysis showed that the neurogenic effects of DEX were possibly related to the inhibition of inflammation and the promotion of M1 to M2 conversion in the microglia. Conclusion: Based on the present findings, DEX treatment could improve olfactory cognitive dysfunction in neonatal rats with HIBD by promoting neurogenesis in the SVZ and enhancing the expression of BDNF in the microglia. It was possible associated that DEX inhibited neuroinflammation and promoted M1 to M2 conversion in the microglia.
