Abstract
Co-treatment of neuroprotective reagents may improve the therapeutic efficacy of hypothermia in protecting neurons during ischemic stroke. This study aimed to find promising drugs that enhance the neuroprotective effect of mild hypothermia (MH). 26 candidate drugs were selected based on different targets. Primary cultured cortical neurons were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) to induce neuronal damage, followed by either single treatment (a drug or MH) or a combination of a drug and MH. Results showed that, compared with single treatment, combination of MH with brain derived neurotrophic factor, glibenclamide, dizocilpine, human urinary kallidinogenase or neuroglobin displayed higher proportion of neuronal cell viability. The latter three drugs also caused less apoptosis rate in combined treatment. Furthermore, co-treatment of those three drugs and MH decreased the level of reactive oxygen species (ROS) and intracellular calcium accumulation, as well as stabilized mitochondrial membrane potential (MMP), indicating the combined neuroprotective effects are probably via inhibiting mitochondrial apoptosis pathway. Taken together, the study suggests that combined treatment with hypothermia and certain neuroprotective reagents provide a better protection against OGD/R-induced neuronal injury.
Highlights
Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury
This study aimed to find promising drugs that enhance the neuroprotective effect of mild hypothermia (MH). 26 candidate drugs were selected based on different targets
oxygen-glucose deprivation and reoxygenation (OGD/R) induced a dramatic reduction of cell viability proportion (CVP), while treatment of MH or six drugs, including Alb, brain derived neurotrophic factor (BDNF), GBC, human urinary kininogenase (HUK) MK801 and Ngb, significantly recovered CVP (P,0.05)
Summary
Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury. I schemic stroke is one of the most common diseases that cause death and disability worldwide, which brings a hard burden to families and society It starts with sudden cessation of blood flow, oxygen, glucose and energy in the lesion area, followed by series of pathologic cascading events including exitotoxicity, calcium influx, free radicals accumulation, inflammation response, blood-brain barrier breakdown, edema, cell death and so on[1,2]. Oxygen-glucose deprivation and reoxygenation (OGD/ R) was used to induce the neuronal injury model in primary cultured cortical neurons to mimic the brain ischemia in vitro. With this model, we compared the neuroprotective effects of the 26 candidate medicines with or without MH. Among them, compared with single treatment, HUK, MK-801 or Ngb were shown to have better protective effects in combination with hypothermia against OGD/Rinduced neuronal damage
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
