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

Michael OO, Gbolahan BW, Ansa CE, Abdulbasitand A, Azeez IO - Ann Neurosci (2015)

Bottom Line: 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.The increase in CD45 expression coupled with a reduced CD31/GFAP after the withdrawal phase was evident of vascular remodeling and neurosurvival.Generally, we found that degeneration was prominent in the parietal cortex and less in the periventricular zone for both forms of ischemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, College of Medicine and Health Sciences, AfeBabalola University, Ekiti State Ado-Ekiti, Nigeria.

ABSTRACT

Background: 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.

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.

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 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*.

Results: 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.

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.

No MeSH data available.


Related in: MedlinePlus

Coronal section of the brain showing a branch of the MCA close to the third ventricle (A) Microscopic anatomy of the artery demonstrated in haematoxylin and eosin staining (Magnification X100) to show the lumen and tunica media/intima in cyanide toxicity and vascular occlusion; after the treatment and withdrawal phases. An increase in the tunica media/intima thickness was observed in VO and was accompanied by a decrease in lumen width. In cyanide toxicity, degenerative changes were observed in the tunica media/intima; consequently, a decrease in wall thickness and lumen width was recorded in this group. A common set of event in the CN and VO is the decrease in lumen width and an increase in vascular resistance shown by the lumen width/wall thickness ratio (Figure 1D). After the withdrawal phase, regenerative changes such as increased lumen width, reduced vascular resistance and increased cell count were seen in the CN-I and VO-I. Degenerative changes were more pronounced in cyanide toxicity after the treatment phase with a LTR value of 2.44. Sequel After to the withdrawal of cyanide treatment in CN-I, the LTR value increased to 3.67 after the withdrawal phase, thus, a decreased vascular resistance (Figure 1D). Similarly, after vascular occlusion, vascular resistance increased in the artery (3.11) when compared with the control (4.55) and decreased after the withdrawal phase (VO-I; 4.00). This further supports the change in lumen width observed in histology after the treatment (↓lumen width and ↓LTR) and the improvement seen after the withdrawal phase (↑lumen width and ↑LTR). (B) CD31 immunohistochemistry to demonstrate endothelial adhesion molecule PECAM-1 during endothelial proliferation in cyanide toxicity and vascular occlusion induced oxidative stress. Endothelial proliferation (↑CD31) was observed in cyanide toxicity (CD31+++) and vascular occlusion (CD31++) after the treatment phase. Similar to our observations in the LTR and histology (Figure 1A and 1D), a reduction in endothelial proliferation (↓wall thickness) was observed after the withdrawal phase. This was highly significant in CN-I (CD31--) and was less significant in VO-I (CD31+) (C) Blood monocytes and phagocytes (CD45) were demonstrated around the artery to determine their role in pro-inflammation (treatment) and remodeling (withdrawal) during oxidative stress. Interestingly, VO (CD45+) and CN (CD45++) showed a significant reduction in monocyte expression when compared with the control (CD45+++) signifying the noninvolvement of these cells in pro-inflammatory response. However, after the withdrawal phase, the expression of CD45/monocytes increased significantly in VO-I (CD45+++) and no significant change was observed in CN-I (CD45+). Subsequent analysis reveals that CD45/monocyte expression was associated with post-ischemia remodeling and not inflammatory response in oxidative stress. Furthermore, the magnitude of vascular remodeling was more significant in vascular occlusion than cyanide toxicity (D) Pie chart representation of the wall thickness, the lumen width and the LTR.
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fig_1: Coronal section of the brain showing a branch of the MCA close to the third ventricle (A) Microscopic anatomy of the artery demonstrated in haematoxylin and eosin staining (Magnification X100) to show the lumen and tunica media/intima in cyanide toxicity and vascular occlusion; after the treatment and withdrawal phases. An increase in the tunica media/intima thickness was observed in VO and was accompanied by a decrease in lumen width. In cyanide toxicity, degenerative changes were observed in the tunica media/intima; consequently, a decrease in wall thickness and lumen width was recorded in this group. A common set of event in the CN and VO is the decrease in lumen width and an increase in vascular resistance shown by the lumen width/wall thickness ratio (Figure 1D). After the withdrawal phase, regenerative changes such as increased lumen width, reduced vascular resistance and increased cell count were seen in the CN-I and VO-I. Degenerative changes were more pronounced in cyanide toxicity after the treatment phase with a LTR value of 2.44. Sequel After to the withdrawal of cyanide treatment in CN-I, the LTR value increased to 3.67 after the withdrawal phase, thus, a decreased vascular resistance (Figure 1D). Similarly, after vascular occlusion, vascular resistance increased in the artery (3.11) when compared with the control (4.55) and decreased after the withdrawal phase (VO-I; 4.00). This further supports the change in lumen width observed in histology after the treatment (↓lumen width and ↓LTR) and the improvement seen after the withdrawal phase (↑lumen width and ↑LTR). (B) CD31 immunohistochemistry to demonstrate endothelial adhesion molecule PECAM-1 during endothelial proliferation in cyanide toxicity and vascular occlusion induced oxidative stress. Endothelial proliferation (↑CD31) was observed in cyanide toxicity (CD31+++) and vascular occlusion (CD31++) after the treatment phase. Similar to our observations in the LTR and histology (Figure 1A and 1D), a reduction in endothelial proliferation (↓wall thickness) was observed after the withdrawal phase. This was highly significant in CN-I (CD31--) and was less significant in VO-I (CD31+) (C) Blood monocytes and phagocytes (CD45) were demonstrated around the artery to determine their role in pro-inflammation (treatment) and remodeling (withdrawal) during oxidative stress. Interestingly, VO (CD45+) and CN (CD45++) showed a significant reduction in monocyte expression when compared with the control (CD45+++) signifying the noninvolvement of these cells in pro-inflammatory response. However, after the withdrawal phase, the expression of CD45/monocytes increased significantly in VO-I (CD45+++) and no significant change was observed in CN-I (CD45+). Subsequent analysis reveals that CD45/monocyte expression was associated with post-ischemia remodeling and not inflammatory response in oxidative stress. Furthermore, the magnitude of vascular remodeling was more significant in vascular occlusion than cyanide toxicity (D) Pie chart representation of the wall thickness, the lumen width and the LTR.

Mentions: The general morphology of the wall of the arteries was demonstrated in a corona section through the whole brain at approximately 1.3 mm anterior to the bregma. Increase in thickness of the wall of the arteries was characteristic of vascular occlusion (Figure 1-VO; 0.09 cm) and can be attributed in part to the mechanical stress induced by the cuffs for the treatment duration. The artery was also characterized by a narrower lumen (0.0028 cm), when compared with the control (0.036 cm) (Figure 1D). The effect of vascular occlusion in this group can be described anatomically as “induced vascular resistance” in the middle cerebral artery. The structural resistance observed in the global vascular occlusion treatment (VO) reduced after the withdrawal phase (VO-I). In the VO-I, the lumen/wall thickness ratio (LTR) increased significantly to 4.00 from the initial value (3.11) observed in the vascular occlusion treatment (Figure 1-VO-I). The increased LTR in this group corresponds to a reduction in wall thickness (0.008cm) and an increase in lumen width (0.032 cm; Figure 1D).


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

Michael OO, Gbolahan BW, Ansa CE, Abdulbasitand A, Azeez IO - Ann Neurosci (2015)

Coronal section of the brain showing a branch of the MCA close to the third ventricle (A) Microscopic anatomy of the artery demonstrated in haematoxylin and eosin staining (Magnification X100) to show the lumen and tunica media/intima in cyanide toxicity and vascular occlusion; after the treatment and withdrawal phases. An increase in the tunica media/intima thickness was observed in VO and was accompanied by a decrease in lumen width. In cyanide toxicity, degenerative changes were observed in the tunica media/intima; consequently, a decrease in wall thickness and lumen width was recorded in this group. A common set of event in the CN and VO is the decrease in lumen width and an increase in vascular resistance shown by the lumen width/wall thickness ratio (Figure 1D). After the withdrawal phase, regenerative changes such as increased lumen width, reduced vascular resistance and increased cell count were seen in the CN-I and VO-I. Degenerative changes were more pronounced in cyanide toxicity after the treatment phase with a LTR value of 2.44. Sequel After to the withdrawal of cyanide treatment in CN-I, the LTR value increased to 3.67 after the withdrawal phase, thus, a decreased vascular resistance (Figure 1D). Similarly, after vascular occlusion, vascular resistance increased in the artery (3.11) when compared with the control (4.55) and decreased after the withdrawal phase (VO-I; 4.00). This further supports the change in lumen width observed in histology after the treatment (↓lumen width and ↓LTR) and the improvement seen after the withdrawal phase (↑lumen width and ↑LTR). (B) CD31 immunohistochemistry to demonstrate endothelial adhesion molecule PECAM-1 during endothelial proliferation in cyanide toxicity and vascular occlusion induced oxidative stress. Endothelial proliferation (↑CD31) was observed in cyanide toxicity (CD31+++) and vascular occlusion (CD31++) after the treatment phase. Similar to our observations in the LTR and histology (Figure 1A and 1D), a reduction in endothelial proliferation (↓wall thickness) was observed after the withdrawal phase. This was highly significant in CN-I (CD31--) and was less significant in VO-I (CD31+) (C) Blood monocytes and phagocytes (CD45) were demonstrated around the artery to determine their role in pro-inflammation (treatment) and remodeling (withdrawal) during oxidative stress. Interestingly, VO (CD45+) and CN (CD45++) showed a significant reduction in monocyte expression when compared with the control (CD45+++) signifying the noninvolvement of these cells in pro-inflammatory response. However, after the withdrawal phase, the expression of CD45/monocytes increased significantly in VO-I (CD45+++) and no significant change was observed in CN-I (CD45+). Subsequent analysis reveals that CD45/monocyte expression was associated with post-ischemia remodeling and not inflammatory response in oxidative stress. Furthermore, the magnitude of vascular remodeling was more significant in vascular occlusion than cyanide toxicity (D) Pie chart representation of the wall thickness, the lumen width and the LTR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4481556&req=5

fig_1: Coronal section of the brain showing a branch of the MCA close to the third ventricle (A) Microscopic anatomy of the artery demonstrated in haematoxylin and eosin staining (Magnification X100) to show the lumen and tunica media/intima in cyanide toxicity and vascular occlusion; after the treatment and withdrawal phases. An increase in the tunica media/intima thickness was observed in VO and was accompanied by a decrease in lumen width. In cyanide toxicity, degenerative changes were observed in the tunica media/intima; consequently, a decrease in wall thickness and lumen width was recorded in this group. A common set of event in the CN and VO is the decrease in lumen width and an increase in vascular resistance shown by the lumen width/wall thickness ratio (Figure 1D). After the withdrawal phase, regenerative changes such as increased lumen width, reduced vascular resistance and increased cell count were seen in the CN-I and VO-I. Degenerative changes were more pronounced in cyanide toxicity after the treatment phase with a LTR value of 2.44. Sequel After to the withdrawal of cyanide treatment in CN-I, the LTR value increased to 3.67 after the withdrawal phase, thus, a decreased vascular resistance (Figure 1D). Similarly, after vascular occlusion, vascular resistance increased in the artery (3.11) when compared with the control (4.55) and decreased after the withdrawal phase (VO-I; 4.00). This further supports the change in lumen width observed in histology after the treatment (↓lumen width and ↓LTR) and the improvement seen after the withdrawal phase (↑lumen width and ↑LTR). (B) CD31 immunohistochemistry to demonstrate endothelial adhesion molecule PECAM-1 during endothelial proliferation in cyanide toxicity and vascular occlusion induced oxidative stress. Endothelial proliferation (↑CD31) was observed in cyanide toxicity (CD31+++) and vascular occlusion (CD31++) after the treatment phase. Similar to our observations in the LTR and histology (Figure 1A and 1D), a reduction in endothelial proliferation (↓wall thickness) was observed after the withdrawal phase. This was highly significant in CN-I (CD31--) and was less significant in VO-I (CD31+) (C) Blood monocytes and phagocytes (CD45) were demonstrated around the artery to determine their role in pro-inflammation (treatment) and remodeling (withdrawal) during oxidative stress. Interestingly, VO (CD45+) and CN (CD45++) showed a significant reduction in monocyte expression when compared with the control (CD45+++) signifying the noninvolvement of these cells in pro-inflammatory response. However, after the withdrawal phase, the expression of CD45/monocytes increased significantly in VO-I (CD45+++) and no significant change was observed in CN-I (CD45+). Subsequent analysis reveals that CD45/monocyte expression was associated with post-ischemia remodeling and not inflammatory response in oxidative stress. Furthermore, the magnitude of vascular remodeling was more significant in vascular occlusion than cyanide toxicity (D) Pie chart representation of the wall thickness, the lumen width and the LTR.
Mentions: The general morphology of the wall of the arteries was demonstrated in a corona section through the whole brain at approximately 1.3 mm anterior to the bregma. Increase in thickness of the wall of the arteries was characteristic of vascular occlusion (Figure 1-VO; 0.09 cm) and can be attributed in part to the mechanical stress induced by the cuffs for the treatment duration. The artery was also characterized by a narrower lumen (0.0028 cm), when compared with the control (0.036 cm) (Figure 1D). The effect of vascular occlusion in this group can be described anatomically as “induced vascular resistance” in the middle cerebral artery. The structural resistance observed in the global vascular occlusion treatment (VO) reduced after the withdrawal phase (VO-I). In the VO-I, the lumen/wall thickness ratio (LTR) increased significantly to 4.00 from the initial value (3.11) observed in the vascular occlusion treatment (Figure 1-VO-I). The increased LTR in this group corresponds to a reduction in wall thickness (0.008cm) and an increase in lumen width (0.032 cm; Figure 1D).

Bottom Line: 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.The increase in CD45 expression coupled with a reduced CD31/GFAP after the withdrawal phase was evident of vascular remodeling and neurosurvival.Generally, we found that degeneration was prominent in the parietal cortex and less in the periventricular zone for both forms of ischemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, College of Medicine and Health Sciences, AfeBabalola University, Ekiti State Ado-Ekiti, Nigeria.

ABSTRACT

Background: 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.

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.

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 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*.

Results: 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.

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.

No MeSH data available.


Related in: MedlinePlus