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Alterations in the expression of vascular endothelial growth factor in the rat brain following gamma knife surgery.

Cheng L, Ma L, Ren H, Zhao H, Pang Y, Wang Y, Wei M - Mol Med Rep (2014)

Bottom Line: These findings were confirmed by RT‑PCR.A mild decrease in vessel density was observed 4 weeks after GKS, followed by an increase in vessel density between 8 and 20 weeks later.To the best of our knowledge, these data demonstrated for the first time dynamic changes in VEGF expression following GKS and also suggest the importance of VEGF expression in pathological angiogenesis and edema formation following GKS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China.

ABSTRACT
Gamma knife surgery (GKS) is used for the treatment of various brain diseases. However, the mechanisms underlying brain injury following irradiation remain to be elucidated. Given that vascular endothelial growth factor (VEGF) is closely associated with pathological angiogenesis and the permeability of the blood brain barrier (BBB), the present study was designed to analyze temporal alterations in VEGF expression in the cerebral cortex and the effect of VEGF on cerebral edema in rats following GKS. Adult male Wistar rats were subjected to GKS at maximum doses of 60 Gy. Animals were sacrificed between 4 and 24 weeks after GKS. Immunohistochemistry, enzyme‑linked immunosorbent assay and reverse transcription‑polymerase chain reaction (RT‑PCR) were employed for detecting VEGF expression. The vessel density was measured by CD31+ cell count and vascular structures were examined using electron microscopy. Brain water content and BBB permeability were measured in the present study. VEGF expression in the irradiated cortex progressively increased until 16 weeks after GKS when the maximal expression was reached, and then gradually decreased to the control level 24 weeks after GKS. These findings were confirmed by RT‑PCR. A mild decrease in vessel density was observed 4 weeks after GKS, followed by an increase in vessel density between 8 and 20 weeks later. Furthermore, previous studies also demonstrated vascular damage, opening of the BBB and an increase in brain water content occurring simultaneously. To the best of our knowledge, these data demonstrated for the first time dynamic changes in VEGF expression following GKS and also suggest the importance of VEGF expression in pathological angiogenesis and edema formation following GKS.

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Related in: MedlinePlus

Ultrastructural observations of brain capillary endothelial cells. The most pronounced alterations were observed in disturbed vessels and perivascular structures in the irradiated tissue at week 16, which contained enlargement of endothelial nuclei, pykno-chromatin (short arrow), thickening of the capillary basement membrane, folding of the plasma membrane (short arrow) and astroglial edema (long arrow). A, astrocyte; EC, endothelial cells; N, nuclei, L, capillary lumen; BM, basement membrane. Magnification: Left, ×10,000; right, ×50,000.
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f6-mmr-10-05-2263: Ultrastructural observations of brain capillary endothelial cells. The most pronounced alterations were observed in disturbed vessels and perivascular structures in the irradiated tissue at week 16, which contained enlargement of endothelial nuclei, pykno-chromatin (short arrow), thickening of the capillary basement membrane, folding of the plasma membrane (short arrow) and astroglial edema (long arrow). A, astrocyte; EC, endothelial cells; N, nuclei, L, capillary lumen; BM, basement membrane. Magnification: Left, ×10,000; right, ×50,000.

Mentions: Ultrastructural changes of Gamma-irradiated hemispheres of rat brains were detected by transmission electron microscopy. The abnormal brain endothelial cells and surrounding tissue were demonstrated in the irradiated cortex 16 weeks post radiation (Fig. 6). Chromatin condensation and aggregation were observed at the periphery of the nucleons. The membranous structures demonstrated destructive changes, including the thickened basement and the folding of the plasma membrane. The swelling of astrocytic perivascular processes were also observed around damaged endothelial cells. The perivascular cells showed the presence of vacuolar-disturbed structures in the matrix.


Alterations in the expression of vascular endothelial growth factor in the rat brain following gamma knife surgery.

Cheng L, Ma L, Ren H, Zhao H, Pang Y, Wang Y, Wei M - Mol Med Rep (2014)

Ultrastructural observations of brain capillary endothelial cells. The most pronounced alterations were observed in disturbed vessels and perivascular structures in the irradiated tissue at week 16, which contained enlargement of endothelial nuclei, pykno-chromatin (short arrow), thickening of the capillary basement membrane, folding of the plasma membrane (short arrow) and astroglial edema (long arrow). A, astrocyte; EC, endothelial cells; N, nuclei, L, capillary lumen; BM, basement membrane. Magnification: Left, ×10,000; right, ×50,000.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214336&req=5

f6-mmr-10-05-2263: Ultrastructural observations of brain capillary endothelial cells. The most pronounced alterations were observed in disturbed vessels and perivascular structures in the irradiated tissue at week 16, which contained enlargement of endothelial nuclei, pykno-chromatin (short arrow), thickening of the capillary basement membrane, folding of the plasma membrane (short arrow) and astroglial edema (long arrow). A, astrocyte; EC, endothelial cells; N, nuclei, L, capillary lumen; BM, basement membrane. Magnification: Left, ×10,000; right, ×50,000.
Mentions: Ultrastructural changes of Gamma-irradiated hemispheres of rat brains were detected by transmission electron microscopy. The abnormal brain endothelial cells and surrounding tissue were demonstrated in the irradiated cortex 16 weeks post radiation (Fig. 6). Chromatin condensation and aggregation were observed at the periphery of the nucleons. The membranous structures demonstrated destructive changes, including the thickened basement and the folding of the plasma membrane. The swelling of astrocytic perivascular processes were also observed around damaged endothelial cells. The perivascular cells showed the presence of vacuolar-disturbed structures in the matrix.

Bottom Line: These findings were confirmed by RT‑PCR.A mild decrease in vessel density was observed 4 weeks after GKS, followed by an increase in vessel density between 8 and 20 weeks later.To the best of our knowledge, these data demonstrated for the first time dynamic changes in VEGF expression following GKS and also suggest the importance of VEGF expression in pathological angiogenesis and edema formation following GKS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China.

ABSTRACT
Gamma knife surgery (GKS) is used for the treatment of various brain diseases. However, the mechanisms underlying brain injury following irradiation remain to be elucidated. Given that vascular endothelial growth factor (VEGF) is closely associated with pathological angiogenesis and the permeability of the blood brain barrier (BBB), the present study was designed to analyze temporal alterations in VEGF expression in the cerebral cortex and the effect of VEGF on cerebral edema in rats following GKS. Adult male Wistar rats were subjected to GKS at maximum doses of 60 Gy. Animals were sacrificed between 4 and 24 weeks after GKS. Immunohistochemistry, enzyme‑linked immunosorbent assay and reverse transcription‑polymerase chain reaction (RT‑PCR) were employed for detecting VEGF expression. The vessel density was measured by CD31+ cell count and vascular structures were examined using electron microscopy. Brain water content and BBB permeability were measured in the present study. VEGF expression in the irradiated cortex progressively increased until 16 weeks after GKS when the maximal expression was reached, and then gradually decreased to the control level 24 weeks after GKS. These findings were confirmed by RT‑PCR. A mild decrease in vessel density was observed 4 weeks after GKS, followed by an increase in vessel density between 8 and 20 weeks later. Furthermore, previous studies also demonstrated vascular damage, opening of the BBB and an increase in brain water content occurring simultaneously. To the best of our knowledge, these data demonstrated for the first time dynamic changes in VEGF expression following GKS and also suggest the importance of VEGF expression in pathological angiogenesis and edema formation following GKS.

Show MeSH
Related in: MedlinePlus