Dexmedetomidine Alleviates Neurogenesis Damage Following Neonatal Midazolam Exposure in Rats through JNK and P38 MAPK Pathways

Abstract

Midazolam, a widely used anesthetic, inhibits proliferation of neural stem cells (NSCs) and induces neuroapoptosis in neonates. Dexmedetomidine, an effective auxiliary medicine in clinical anesthesia, protects the developing brain against volatile anesthetic-induced neuroapoptosis. Whether dexmedetomidine protects against neurogenesis damage induced by midazolam remains unknown. This study aims to clarify the protective effect of dexmedetomidine on midazolam-induced neurogenesis damage and explore its potential mechanism. Postnatal 7-day-old Sprague–Dawley (SD) rats and cultured NSCs were treated with either normal saline, midazolam, or dexmedetomidine combined with midazolam. The rats were sacrificed at 1, 3, and 7 days after treatment. Cell proliferation was assessed by 5-bromodeoxyurdine (BrdU) incorporation. Cell viability was determined using MTT assay. Cell differentiation and apoptosis were detected by immunofluorescent staining and terminal dUTP nick-end labeling (TUNEL), respectively. The protein levels of p-JNK, p-P38, and cleaved caspase-3 were quantified using Western blotting. Midazolam decreased cell proliferation and increased cell apoptosis in the subventricular zone (SVZ), the subgranular zone (SGZ) of the hippocampus, and cultured NSCs. Moreover, midazolam decreased cell viability and increased the expression of p-JNK and p-P38 in cultured NSCs. Co-treatment with dexmedetomidine attenuated midazolam-induced changes in cell proliferation, viability, apoptosis, and protein expression of p-JNK and p-P38 in cultured NSCs. Midazolam and dexmedetomidine did not affect the differentiation of the cultured NSCs. These results indicate that dexmedetomidine alleviated midazolam-induced neurogenesis damage via JNK and P38 MAPK pathways.

Analgesic effect of dexmedetomidine in rats after chronic constriction injury by mediating microRNA‐101 expression and the E2F2–TLR4–NF‐κB axis

“…Besides, Dex administration decreased expression levels of pro‐inflammatory factors (IL‐6, IL‐8, TNF‐α), thus lowering the neuroinflammatory response to sevoflurane (Wang & Wang, 2019). Dex improved neurogenesis damage evoked by midazolam in subventricular zone and subgranular zone (Lei et al., 2020). Therefore, we postulated that Dex might regulate neuroinflammation and neuron apoptosis in NPP.…”

Biomimetic Melanosomes Promote Orientation-Selective Delivery and Melanocyte Pigmentation in the H2O2-Induced Vitiligo Mouse Model

“…To confirm the enhanced cell viability corresponding to newly formed cells and to elucidate the potential role of KPV in cell proliferation, PIG1 cells labeled with anti-BrdU were employed to visualize newly proliferated cells. 51 As shown in Figure 3e,f, Lipo treatment generated a small increase in the percentage of proliferated cells, as reflected by a sparse red fluorescence signal. In contrast to the Lipo group, the number of cells in the KPV+Lipo group dramatically increased.…”

“…The biochemical reactions catalyzed by TRP-1 and TRP-2 are key steps in the synthesis of melanin. , Both the KPV-Lipo and KPV+Lipo treatments clearly upregulated TYR, TRP1 and TRP2 protein expression (Figure d and Figure S6). To confirm the enhanced cell viability corresponding to newly formed cells and to elucidate the potential role of KPV in cell proliferation, PIG1 cells labeled with anti-BrdU were employed to visualize newly proliferated cells . As shown in Figure e,f, Lipo treatment generated a small increase in the percentage of proliferated cells, as reflected by a sparse red fluorescence signal.…”

Dexmedetomidine: An Alternative to Pain Treatment in Neonatology

“…Another potential benefit that has been widely studied is neuroprotection, which makes this treatment an ideal option for the neonatal patient, especially preterm neonates, who are the most vulnerable to the neurodevelopmental effects of the molecules that are traditionally used in sedoanalgesia [ 70 , 71 , 72 ]. This neuroprotective function has been proven in several preclinical studies of injury models including ischemia-reperfusion, inflammation, and traumatic brain injury as well as adult clinical trials of brain trauma [ 73 , 74 ].…”