Abstract TMP70: Reduced Hippocampal Synapses Underlie Loss of Long-Term Potentiation after Experimental Subarachnoid Hemorrhage
Background: Patients who survive aneurysmal subarachnoid hemorrhage (SAH) often have deficits in learning, memory and executive function, although structural brain damage may not be detectable. We previously reported that rodents with SAH develop cognitive deficits and loss of long-term potentiation (LTP), a probable electrophysiological correlate of learning and memory. We hypothesize that loss of LTP may be caused by diminished synapses and/or dysfunction of synaptic molecules responsible for LTP, and that this occurs without neuronal death.
Methods: SAH was created by injection of 300 μl of fresh, unheparinized arterial blood into the prechiasmatic cistern of Sprague-Dawley rats (300-350g). Controls were injected with the same amount of saline. Cell death was detected with Fluoro-jade B and TUNEL staining. The number of synapses in dendritic layer of CA1 was quantified by double immunohistochemical staining of MAP2 and synaptophysin, or directly by transmission electron microscopy. Glutamate receptor subunits (GluR1/2) and CaM kinase II were quantified by immunohistochemical staining. Superoxide and nitric oxide (NO) concentrations in freshly homogenized hippocampal tissues were detected by spectrophotometry with DAF-2DA and MCLA dyes.
Results: In the dendritic area of CA1, the number of synapses was significantly decreased after SAH compared to controls (54±4/image for SAH, 74±3 for controls, p<0.001). Similarly, the expression of GluR1, GluR2 and CaM kinase II was decreased in SAH rats. Decreased superoxide (0.038±0.006 for SAH, 0.059±0.01 for control p<0.001) but increased NO was detected in rats with SAH as compared to controls (1251±118 for SAH, 518±118 for controls, p<0.001). Fluoro-jade B and TUNEL staining disclosed no to minimal CA1 cell death.
Conclusions: Loss of LTP after SAH in rats may be due to a synaptic plasticity rather than cell death. Decreased immunoreactivity to GluR1, GluR2 and CaM kinase II suggests reduction in key proteins that mediator LTP may also contribute. Decreased superoxide and increased NO suggest oxidative stress is involved in the loss of LTP.
- © 2012 by American Heart Association, Inc.