Endothelial proliferation modulates neuron-glia survival and differentiation in ischemic stress

Recent studies have shown that endothelial proliferation and angiogenic response are characteristic of degenerative events, such that the magnitude of endothelial activation is reflective of the progression of neurodegeneration.

We conclude that neuronal degeneration in cyanide toxicity or vascular occlusion is dependent on an increase in endothelial proliferation (↑CD31), glia activation (↑GFAP) and a decrease in monocyte expression (↓CD45); representing a pro-inflammatory response. Furthermore, cyanide toxicity induced more prominent degenerative changes when compared with the vascular occlusion due to a higher CD31/GFAP expression. Subsequent withdrawal of the ischemia facilitated a reduction in GFAP/CD31 with a corresponding increase in monocytes (↑CD45) for vascular remodeling and neurosurvival. The VO-I showed a significant increase in vascular remodelling than the CN-I due to a more significant increase in monocytic expression (CD45) after the withdrawal of the occlusion. Generally, we found that degeneration was prominent in the parietal cortex and less in the periventricular zone for both forms of ischemia.

Global vascular occlusion (VO) and cyanide toxicity (CN) were induced in separate sets of male adult wistar rats for 10 days (treatment phase). Subsequently, the treatment was discontinued for another 10 days (withdrawal phase) (CN-I and VO-I). A separate group of control was maintained for 10 days and received normal saline for this duration. The animals were euthanized at day 10 (treatment and control) and day 20 (withdrawal) after which the tissue was processed for antigen retrieval immunohistochemistry to demonstrate; H&E (general histology) CD31/PECAM 1(endothelial proliferation), CD45 (monocyte/phagocyte), GFAP (glia), NSE (neuron), Ki-67 (cell proliferation) and NF (neurofilament). Total cell count, immunopositive cell counts, arterial wall thickness and lumen width were determined and plotted using ANOVA with significance set at P<0.05*.

This study sets out to, compare, the degenerative changes seen in the parietal cortex (PC) and periventricular zone (PVZ) after cyanide toxicity or vascular occlusion.

We observed an increase in endothelial proliferation (↑CD31), glia activation and a decrease in neuron count in vascular occlusion and cyanide toxicity after the treatment phase (degeneration). The neuron count increased (↑NSE) after withdrawal of cyanide treatment and vascular occlusion and was accompanied by a corresponding decrease in endothelial and glia activation (↓CD31/GFAP). Degenerative changes were more prominent in cyanide toxicity when compared with vascular occlusion. The increase in CD45 expression coupled with a reduced CD31/GFAP after the withdrawal phase was evident of vascular remodeling and neurosurvival.