Effect of Vascular Endothelial Growth Factor (VEGF) on Neuronal and Glial Response Following Transient Global Ischemia in Rats

Son, Byung Chul; Lee, Mun Yong; Park, Chun Kun; Chun, Myung Hoon; Kang, Joon Ki

Abstract

OBJECTIVE
The authors present the effect of VEGF upon neuronal and glial response following transient global ischemia of the rat
METHODS
We studied the effect of VEGF in 36 rats subjected to 15 minutes of transient global ischemia. Animals were devided into control group(transient global ischemia only: day-3, day-7, day-14, respectively n=6) and VEGF-treated group(transient global ischemia with intraventricular injection of 100 micro gram VEGF: day-3, day-7, day-14, respectively n=6). These animals were sacrificed at 3 days, 7 days and 14 days after induction of ischemia. Nissle stain and immunohistochemistry of GFAP(glial fibrillary acidic protein), OX-42, and ED1 were done for assessment of neuronal and glial responses.
RESULTS
In the CA1 hippocampus, there was a significant reduction of pyramidal cell damage in VEGF-treated group as compared with control group in post-ischemia 3, 7, 14 days(p<0.05). In the CA3 hippocampus which is relatively resistant to ischemia, reduction of pyramidal cell damage was significant in post-ischemia 7 days(p<0.05), not significant in post-ischemia 3, 14 days(p>0.05). In the assessment of CA1 hippocampus with GFAP stained areas, there was significant reduction of reactivity in post-ischemia 3, 7 days(p<0.05), not significant in post-ischemia 14 days(p>0.05). In the CA3 hippocampus, reduction of GFAP reactivity was significant in post-ischemia 3, 7 days(p<0.05), not significant in post-ischemia 14 days(p>0.05). In the assessment of CA1 hippocampus with OX-42 stained areas, there was significant reduction of reactivity in post-ischemia 3, 7, 14 days(p<0.05). But in the CA3 hippocampus, the difference was not significant in post-ischemia 3, 7 days(p<0.05). In the assessment of of CA1 hippocampus with ED1 stained areas, there was significant reduction of reactivity in post-ischemia 3, 7, 14 days(p<0.05). But in the CA3 hippocampus, the difference was significant in post-ischemia 3 days only(p<0.05).
CONCLUSION
These results suggest that VEGF can reduce neuronal damage in transient global ischemia, thus have protective effect on ischemic brain injury. In our experiment, the reduction of glial response with VEGF seems to be related to the secondary neuroprotective effect of VEGF. However, the proliferation of endothelial cells and new vessel formation take days to months, the thus neuroprotective effect of VEGF against ischemia seems to related to a certain mechanism rather than angiogenesis.