Abstract
Among all the brain, the hippocampus is the most susceptible region to ischemic lesion, with the highest vulnerability of CA1 pyramidal neurons to ischemic damage. This damage may cause either prompt neuronal death (within hours) or with a delayed appearance (over days), providing a window for applying potential therapies to reduce or prevent ischemic impairments. However, the time course when ischemic damage turns to neuronal death strictly depends on experimental modeling of cerebral ischemia and, up to now, studies were predominantly focused on a short time-window—from hours to up to a few days post-lesion. Using different schemes of oxygen-glucose deprivation (OGD), the conditions taking place upon cerebral ischemia, we optimized a model of mimicking ischemic conditions in organotypical hippocampal slices for the long-lasting assessment of CA1 neuronal death (at least 3 weeks). By combining morphology and electrophysiology, we show that prolonged (30-min duration) OGD results in a massive neuronal death and overwhelmed astrogliosis within a week post-OGD whereas OGD of a shorter duration (10-min) triggered programmed CA1 neuronal death with a significant delay—within 2 weeks—accompanied with drastically impaired CA1 neuron functions. Our results provide a rationale toward optimized modeling of cerebral ischemia for reliable examination of potential treatments for brain neuroprotection, neuro-regeneration, or testing neuroprotective compounds in situ.
Highlights
Cerebral ischemia is the disease that causes the highest mortality or severe disability in patients of various ages
In a similar tissue preparation, mild oxygen-glucose deprivation (OGD) (10-min duration) triggered a programmed CA1 neuronal death with a delayed appearance that was associated with impairments in CA1 neuron function observed from week 1 post-OGD
Various experimental models for mimicking cerebral ischemia in vivo, in vitro, or in situ to elucidate the mechanisms of ischemic damage and possible neuroprotection, the organotypic slice cultures have been often a subject of preference (Tasca et al, 2015)
Summary
Cerebral ischemia is the disease that causes the highest mortality or severe disability in patients of various ages. The ischemia-induced death of CA1 neurons results in memory loss (Xu et al, 2016) and severe cognitive disorders (Morán et al, 2017) that may develop shortly or with a delayed appearance following insult. Different experimental models have been developed aimed to elucidate the mechanisms of this phenomenon and possible neuroprotection against ischemic damage, those vary by managing of simulating cerebral ischemia in vivo, in situ, or in vitro as well as by a duration of ischemic conditions. A model of mimicking ischemic conditions in organotypic hippocampal slice cultures is the one that yields long-lasting assessment of CA1 ischemic damage using oxygen-glucose deprivation (OGD), the conditions taking place under transient ischemic insult, to perfectly simulate ischemic excitotoxicity in situ (Tasca et al, 2015). A capability for the feasibly applied combinations of molecular and genetic approaches makes organotypic slice cultures perfectly suited for studying the precise mechanisms of post-ischemic tissue damage (Cho et al, 2004; Bonde et al, 2005; Chip et al, 2013)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
