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Keywords = Camelford in Cornwall

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11 pages, 6462 KiB  
Case Report
Aluminium in Brain Tissue in Epilepsy: A Case Report from Camelford
by Matthew Mold, Jason Cottle and Christopher Exley
Int. J. Environ. Res. Public Health 2019, 16(12), 2129; https://doi.org/10.3390/ijerph16122129 - 16 Jun 2019
Cited by 20 | Viewed by 14201
Abstract
(1) Introduction: Human exposure to aluminium is a burgeoning problem. In 1988, the population of the Cornish town of Camelford was exposed to exceedingly high levels of aluminium in their potable water supply. Herein we provide evidence that aluminium played a role in [...] Read more.
(1) Introduction: Human exposure to aluminium is a burgeoning problem. In 1988, the population of the Cornish town of Camelford was exposed to exceedingly high levels of aluminium in their potable water supply. Herein we provide evidence that aluminium played a role in the death of a Camelford resident following development of late-onset epilepsy. (2) Case summary: We have measured the aluminium content of brain tissue in this individual and demonstrated significant accumulations of aluminium in the hippocampus (4.35 (2.80) µg/g dry wt.) and the occipital lobe (2.22 (2.23) µg/g dry wt., mean, SD, n = 5), the latter being associated with abnormal calcifications. Aluminium-specific fluorescence microscopy confirmed the presence of aluminium in both of these tissues and made the consistent observation of aluminium-loaded glial cells in close proximity to aluminium-rich cell/neuronal debris. These observations support an inflammatory component in this case of late-onset epilepsy. Congo red failed to identify any amyloid deposits in any tissue while thioflavin S showed extensive extracellular and intracellular tau pathologies. (3) Discussion: We present the first data showing aluminium in brain tissue in epilepsy and suggest, in light of complementary evidence from scientific literature, the first evidence that aluminium played a role in the advent of this case of late-onset adult epilepsy. Full article
(This article belongs to the Section Environmental Health)
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Figure 1

Figure 1
<p>Aluminium-loaded cells in the frontal cortex, morphologically compatible with glia, identified by punctate orange fluorescence, are in close proximity to aluminium-rich extracellular debris (<b>a</b>) Lumogallion staining of the parietal lobe (<b>b</b>) is negative for the presence of aluminium with cortical lipofuscin deposits highlighted via yellow fluorescence. Magnified inserts are denoted by asterisks, including a bright-field overlay in the lower panels. Magnification × 400, scale bars: 50 μm.</p> Full article ">Figure 2
<p>Intracellular aluminium in microglia in close proximity to extracellular deposits of aluminium-rich debris (<b>a</b>) and in astrocyte-like cells (<b>b</b>) in the occipital cortex. Magnified inserts are depicted (asterisks) with the bright field overlay shown in lower panels. Magnification × 400, scale bars: 50 μm.</p> Full article ">Figure 3
<p>Extracellular aluminium highlighted via an intense orange fluorescence emission in the white matter of the temporal lobe (<b>a</b>). Intracellular aluminium was also noted in the temporal cortex (<b>b</b>) as highlighted via punctate orange fluorescence within inflammatory cells in the vessel wall. Magnified inserts and their bright field overlays are denoted by asterisks. Magnification × 400, scale bars: 50 μm.</p> Full article ">Figure 4
<p>Intracellular aluminium in glial-like cells and within surrounding cellular debris in the parahippocampal gyrus (<b>a</b>) and in glial cells exhibiting astrocyte-like processes in the hippocampus (<b>b</b>). Magnified inserts are depicted (asterisks) with the bright field channel overlaid. Magnification × 400, scale bars: 50 μm.</p> Full article ">Figure 5
<p>Congo red stained serial tissue sections of the occipital lobe, revealing multiple spherulites. Spherulites were noted via a Maltese-Cross diffraction pattern (white circles) under fully polarised light (<b>a</b>,<b>c</b>) and an ovoid-like morphology (grey circles) under bright field illumination (<b>b</b>,<b>d</b>). Spherulites were exclusively distributed across the grey-white matter interface of the occipital lobe. Magnification × 200, scale bars: 100 μm.</p> Full article ">Figure 6
<p>Thioflavin S (ThS) staining of the frontal (<b>a</b>,<b>b</b>), parietal (<b>c</b>,<b>d</b>), occipital (<b>e</b>,<b>f</b>) and temporal lobes (<b>g</b>) and hippocampus (<b>h</b>) revealed cortical neurofibrillary tangles (NFTs) as highlighted via a green fluorescence emission. ThS-reactive NFTs were noted in pia mater, as demonstrated in the frontal cortex (<b>a</b>) and hippocampus (<b>h</b>). Ring-like NFTs were also noted in the choroid plexus (<b>h</b>). Magnified inserts are denoted with asterisks. Magnifications: (<b>a</b>–<b>f</b>): × 40, (<b>g</b>): × 1000, (<b>h</b>): × 200, scale bars: (<b>a</b>–<b>f</b>): 50 μm, (<b>g</b>): 20 μm, (<b>h</b>): 100 μm.</p> Full article ">
10 pages, 6046 KiB  
Case Report
Intracellular Aluminium in Inflammatory and Glial Cells in Cerebral Amyloid Angiopathy: A Case Report
by Matthew Mold, Jason Cottle, Andrew King and Christopher Exley
Int. J. Environ. Res. Public Health 2019, 16(8), 1459; https://doi.org/10.3390/ijerph16081459 - 24 Apr 2019
Cited by 18 | Viewed by 12243
Abstract
(1) Introduction: In 2006, we reported on very high levels of aluminium in brain tissue in an unusual case of cerebral amyloid angiopathy (CAA). The individual concerned had been exposed to extremely high levels of aluminium in their potable water due to a [...] Read more.
(1) Introduction: In 2006, we reported on very high levels of aluminium in brain tissue in an unusual case of cerebral amyloid angiopathy (CAA). The individual concerned had been exposed to extremely high levels of aluminium in their potable water due to a notorious pollution incident in Camelford, Cornwall, in the United Kingdom. The recent development of aluminium-specific fluorescence microscopy has now allowed for the location of aluminium in this brain to be identified. (2) Case Summary: We used aluminium-specific fluorescence microscopy in parallel with Congo red staining and polarised light to identify the location of aluminium and amyloid in brain tissue from an individual who had died from a rare and unusual case of CAA. Aluminium was almost exclusively intracellular and predominantly in inflammatory and glial cells including microglia, astrocytes, lymphocytes and cells lining the choroid plexus. Complementary staining with Congo red demonstrated that aluminium and amyloid were not co-located in these tissues. (3) Discussion: The observation of predominantly intracellular aluminium in these tissues was novel and something similar has only previously been observed in cases of autism. The results suggest a strong inflammatory component in this case and support a role for aluminium in this rare and unusual case of CAA. Full article
►▼ Show Figures

Figure 1

Figure 1
<p>Schematic depicting a 5 μm tissue section of the parietal lobe. White matter and grey matter are highlighted yellow and grey, respectively. Lumogallion-reactive aluminium was identified through sequential scanning of a 5 μm tissue section, with positive bright orange fluorescence denoted by red crosses (regions 1–4). On an adjacent serial section, Congo red positive regions showing apple-green birefringence under polarised light identified amyloid and spherulites, denoted by red circles (regions 5 and 6).</p> Full article ">Figure 2
<p>Schematic depicting a 5 μm tissue section of the occipital lobe. White matter and grey matter are highlighted yellow and grey, respectively. Lumogallion-reactive aluminium was identified through sequential scanning of a 5 μm tissue section, with positive bright orange fluorescence denoted by red crosses (regions 1–6). On an adjacent serial section, Congo red positive regions showing apple-green birefringence under polarised light identified amyloid and spherulites, denoted by red circles (regions 7 and 8).</p> Full article ">Figure 3
<p>Schematic depicting a 5 μm tissue section of the temporal lobe. White matter and grey matter are highlighted yellow and grey, respectively. Lumogallion-reactive aluminium was identified through sequential scanning of a 5 μm tissue section with positive bright orange fluorescence denoted by red crosses (regions 1–8). On an adjacent serial section, Congo red positive regions showing apple-green birefringence under polarised light identified amyloid, denoted by red circles (regions 9 and 10).</p> Full article ">Figure 4
<p>Schematic depicting a 5 μm tissue section of the hippocampus. White matter and grey matter are highlighted yellow and grey, respectively. Lumogallion-reactive aluminium was identified through sequential scanning of a 5 μm tissue section, with positive bright orange fluorescence denoted by red crosses (1–8).</p> Full article ">Figure 5
<p>Lumogallion-reactive aluminium in glial cells in white matter of the parietal lobe. Intracellular bright orange fluorescence was noted in glial cells surrounding vasculature (<b>a</b>) and in areas depicting cellular debris (<b>b</b>). Magnified inserts are denoted by asterisks with lower panels including a bright field overlay. Magnification 400×; scale bars 50 μm.</p> Full article ">Figure 6
<p>Intracellular lumogallion-reactive aluminium in glial cells in grey and white matter of the occipital lobe. Cells morphologically compatible with microglia surrounding astrocytes (<b>a</b>) and an aluminium loaded astrocytic-like cell, exhibiting intracellular bright orange fluorescence (<b>b</b>), were identified in grey and white matter regions, respectively. Magnified inserts are denoted by asterisks with lower panels including a bright field overlay. Magnification 400×; scale bars 50 μm.</p> Full article ">Figure 7
<p>Intracellular lumogallion-reactive aluminium identified in grey and white matter regions of the temporal lobe. Glial cells exhibiting astrocytic-like processes displayed bright orange fluorescence in grey (<b>a</b>) and white (<b>b</b>) matter regions. Magnified inserts are denoted by asterisks with lower panels including a bright field overlay. Magnification 400×; scale bars 50 μm.</p> Full article ">Figure 8
<p>Intracellular lumogallion-reactive aluminium localised within the hippocampus. Intracellular bright orange fluorescence was noted in inflammatory cells in the vessel wall (<b>a</b>) and within ependymal cells lining the choroid plexus (<b>b</b>). Magnified inserts are denoted by asterisks with lower panels including a bright field overlay. Magnification 400×; scale bars 50 μm.</p> Full article ">Figure 9
<p>Congo red reactive amyloid deposited independently of lumogallion-reactive aluminium in the temporal lobe. Positive Congo red staining was observed under bright field (<b>a</b>), partial (<b>b</b>) and fully (<b>c</b>) polarised light, demonstrating an apple-green birefringence confirming the presence of amyloid with a β-pleated sheet conformation. Intracellular aluminium identified in glial-like cells (<b>d</b>) was not co-located with amyloid within the vasculature. Magnified inserts are denoted by asterisks. Magnification 100×; scale bars 200 μm.</p> Full article ">
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