2,5‐Hexanedione Alters Elemental Composition and Water Content of Rat Peripheral Nerve Myelinated Axons

LoPachin, Richard M.; Lehning, Ellen J.; Stack, Edward C.; Hussein, Steven J.; Saubermann, Albert J.

doi:10.1046/j.1471-4159.1994.63062266.x

Cited by 21 publications

(5 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mass fraction of the biomolecules and water in various skin appendages was converted to the volume fraction by using a mass density of 1.35 g/cm 3 [66] and 1 g/cm 3 , respectively (Table 1). The selected values for axoplasm (Squid giant axon) are close to the data reported for small axons (90-91%) [72]. Moreover, since the major portion of Meissner corpuscle's lumen and Remak bundles is occupied by Schwann cells, the water content of Schwann cells (≈75%) [73] was used as a first approximation.…”

Section: ) Watersupporting

confidence: 68%

High-Resolution Model of Human Skin Appendages for Electromagnetic Dosimetry at Millimeter Waves

Haider¹,

Dréan

Sacco³

et al. 2022

IEEE J. Microw.

View full text Add to dashboard Cite

The purpose of this work is to evaluate local power and electric field distributions inside high-resolution 3D anatomical CAD models of cutaneous appendages at 60 GHz upcoming for 5G/6G. The microscale resolution models of cutaneous nerves, lymphatics, pilosebaceous unit, microvasculature, eccrine sweat glands, Meissner corpuscle and Pacinian corpuscle were designed based on morphometric data and microscopic images. The Maxwell's and Hanai's mixture equations were employed to retrieve the complex permittivity of cutaneous appendages based on their free water content. The cutaneous appendages were exposed to a uniform plane wave. The finite element method was used to compute the power loss density (PLD) and internal electric field (E). The results indicate that the maximal PLD in cutaneous appendages occurred for E polarized along their longest dimension. Higher peak PLD was observed in high water content cutaneous appendages such as acrosyringium (45%), epidermal axon (37.9%), Pacinian corpuscle (32.5%), blood capillary (30.6%), lymph capillary (20%) and arrector pili muscle (13.5%) compared to the surrounding skin. Higher E was detected in low water content hair with the peak E 45.1% greater than in surrounding skin. The interfaces of the cutaneous appendages also manifested a boost (23.8%-60.9%) in PLD compared to the surrounding skin. Detailed physical interpretation of observed phenomena is provided in the article. These results provide an insight into microscale power deposition in skin at frequencies upcoming for wireless communications.

show abstract

Section: ) Watersupporting

confidence: 68%

High-Resolution Model of Human Skin Appendages for Electromagnetic Dosimetry at Millimeter Waves

Haider¹,

Dréan

Sacco³

et al. 2022

IEEE J. Microw.

View full text Add to dashboard Cite

show abstract

“…With regard to the potential role of 2,5-HD-induced transganglionic upregulation of nNOS expression in the gracile nucleus, it has been demonstrated that 2,5-HD is an axonal neurotoxin that prevents the normal proximal-to-distal transport of neurofilaments, resulting in the formation of neurofilamentous axonal swellings (Anthony, et al, 1983; LoPachin, et al, 1994; Spencer, et al, 1979). The gracile nucleus receives ascending input from primary afferent fibers of the sciatic nerve, which has the longest axons in the body (Leem, et al, 1994; Ueyama, et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…The neurotoxicity of 2,5-HD in rats were performed by systemic injection plus local administration of the compound to induce intoxication on the sciatic nerve and conducted the same as previously described (Al-Chaer, et al, 1997; LoPachin, et al., 1994). Briefly, animals were treated by a single dose injection of 2,5-HD (400 mg/kg, i.p.)…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies showed that pain and pressure thresholds are decreased in Zucker Diabetic Fatty (ZDF) rats, a type II diabetic model (Rong, Ma, 2011; Russell, et al, 2008; Zhuang, et al, 1997). Several studies demonstrated that systemic administration of 2,5-hexanedione (2,5-HD) causes neurofilamentous axonal swellings and damages, which prevent proximal-to-distal transport of neurofilaments and other substances, resulting in profound neuropathic changes including hyperalgesia and limb paralysis (Anthony, et al, 1983; LoPachin, et al, 1994). However, the neural pathways and neurotransmissions responsible for the increased susceptibility of the sensory neurons to non-noxious and noxious stimuli in diabetic and chemical neuropathies are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impaired expression of neuronal nitric oxide synthase in the gracile nucleus is involved in neuropathic changes in Zucker Diabetic Fatty rats with and without 2,5-hexanedione intoxication

Ma¹,

Peterson

Magee³

et al. 2016

Neuroscience Research

View full text Add to dashboard Cite

These studies examined the influence of 2,5-hexanedione (2,5-HD) intoxication on expression of neuronal nitric oxide synthase (nNOS) in the brainstem nuclei in Zucker Diabetic Fatty (ZDF) vs. lean control (LC) rats. Functional neuropathic changes were also investigated following axonal damage and impaired axonal transport induced by the treatment. Animals were intoxicated by i.p. injection of 2,5-HD plus unilateral administration of 2,5-HD over the sciatic nerve. The mechanical thresholds and withdrawal latencies to heat and cold stimuli on the foot were measured at baseline and after intoxication. The medulla sections were examined by nNOS immunohistochemistry and NADPH-diaphorase histochemistry at the end of the treatments. The mechanical thresholds and withdrawal latencies were significantly decreased while nNOS immunostained neurons and NADPH-diaphorase positive cells were selectively reduced in the gracile nucleus at baseline in ZDF vs. LC rats. NADPH-diaphorase reactivity and nNOS positive neurons were increased in the ipsilateral gracile nucleus in LC rats following 2,5-HD intoxication, but its up-regulation was attenuated in ZDF rats. These results suggest that diabetic and chemical intoxication-induced nNOS expression is selectively reduced in the gracile nucleus in ZDF rats. Impaired axonal damage-induced nNOS expression in the gracile nucleus is involved in neuropathic pathophysiology in type II diabetic rats.

show abstract

“…The subsequent neurofilamentous swellings would initiate axon degeneration and characteristic neurological deficits [4, 10]. Other studies however identified axon atrophy as a significant feature of γ-diketone neuropathy [e.g., see 11, 12]. To resolve this apparent conflict, we conducted a series of quantitative morphometric studies to characterize the spatiotemporal expression of axonal swelling, atrophy and degeneration in conventionally fixed central [13, 14] and peripheral [15, 16] nerves of HD-intoxicated rats.…”

Section: γ-Diketone Neuropathy – Morphometric Analysesmentioning

confidence: 99%

Toxic neuropathies: Mechanistic insights based on a chemical perspective

LoPachin

Gavin

2015

Neuroscience Letters

Self Cite

View full text Add to dashboard Cite

2,5-Hexanedione (HD) and acrylamide (ACR) are considered to be prototypical among chemical toxicants that cause central-peripheral axonopathies characterized by distal axon swelling and degeneration. Because the demise of distal regions was assumed to be causally related to the onset of neurotoxicity, substantial effort was devoted to deciphering the respective mechanisms. Continued research, however, revealed that expression of the presumed hallmark morphological features was dependent upon the daily rate of toxicant exposure. Indeed, many studies reported that the corresponding axonopathic changes were late developing effects that occurred independent of behavioral and/or functional neurotoxicity. This suggested that the toxic axonopathy classification might be based on epiphenomena related to dose-rate. Therefore, the goal of this mini-review is to discuss how quantitative morphometric analyses and the establishment of dose-dependent relationships helped distinguish primary, mechanistically relevant toxicant effects from non-specific consequences. Perhaps more importantly, we will discuss how knowledge of neurotoxicant chemical nature can guide molecular-level research toward a better, more rational understanding of mechanism. Our discussion will focus on HD, the neurotoxic γ-diketone metabolite of the industrial solvents n-hexane and methyl-n-butyl ketone. Early investigations suggested that HD caused giant neurofilamentous axonal swellings and eventual degeneration in CNS and PNS. However, as our review will point out, this interpretation underwent several iterations as the understanding of γ-diketone chemistry improved and more quantitative experimental approaches were implemented. The chemical concepts and design strategies discussed in this mini-review are broadly applicable to the mechanistic studies of other chemicals (e.g., n-propyl bromine, methyl methacrylate) that cause toxic neuropathies.

show abstract

2,5‐Hexanedione Alters Elemental Composition and Water Content of Rat Peripheral Nerve Myelinated Axons

Cited by 21 publications

References 32 publications

High-Resolution Model of Human Skin Appendages for Electromagnetic Dosimetry at Millimeter Waves

High-Resolution Model of Human Skin Appendages for Electromagnetic Dosimetry at Millimeter Waves

Impaired expression of neuronal nitric oxide synthase in the gracile nucleus is involved in neuropathic changes in Zucker Diabetic Fatty rats with and without 2,5-hexanedione intoxication

Toxic neuropathies: Mechanistic insights based on a chemical perspective

Contact Info

Product

Resources

About