Dexmedetomidine alleviates olfactory cognitive dysfunction by promoting neurogenesis in the subventricular zone of hypoxic-ischemic neonatal rats

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.

The Impact of Dexmedetomidine Doses on Postoperative Cognitive Dysfunction and Inflammatory Response in Elderly Female Patients Undergoing Laparoscopic Cholecystectomy

“…Dex also possesses certain anti-in ammatory properties [18] and can reduce stress responses and protect cognitive function by inhibiting in ammatory reactions, effectively preventing the occurrence of POCD [19]. This effect may be related to two mechanisms: (1) Dex can inhibit the sympathetic nervous system by acting on α2-adrenergic receptors, thereby reducing stress and in ammatory responses [20]; and (2) Dex may reduce the expression of in ammatory factors by inhibiting certain signaling pathways [21][22]. Pro-in ammatory factors such as TNF-α, IL-1β, and the anti-in ammatory factor IL-10 are major in ammatory markers during the perioperative period, and their expression levels can re ect the severity of the in ammatory response.…”

Dexmedetomidine alleviates cognitive impairment by promoting hippocampal neurogenesis via BDNF/TrkB/CREB signaling pathway in hypoxic–ischemic neonatal rats

“…Western blot analysis was performed as described previously 7,24 . The hippocampal tissues were collected at 1, 2, 3, 7, and 14 days after HI insults and immediately placed on ice.…”

“…The immunofluorescence analysis was conducted as previously described 24 . The brain tissues were collected and fixed in paraformaldehyde overnight at 4°C.…”

“…The neonatal rats were divided into three groups: (1) the sham group, (2) the HI group, and (3) the HI + DEX group: The HIBD model rats were treated with DEX (25 μg/kg, Sigma‐Aldrich) via intraperitoneally injection immediately after HI insults. This dosage and mode of administration were chosen based on the findings of our previous studies on the neuroprotective effects of DEX 6,24 . We measured the expression levels of BDNF/TrkB/CREB pathway‐related proteins, observed changes in astrocytes phenotype, and assessed hippocampal neurogenesis.…”

The Role of BDNF as a Biomarker in Cognitive and Sensory Neurodegeneration

“…M1 microglia aggravate brain injury and impede the repair of the CNS by producing pro-inflammatory factors (IL-6 and IL1-β), whereas M2 microglia promotes the repair of neural damage and the survival of brain cells by releasing anti-inflammatory factors (IL-10 and IL-4) and some neurotrophic factors including BDNF. This factor promotes neuronal growth, reduces the loss of neurons, and promotes neurogenesis as well, thus highlighting the importance of BDNF in the repair of neurological damage [290].…”