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2-Vessel Occlusion/Hypotension: A Rat Model of Global Brain Ischemia
Published on: June 22, 2013
Cell death in the choroid plexus following transient forebrain global ischemia in the rat
1Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University Hospital, 221 85, Lund, Sweden. Mikael.Ferrand_Drake@expbr.lu.se
Insights
Cerebral ischemia causes delayed neuronal death in CA1 neurons. Our study reveals choroid plexus cell death precedes this, potentially disrupting the blood-CSF barrier and impacting neuronal survival.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Cerebral ischemia leads to delayed neuronal death (DND) in CA1 pyramidal neurons, typically occurring around 48 hours post-insult.
- The precise mechanisms regulating this delayed cell death remain incompletely understood, with a focus on intrinsic neuronal factors.
Purpose of the Study:
- To investigate potential extrinsic mechanisms contributing to delayed neuronal death in CA1 pyramidal neurons following transient forebrain global ischemia.
- To explore the role of choroid plexus cell death in the context of cerebral ischemia and its potential impact on neuronal survival.
Main Methods:
- Induction of transient forebrain global ischemia in a rodent model.
- Assessment of cell death in the hippocampus (CA1 region) and choroid plexus using TUNEL staining.
- Determination of the temporal profile of cell death in both regions during the recovery period.
Main Results:
- Significant TUNEL-positive cell death was observed in the choroid plexus at 18, 24, and 36 hours post-ischemia.
- Choroid plexus cell death preceded the absence of TUNEL-positive cells in the CA1 region at 24 hours.
- No TUNEL-positive cells were detected in the CA1 region at 24 hours post-ischemia.
Conclusions:
- Cell death in the choroid plexus occurs earlier than delayed neuronal death in CA1 pyramidal neurons following transient forebrain global ischemia.
- Choroid plexus cell death may compromise the blood-cerebrospinal fluid barrier, allowing harmful substances to enter the brain parenchyma.
- These findings suggest that choroid plexus integrity is crucial for CA1 neuron survival and may represent a therapeutic target in ischemic stroke.
Abstract:
Following a complete disruption of blood flow to the brain, cerebral ischemia, a specific neuronal population, namely the CA1 pyramidal neurons in the hippocampus, will die a delayed type of cell death. This is often referred to as "delayed neuronal death" (DND). It is not known why it takes around 48 hours for these cells to die. It is very often speculated that events, intrinsic to the CA1 neurons, regulate their demise, whereas it is less often considered that extrinsic mechanisms also could play an important role for the development of DND. We discovered that in addition to the CA1 pyramidal neurons, cells in the choroid plexus were TUNEL (terminaldeoxynucleotidyl-mediated biotin-dUTP nick-end labeling)-positive following transient forebrain global ischemia. The time course and the number of TUNEL-positive cells were determined. A dramatic increase in the number of TUNEL-positive cells in the choroid plexus was seen at 18, 24, and at 36 hours of recovery, but not at 48 hours of recovery following 15 minutes of transient forebrain global ischemia. No TUNEL-positive cells were seen at 24 hours of recovery in the CA1 region. The cell death in the choroid plexus thus preceded the occurrence of cell death in the CA1 region. Massive cell death in the choroid plexus will inevitably lead to a leaky blood-CSF barrier, which in turn will allow substances to enter the ventricular system and from there reach the brain parenchyma. We, therefore, conclude that choroid plexus cell death may adversely affect the outcome of CA1 pyramidal neurons following transient forebrain global ischemia, through, e.g., a disruption of the blood-cerebro spinal fluid barrier. Alternatively, the choroid plexus may produce factors, which can affect the outcome of neurons.
