Background: Oxidative stress has been implicated as a causative agent for most neurodegenerative diseases especially for itsability to induce neuronal degeneration and cell death. Recent studies have shown that endothelial proliferation and angiogenic response are characteristic of these degenerative events, such that the magnitude of endothelial activation is reflective of the progression of neurodegeneration. Of interest is the differential effect of chemotoxicity and vascular occlusion induced oxidative stress on the pattern of endothelial/angiogenic response and neurodegeneration in the brain.  Purpose: 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. Specifically, we sought to demonstrate the endothelial activation and angiogenic response and how it determines the magnitude of degeneration (PC and PVZ) or proliferation (PVZ)after the treatment phase, and subsequently, after the withdrawal phase. Methods: 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 10days (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. Result: 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. This was further supported by an increase in cell proliferation (↑Ki-67), neuronal metabolism/proliferation (↑NSE) and neurofilament deposition (↑NF). We also observed that neurosurvival was significant in the vascular occlusion withdrawal group (VO-I) while neurogenic proliferation was significant in cyanide toxicity withdrawal (CN-I). Conclusion: 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.