Development of blood vessel-related radiation damage in the fimbria of the central nervous system

Reinhold, H; Calvo, W; Hopewell, J. W.; Berg, A. P. Van Den

doi:10.1016/0360-3016(90)90264-k

Cited by 138 publications

(86 citation statements)

References 12 publications

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“…In the subacute phase, there was vascular dilation (25) and reactive astrogliosis (25,27). Some studies have found that reactive astrogliosis is a predominant histologic change as early as 3 to 24 hours postradiation (28) until 24 weeks postradiation (18). This finding is in agreement with our results, which showed reactive astrogliosis in the earlier phase post radiation (4-24 weeks).…”

Section: Discussionsupporting

confidence: 93%

“…Forty 12-wk-old female SpragueDawley rats (n = 40) with mean body weight 291 F 20 grams were divided into 2 separate batches to receive irradiation of 25 or 30 Gy to the right hemibrains with a single highly collimated (circular field of 12.5 mm diameter) 6MV photon beam from a linear accelerator (Varian) under anesthesia. This radiation dose induces changes in rat brains with a similar latent period as has been described in humans (18) and is the minimum required to produce selective late WM necrosis without deaths or gross neurologic deficits, and is a well-established animal model for the evaluation of late radiation-induced brain injury (15,18). The rats were positioned with the aid of the treatment room lasers, which are well-aligned to within 1-mm accuracy of the isocenter at the right frontoparietal region.…”

Section: Methodsmentioning

confidence: 60%

“…Previous studies using animal models have shown dynamic histopathologic changes with time in radiation-induced WM damage (18,(24)(25)(26)(27). Initial acute changes were characterized as lymphocyte infiltration, reduction of vascular endothelium and oligodendrocyte and their progenitors (24).…”

Section: Discussionmentioning

confidence: 99%

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Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model

et al. 2009

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Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (L // ), and radial diffusivity (L ? ) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in L // from 4 to 40 weeks postradiation, and an increase in L ? with return to baseline in L // at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in L // correlated with reactive astrogliosis (P < 0.01) and L ? correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in L // and L ? . DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 60%

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Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model

et al. 2009

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“…Rubin et al (56) irradiated rat brains with 60 Gy and found BBB disruption and vascular leak at 2 weeks postexposure. Reinhold et al (57) found more diffuse changes in rat brains when using more therapeutically relevant dosages of 20 to 25 Gy, including dilation of the blood vessel lumen, thickening of the blood vessel wall, enlargement of endothelial cell nuclei, and hypertrophy of adjacent astrocytes. Mima et al (58) found that in rat brains exposed to 25 Gy of radiation the Pglycoprotein expression was reduced to 60% of that seen in control animals.…”

Section: Radiation and The Bbbmentioning

confidence: 99%

The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses

Deeken

Löscher

2007

Clinical Cancer Research

626

492

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Despite scientific advances in understanding the causes and treatment of human malignancy, a persistent challenge facing basic and clinical investigators is how to adequately treat primary and metastatic brain tumors.The blood-brain barrier is a physiologic obstruction to the delivery of systemic chemotherapy to the brain parenchyma and central nervous system (CNS). A number of physiologic properties make the endothelium in the CNS distinct from the vasculature found in the periphery. Recent evidence has shown that a critical aspect of this barrier is composed of xenobiotic transporters which extrude substrates from the brain into the cerebrospinal fluid and systemic circulation. These transporters also extrude drugs and toxins if they gain entry into the cytoplasm of brain endothelial cells before they enter the brain. This review highlights the properties of the blood-brain barrier, including the location, function, and relative importance of the drug transporters that maintain this barrier. Primary and metastatic brain malignancy can compromise this barrier, allowing some access of chemotherapy treatment to reach the tumor.The responsiveness of brain tumors to systemic treatment found in past clinical research is discussed, as are possible explanations as to why CNS tumors are nonetheless able to evade therapy. Finally, strategies to overcome this barrier and better deliver chemotherapy into CNS tumors are presented.Despite the dramatic advances in understanding the molecular basis for carcinogenesis and the development of new targeting agents to treat malignancies, a critical challenge that continues to face cancer researchers is overcoming the sanctuary for primary and metastatic disease found within the central nervous system (CNS). Brain metastases occur in a significant percentage of patients with common malignancies, with 5-year cumulative incidence rates of 16% in lung cancer patients, 7% of breast cancer patients, and 5% of patients with colon cancer (1). In diseases such as melanoma, the incidence of brain metastatic disease is reported to be as high as 55% (2). Autopsy studies show that in patients who die from cancer, up to 25% of them develop brain metastases (3).The incidence of brain metastatic disease is on the rise (4). This could be due to a number of factors, including earlier brain screening for CNS disease in cancers known to spread to the brain; improved and more widely available radiological techniques such as magnetic resonance imaging; and improved therapies to treat systemic disease, which are prolonging survival and, in turn, increasing the risk of developing metastases to the brain. The irony is that as our therapies are improving clinical outcomes and prolonging survival, the incidence of CNS disease is on the rise. Furthermore, primary brain malignancies are intrinsically resistant to most chemotherapies for reasons that are poorly understood. These realities demand that we better understand, and learn how to treat, CNS malignancy.This CNS sanctuary for metastatic as well...

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“…Increased risk of ATEs in GBM patients treated with bevacizumab also could be represented by radiation-induced vessels damage. It is known that radiotherapy can induce dilation of the blood vessel lumen, thickening of the blood vessel wall, enlargement of endothelial cell nuclei, and arterial sclerosis [40] that might lead to a predisposition for developing thrombotic events, especially during treatment with bevacizumab.…”

Section: Mechanismsmentioning

confidence: 99%

Practical Management of Bevacizumab-Related Toxicities in Glioblastoma

et al. 2015

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Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect. Because some bevacizumab-related adverse events can be life threatening, it is important to identify risk factors and to establish treatment protocols to minimize treatment-related morbidity and mortality. In glioblastoma patients, the risk of developing certain side effects, such as gastrointestinal perforation, venous thromboembolism, and intracranial hemorrhages, is slightly higher than in patients treated with bevacizumab for other tumor types. We performed a systematic review of the side effects of bevacizumab and their incidence, causal mechanisms, and available treatments. Finally, we identified risk factors and proposed preventive and therapeutic measures for these adverse events. The Oncologist 2015;20:166-175Implications for Practice: Given the widespread use of bevacizumab in clinical practice, it is important to raise clinicians' awareness of the potential risks of this treatment. Our aim was to provide an overview of the most common side effects of bevacizumab and to suggest a practical approach for their management.

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Development of blood vessel-related radiation damage in the fimbria of the central nervous system

Cited by 138 publications

References 12 publications

Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model

Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model

The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses

Practical Management of Bevacizumab-Related Toxicities in Glioblastoma

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