Abstract
Brain ischemia leads to poor oxygen supply, and is one of the leading causes of brain damage and/or death. Neuroprotective agents are thus in great need for treatment purpose. Using both young and aged primary cultured hippocampal neurons as in vitro models, we investigated the effect of sodium hydrosulfide (NaHS), an exogenous donor of hydrogen sulfide, on oxygen-glucose deprivation (OGD) damaged neurons that mimick focal cerebral ischemia/reperfusion (I/R) induced brain injury. NaHS treatment (250 μM) protected both young and aged hippocampal neurons, as indicated by restoring number of primary dendrites by 43.9 and 68.7%, number of dendritic end tips by 59.8 and 101.1%, neurite length by 36.8 and 66.7%, and spine density by 38.0 and 58.5% in the OGD-damaged young and aged neurons, respectively. NaHS treatment inhibited growth-associated protein 43 downregulation, oxidative stress in both young and aged hippocampal neurons following OGD damage. Further studies revealed that NaHS treatment could restore ERK1/2 activation, which was inhibited by OGD-induced protein phosphatase 2 (PP2A) upregulation. Our results demonstrated that NaHS has potent protective effects against neuron injury induced by OGD in both young and aged hippocampal neurons.
Highlights
Stroke is one of the leading causes of senior adult disability and death worldwide (Martin et al, 2005)
Hippocampal neurons derived from aged rats showed more severe impairments than their young counterparts (Figures 1A,B), suggesting hippocampal neurons derived from aged rats were more vulnerable
In addition to MTT assay, we performed the Lactate Dehydrogenase (LDH) release assay, a widely used enzymatic assay to assess cytotoxicity, and the results were consistent with our MTT assay, indicating that NaHS was able to protect the hippocampal neurons from oxygen-glucose deprivation (OGD)-induced cell damage (Figure 1C)
Summary
Stroke is one of the leading causes of senior adult disability and death worldwide (Martin et al, 2005). Stroke is commonly caused by either interrupted or reduced blood supply to the brain such as ischemia, thereby leaving brain cells in a oxygen-glucose deprivation (OGD) condition. Ischemia/reperfusion (I/R) induced oxidative stress, caused by impaired metabolism in the brain cells, is believed to be the one of the major contributors to brain I/R injury (Zeiger et al, 2009; Ma et al, 2015). There is an urgent need to search for promising neuroprotective agents, that could better protect ischemic neurons in the brain These new agents should prevent irreversible brain injury with minimal side effects, especially in the aged population, because IPC is more detrimental in the aged brain (Choe et al, 2009)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
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 call