Early effects of high-dosed absorbable amoscanate on rat brain

Krinke, G.; Graepel, P.; Krueger, Lisa; Thomann, P.

doi:10.1016/0378-4274(83)90128-5

Cited by 5 publications

(9 citation statements)

References 3 publications

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“…1, 2011 TOXICOLOGY OF VENTRICULAR CSF-BORDERING CELLScurative oral dose is typically 10 to 60 mg/kg (Bueding, Batzinger, and Petterson 1976). Adsorbable amoscanate given to an adult induced a lesion in the ependyma but not in CP by three days after administration of consecutive high oral doses (125 or 500 mg/kg) (Clark, Kiel, and Parhad 1982;Krinke et al 1983). Amoscanate caused necrosis by 28 days to the lateral walls of both telencephalic ventricles; interestingly, the lesion ( Figure 11) was confined to the caudate/putamen surface and generally spared the brain, spinal cord, and peripheral nerves.…”

Section: Injuries To Ependymamentioning

confidence: 99%

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The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain

et al. 2010

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Bordering the ventricular cerebrospinal fluid (CSF) are epithelial cells of choroid plexus (CP), ependyma and circumventricular organs (CVOs) that contain homeostatic transporters for mediating secretion/reabsorption. The distributional pathway (''nexus'') of CP-CSF-ependyma-brain furnishes peptides, hormones, and micronutrients to periventricular regions. In disease/toxicity, this nexus becomes a conduit for infectious and xenobiotic agents. The sleeping sickness trypanosome (a protozoan) disrupts CP and downstream CSF-brain. Piperamide is anti-trypanosomic but distorts CP epithelial ultrastructure by engendering hydropic vacuoles; this reflects phospholipidosis and altered lysosomal metabolism. CP swelling by vacuolation may occlude CSF flow. Toxic drug tools delineate injuries to choroidal compartments: cyclophosphamide (vasculature), methylcellulose (interstitium), and piperazine (epithelium). Structurally perturbed CP allows solutes to penetrate the ventricles. There, CSF-borne pathogens and xenobiotics may permeate the ependyma to harm neurogenic stem cell niches. Amoscanate, an anti-helmintic, potently injures rodent ependyma. Ependymal/brain regions near CP are vulnerable to CSF-borne toxicants; this proximity factor links regional barrier breakdown to nearby periventricular pathology. Diverse diseases (e.g., African sleeping sickness, multiple sclerosis) take early root in choroidal, circumventricular, or perivascular loci. Toxicokinetics informs on pathogen, anti-parasitic agent, and auto-antibody distribution along the CSF nexus. CVOs are susceptible to plasma-borne toxicants/pathogens. Countering the physico-chemical and pathogenic insults to the homeostasis-mediating ventricle-bordering cells sustains brain health and fluid balance.

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Section: Injuries To Ependymamentioning

confidence: 99%

“…Magnification is 5053Â. From Krinke et al (1983). Due to unavoidable circumstances the above figures were not originals but were scanned from reprints.…”

Section: Injuries To Circumventricular Organsmentioning

confidence: 99%

The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain

et al. 2010

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“…The clinical signs were essentially non-specific (reduced exploratory activity, reduced body tone, piloerection, braydypnea, reduced body weight gain) except for an ataxic gait and an increased fearfulness which were attributed to the specific central-nervous action of the substance (Krinke et al 1983). The intensity of the signs increased both time-dependent and dose-dependent.…”

Section: Clinical Signsmentioning

confidence: 94%

Electroretinographic assessment of early retinopathy in rats

et al. 1993

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Amoscanate, a substance which damages photoreceptors, was administered orally to Wistar rats in doses of 10, 40, and 125 mg/kg body weight once daily for 3 or 10 days. At both times electroretinographic, ophthalmological, and histopathological examinations of the retina were carried out to compare the sensitivity of conventional methods and to test electroretinography (ERG) for suitability for use in toxicity studies. Time-dependent and dose-dependent effects were found by electroretinography and light microscopy. However, signs of retinal changes appeared earlier and more distinctly in the electroretinogram. Ophthalmological fundus examination in albino rats yielded no characteristic correlate. In conclusion, electroretinography constitutes a valuable supplement to histopathology and is suitable for use in toxicity studies.

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“…Amoscanate is available in two forms: the first, poorly absorbed from the gastrointestinal tract, is used against hookworm infection (Doshi et al 1977); the second, which is well absorbed, is highly effective against schistosomiasis even when administered as a single oral dose (Striebel 1976). Neuropathologic lesions in the rat brain have only been observed when the absorbable form was repeatedly administered at high dosages ; at least three consecutive daily (oral) doses of 125 mg/ kg or 500 mg/ kg were required to damage the ependymal cell lining, and periventricular necrosis occurred following a 1 0-day treatment (Krinke et al 1983). …”

Section: Biologic Featuresmentioning

confidence: 96%

“…92,93). Occasional reactive astrocytes are formed at the border of the damaged area (Krinke et al 1983). The microgranules, in the areas of periventricular necrosis, are characterized by an amorphous, electron-dense structure occasionally showing a pattern of concentric lines; some of them may contain lamellar structures resembling mitochondria (Clark et al 1982).…”

Section: Ultrastructurementioning

confidence: 98%

Neurotoxic Effects of Amoscanate, Rat

Krinke¹

1988

Nervous System

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Early effects of high-dosed absorbable amoscanate on rat brain

Cited by 5 publications

References 3 publications

The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain

The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain

Electroretinographic assessment of early retinopathy in rats

Neurotoxic Effects of Amoscanate, Rat

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