Therapeutic irradiation and brain injury

Sheline, Glenn E.; Wara, William M.; Smith, Vernon

doi:10.1016/0360-3016(80)90175-3

Cited by 896 publications

(290 citation statements)

References 71 publications

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“…Leukoencephalopathy has been seen in cases of cranial irradiation. 14,15 Indeed, cranial irradiation is the prototypical white matter toxin. It has been shown that the degree of neurotoxicity directly correlates with the total dosage of radiation.…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies

2004

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We have observed an increasing number of autopsies on patients with chemotherapy-related complications. One complication is toxic leukoencephalopathy, which is due to a direct toxic effect of chemotherapeutic agents on the central nervous system white matter. Autopsies of four cases of toxic leukoencephalopathy were performed following standard protocols. The brain and spinal cord were examined routinely, and histological sections were taken for evaluation. We report here three patients with hematologic malignancies and one patient with metastatic carcinoma with chemotherapy-induced leukoencephalopathy. The first was a 56-yearold male treated with multiple chemotherapeutics for multiple myeloma. He presented with confusion and focal seizures with a rapid progression to coma and decerebrate posturing. The second was a 36-year-old male who developed mental status changes, ataxia and dysarthria following treatment for lymphoma. The third was a 16-year-old male who developed a profound peripheral and central neuropathy after chemotherapy treatment for Tcell acute lymphoblastic leukemia. The fourth was a 49-year-old female patient who was treated with multiple chemotherapeutics for Stage II breast carcinoma and subsequently developed visual acuity and field defects. The neuropathologic findings in these cases, although similar, varied in severity and distribution. The white matter was affected by severe myelin pallor, edema, and a prominent macrophage infiltrate in each of the cases. The location and extent of the central nervous system pathology correlated with the type and severity of clinical symptoms. These four cases, with their varied presenting symptoms, clinical courses, and degree of pathology, emphasize the importance of considering toxic leukoencephalopathy as an etiology of acute neurologic deterioration following high-dose chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies

2004

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“…Malignant gliomas are extremely radioresistant and difficult to treat (Laramore et al, 1989;Imperato et al, 1991;Phuphanich et al, 1993). Moreover, damage to surrounding normal tissues is a major dose-limiting factor in the treatment of these tumours (Sheline et al, 1980;Leibel et al, 1989). The use of GLA as a therapeutic adjunct may provide benefit in the treatment of this type of malignant brain tumour with radiation.…”

Section: Discussionmentioning

confidence: 99%

γ-Linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells but not to 'normal' rat astrocytes

Vartak

McCaw²,

Davis³

et al. 1998

Br J Cancer

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Summary This study compares the effect of y-linolenic acid (GLA) and its precursor linoleic acid (LA) on survival of 36B10 malignant rat astrocytoma cells and 'normal' rat astrocytes. GLA was cytotoxic to 36B10 cells but not to astrocytes. By contrast, LA supplementation did not affect the survival of either cell types. There were minor differences in the uptake, distribution and use of radiolabelled GLA and LA by the 36B1 0 cells and astrocytes. GLA and LA supplementation increased the total polyunsaturated fatty acid (PUFA) content of the cells indicating increased oxidative potential. However, elevated levels of 8-isoprostane, an indicator of increased oxidative stress, were only observed in the GLA supplemented 36B10 cells. Addition of the antioxidant trolox to GLA-enriched 36B10 cells blocked the cytotoxic effect. Further, GLA enhanced the radiation sensitivity of the astrocytoma cells but not the astrocytes; trolox blocked the GLA-mediated increase in astrocytoma cell radiosensitivity. LA did not affect the radiation response of either cell type. While cyclo-oxygenase inhibitors did not affect GLA cytotoxicity, they blocked the enhanced radiation response of GLA-supplemented cells. The lipoxygenase inhibitor NDGA did not affect the toxicity produced by GLA. Thus, GLA is toxic to the neoplastic astrocytoma cells but not to normal astrocytes.Keywords: polyunsaturated fatty acids; y-linolenic acid; linoleic acid; astrocytoma; astrocyte; radiation Gamma linolenic acid (GLA, 18:3n6) supplementation has been reported to suppress the growth of tumour cells in vitro (Fujiwara et al, 1986;Sangeetha and Das, 1992;Falconer et al, 1994) and in vivo (Karmali et al, 1985;Abou et al, 1987). Interestingly, in separate studies conducted on normal tissues in vivo, it has been reported that dietary GLA decreases the severity of radiation damage to the skin (Hopewell et al, 1993) and CNS (Hopewell et al, 1994). We have previously shown that GLA supplementation can decrease clonogenic cell survival of malignant rat astrocytoma cells and increase their radiosensitivity (Vartak et al, 1997). To determine the therapeutic potential of this observation, it is important to investigate the effect of GLA on 'normal' rat astrocytes. The purpose of this work was to compare the effects of GLA on the survival of 36B10 astrocytoma cells and astrocytes and their response to radiation. The uptake and use of GLA by astrocytoma cells has also been compared with that by astrocytes.The cytotoxic action of polyunsaturated fatty acids (PUFAs) is thought to be mediated predominantly via lipid peroxidation and free radical generation (Begin et al, 1988;Ells et al, 1996). Several studies also indicate that eicosanoid and leukotriene synthesis play an important role in tumour cell proliferation and metastasis (Earashi et al, 1995; Damtew and Spagnuolo, 1997). Arachidonic acid (AA, 20:4n6) and dihomo-y-linolenic acid (DGLA, 20:3n6) are the substrate for the biosynthesis of prostaglandins of the 2-and 1-series respectively (Crawford, 1983 Bell JG et ...

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“…As compared with other causes, the pathogenesis of the cognitive side effects due to late radiation damage is relatively well known. Demyelination and microvascular injury, leading to necrosis [16,17], inflammation and impaired hippocampal neurogenesis, have been implicated in radiation-induced cognitive impairment [18][19][20]. Although the cognitive effects of chemo therapy are less clear, they might result from comparable mechanisms [21,22].…”

Section: Abstract: Brain Tumor • Cognitive Deficits • Cognitive Rehabmentioning

confidence: 99%

Interventions for cognitive deficits in patients with a brain tumor: an update

Gehring

Aaronson

Taphoorn

et al. 2010

Expert Review of Anticancer Therapy

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Therapeutic irradiation and brain injury

Cited by 896 publications

References 71 publications

Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies

Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies

γ-Linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells but not to 'normal' rat astrocytes

Interventions for cognitive deficits in patients with a brain tumor: an update

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