Abstract 2259: Age-related Increases In Microvascular Phosphodiesterase 4d Expression And Perimicrovascular Space Following Transient Global Ischemia In Rats
Background and purpose. While a majority of clinical genomic studies indicate that the gene encoding phosphodiesterase 4D (PDE4D) increases risk of cerebral ischemia, the role of PDE4D in the actual pathogenic mechanisms of ischemia remains unclear. The present study attempts to define a role for PDE4D in the acute phase of cerebral ischemia by monitoring changes in microvascular PDE4D expression and changes in the inside bore of the microvasculature in young and aged rats.
Methods. Male F344 rats aged 4- and 24-months were subjected to sham surgery (n=4/group): young control (YC) and aged control (AC) groups or transient global ischemia: young ischemia (YI, n=7) and aged ischemia (AI, n=8) groups. Histological assessments and measurements of PDE4D immunoreactivity in the hippocampus were performed 8 days following ischemia.
Results. Perivascular tissue density (defined by an index of the intensity of weak positive per square micron) was significantly lower in the AC group than in the YC group (p<0.05, Fig. 1E). Transient global ischemia elicited a significant decrease in tissue density in the perimicrovascular space in both young and aged animals as compared to controls (Fig. 1E). In addition, internal bore circumference and cross-sectional area increased dramatically as a result of ischemia (Fig. 1F). Ischemia also caused a severe loss of hippocampal CA1 neurons (Fig. 2A,B,C) in association with significant increases in PDE4D immunoreactivities (Fig. 2D-F). Interestingly, hippocampal neuron loss following ischemia paralleled PDE4D expression in microvessels: cell loss was accompanied by much higher levels of perivascular PDE4D expression with this effect being greater in the younger animals.
In conclusion, decreases in perivascular tissue density and enlargements in microvascular bore likely indicate an increase in brain-blood barrier (BBB) permeability following the onset of ischemia. This is associated with an increased expression of PDE4D. Increased PDE4D expression following cerebral ischemia may play a role in changing BBB permeability and, thus, secondarily affect ischemic outcome.
- © 2012 by American Heart Association, Inc.