Light and electron microscopic observations on the cerebellum of guinea pigs following low-dose methotrexate

el-Badawi, M G; Fatani, J A; Bahakim, Hassan M.; Abdalla, M. A.

doi:10.1016/0014-4800(90)90045-f

Cited by 12 publications

(6 citation statements)

References 24 publications

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“…MTX-induced neurotoxicity was previously demonstrated in various dosages to rats (El Badawi et al, 1990;Gilbert et al, 1989). In our study, we injected a single ip dose of 20 mg/kg MTX as previously described to cause MTX tissue damage (Uzar et al, 2006;Johovic et al, 2003).…”

Section: Discussionmentioning

confidence: 92%

Beneficial effects of chlorogenic acid on methotrexate-induced cerebellar Purkinje cell damage in rats

Vardı

Parlakpınar

Ateş

2012

Journal of Chemical Neuroanatomy

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Section: Discussionmentioning

confidence: 92%

Beneficial effects of chlorogenic acid on methotrexate-induced cerebellar Purkinje cell damage in rats

Vardı

Parlakpınar

Ateş

2012

Journal of Chemical Neuroanatomy

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“…There was considerable damage to the ependymal lining of the ventricle. Methotrexate-induced astrocytosis, fibrinoid degeneration, and thrombosis of blood vessels were also reported by Badawi et al (1990). Alzheimer type-II astrocytosis was observed in rat brain after intraventricular administration of methotrexate (Gregorios et al 1989).…”

Section: Figmentioning

confidence: 89%

Hippocampal brain amines in methotrexate-induced learning and memory deficit

Madhyastha¹,

Somayaji²,

Rao³

et al. 2002

Can. J. Physiol. Pharmacol.

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Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy, and cognitive dysfunction after long-term treatment. To investigate the cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Its effect on behaviour was tested in the two-compartment conditioned avoidance task and dark-bright arena test. Levels of brain amines in the hippocampal region of the brain were estimated by HPLC. The qualitative and quantitative histopathological changes in the different regions of the hippocampus were studied by cresyl violet staining. Multiple injections (1 or 2 mg/kg) produced convulsions and learning and memory impairment but did not induce anxiolytic activity. They also reduced concentrations of all three brain amines (norepinephrine, dopamine, and serotonin) and the serotonin metabolite 5-hydroxyindoleacetic acid. The CA4 region of the hippocampus was severely affected by intraventricular methotrexate. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy, and that disruption may in turn involve cytotoxic effects of methotrexate on brain tissue. The outcomes of this study may have therapeutic implications in the management of cancer conditions, particularly in childhood lymphoblastic leukemia.

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“…35–38 In the central nervous system, toxicity of methotrexate has been studied and described in the cerebellum of guinea pigs. 39…”

Section: Discussionmentioning

confidence: 99%

Anticancer agents are potent neurotoxins in vitro and in vivo

Rzeski

Pruskil

Macke

et al. 2004

Annals of Neurology

111

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Neurotoxicity of anticancer agents complicates treatment of children with cancer. We investigated neurotoxic effects of common cytotoxic drugs in neuronal cultures and in the developing rat brain. When neurons were exposed to cisplatin (5-100 microM), cyclophosphamide (5-100 microM), methotrexate (5-100 microM), vinblastin (0.1-1 microM), or thiotepa (5-100 microM), a concentration-dependent neurotoxic effect was observed. Neurotoxicity was potentiated by nontoxic glutamate concentrations. The N-methyl-D-aspartate receptor antagonist MK 801 (10 microM), the AMPA receptor antagonists GYKI 52466 (10 microM) and NBQX (10 microM), and the pancaspase inhibitor Ac-DEVD-CHO (1 nM) ameliorated neurotoxicity of cytotoxic drugs. To investigate neurotoxicity in vivo, we administered to 7-day-old rats the following: cisplatin (5-15 mg/kg i.p.), cyclophosphamide (200-600 mg/kg i.p.), thiotepa (15-45 mg/kg), or ifosfamide (100-500 mg/kg) and their brains were analyzed at 4 to 24 hours. Cytotoxic drugs produced widespread lesions within cortex, thalamus, hippocampal dentate gyrus, and caudate nucleus in a dose-dependent fashion. Early histological analysis demonstrated dendritic swelling and relative preservation of axonal terminals, which are morphological features indicating excitotoxicity. After longer survival periods, degenerating neurons displayed morphological features consistent with active cell death. These results demonstrate that anticancer drugs are potent neurotoxins in vitro and in vivo; they activate excitotoxic mechanisms but also trigger active neuronal death.

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Light and electron microscopic observations on the cerebellum of guinea pigs following low-dose methotrexate

Cited by 12 publications

References 24 publications

Beneficial effects of chlorogenic acid on methotrexate-induced cerebellar Purkinje cell damage in rats

Beneficial effects of chlorogenic acid on methotrexate-induced cerebellar Purkinje cell damage in rats

Hippocampal brain amines in methotrexate-induced learning and memory deficit

Anticancer agents are potent neurotoxins in vitro and in vivo

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