Abstract
BackgroundExploring the effective therapy for neonatal hypoxic-ischemic brain injury is an important goal. This study was designed to investigate how dexmedetomidine (DEX) contribute to hypoxic brain injury.MethodsDeveloping Sprague-Dawley rat models of hypoxia/reoxygenation (H/R) injury were constructed to simulate neonatal hypoxic brain injury for DEX treatment. Immunohistochemistry and western blot were performed to measure neuroglobin (Ngb) protein expression in hippocampal tissues. Hippocampal neuron injury and apoptosis were detected by Nissl staining and TUNEL assay, respectively. A Morris water maze (MWM) test was performed to evaluate the long-term learning and memory function.ResultsThe expression of Ngb was increased following H/R model establishment and up-regulated by medium and high doses of DEX, but not up-regulated by low doses of DEX. Medium and high doses of DEX alleviated the H/R injury as well as induced the reduction of Nissl bodies and apoptosis. Besides, medium and high doses of DEX down-regulated cytosolic Cyt-c, Apaf-1, and caspase-3 in H/R injury model. MWM test showed that medium and high doses of DEX significantly shortened the escape latency and enhanced the number of platform crossings. However, low doses of DEX have no effect on Nissl bodies, mitochondrial apoptosis, expression of apoptosis-related proteins and long-term learning functions.ConclusionsDEX induced Ngb expression in H/R rat models. The neuroprotection of DEX-mediated Ngb up-regulation may be achieved by inhibiting neuronal apoptosis through the mitochondrial pathway. Findings indicated that DEX may be useful as an effective therapy for neonatal hypoxic brain injury.
Highlights
Neonatal hypoxic-ischemic (H/I) brain injury is a frequently encountered clinical problem in survivors of perinatal asphyxia, which is associated with mortality and neurodevelopmental morbidity (Cheng et al, 1997)
DEX Mediates the Up-Regulation of Ngb in H/R Injury To evaluate the effects of DEX on Ngb expression, the expression levels of Ngb in hippocampal tissue were analyzed at different times using IHC and western blot, respectively
IHC analysis showed that the Ngb expression was up-regulated in H/R injury rat model at each time point compared to the control (Figure 1A)
Summary
Neonatal hypoxic-ischemic (H/I) brain injury is a frequently encountered clinical problem in survivors of perinatal asphyxia, which is associated with mortality and neurodevelopmental morbidity (Cheng et al, 1997). Due to the selective regional and cellular vulnerability, it usually presents different outcomes in neonates (Cowan et al, 2003). Neonatal H/I cerebral injury often caused multiple adverse neurologic outcomes, including cognitive disorder, epilepsy, cerebral palsy, and mental retardation (van Handel et al, 2007). There is currently no effective therapy for neonatal H/I cerebral injury (Perlman, 2006). Exploring the therapeutic targets and effective therapies for the H/I brain injury is an important goal in clinical. Exploring the effective therapy for neonatal hypoxic-ischemic brain injury is an important goal. This study was designed to investigate how dexmedetomidine (DEX) contribute to hypoxic brain injury
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