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Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: implications for chemical-induced peripheral sensory neuropathies.

Jimenez-Andrade JM, Herrera MB, Ghilardi JR, Vardanyan M, Melemedjian OK, Mantyh PW - Mol Pain (2008)

Bottom Line: This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG.Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy.Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA. jmjimene@email.arizona.edu

ABSTRACT
Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG), which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

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CD31+ blood vessel density is significantly higher in cell body-rich areas (CBRA) as compared to nerve fiber-rich areas (NFRA) of the L4 dorsal root ganglia (DRG) and distal and proximal sciatic nerve of the C3H mouse. Regional differences in blood vessel density were determined by quantifying the CD31+ blood vessels/mm2 in 15 μm cut sections of the L4 DRG and attached nerve roots. Each bar of the histograms represents the mean +/- SEM of at least 4 mice and * indicates a difference of p < 0.05 vs CBRA of the L4 DRG.
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Figure 3: CD31+ blood vessel density is significantly higher in cell body-rich areas (CBRA) as compared to nerve fiber-rich areas (NFRA) of the L4 dorsal root ganglia (DRG) and distal and proximal sciatic nerve of the C3H mouse. Regional differences in blood vessel density were determined by quantifying the CD31+ blood vessels/mm2 in 15 μm cut sections of the L4 DRG and attached nerve roots. Each bar of the histograms represents the mean +/- SEM of at least 4 mice and * indicates a difference of p < 0.05 vs CBRA of the L4 DRG.

Mentions: To determine these regional differences in the density of CD31+ blood vessels within L4 DRG, we quantified the CD31+ blood vessels in CBRA and NFRA (Fig 3). The density of CD31+ blood vessels in CBRA (351 ± 27 CD31+ blood vessels/mm2) was significantly higher than that in NFRA (53 ± 8 CD31+ blood vessels/mm2). In order to compare the CD31+ blood vessel density of the CBRA to the peripheral nerves, we quantified CD31+ blood vessel density in two regions of the sciatic nerve. CD31+ blood vessels were observed mainly to run longitudinally along the endoneurium of the sciatic nerve (data not shown). No significant differences in the CD31+ blood vessel density were found between distal (47 ± 2 CD31+ blood vessels/mm2) and proximal (42 ± 6 CD31+ blood vessels/mm2) regions of the sciatic nerve (Fig 3). While the CD31+ blood vessel density in the sciatic nerve was similar in magnitude compared to that in NFRA, it was significantly lower as compared to that in CBRA (Fig 3). Finally, we quantified the CD31+ blood vessel density in the dorsal horn of the spinal cord, as this tissue is highly vascularized [30,31]. Results show that dorsal spinal cord is significantly higher than CBRA and has the highest blood vessel density (555 ± 17 CD31+ blood vessels/mm2) of the tissues evaluated in this study (Fig 3).


Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: implications for chemical-induced peripheral sensory neuropathies.

Jimenez-Andrade JM, Herrera MB, Ghilardi JR, Vardanyan M, Melemedjian OK, Mantyh PW - Mol Pain (2008)

CD31+ blood vessel density is significantly higher in cell body-rich areas (CBRA) as compared to nerve fiber-rich areas (NFRA) of the L4 dorsal root ganglia (DRG) and distal and proximal sciatic nerve of the C3H mouse. Regional differences in blood vessel density were determined by quantifying the CD31+ blood vessels/mm2 in 15 μm cut sections of the L4 DRG and attached nerve roots. Each bar of the histograms represents the mean +/- SEM of at least 4 mice and * indicates a difference of p < 0.05 vs CBRA of the L4 DRG.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2289805&req=5

Figure 3: CD31+ blood vessel density is significantly higher in cell body-rich areas (CBRA) as compared to nerve fiber-rich areas (NFRA) of the L4 dorsal root ganglia (DRG) and distal and proximal sciatic nerve of the C3H mouse. Regional differences in blood vessel density were determined by quantifying the CD31+ blood vessels/mm2 in 15 μm cut sections of the L4 DRG and attached nerve roots. Each bar of the histograms represents the mean +/- SEM of at least 4 mice and * indicates a difference of p < 0.05 vs CBRA of the L4 DRG.
Mentions: To determine these regional differences in the density of CD31+ blood vessels within L4 DRG, we quantified the CD31+ blood vessels in CBRA and NFRA (Fig 3). The density of CD31+ blood vessels in CBRA (351 ± 27 CD31+ blood vessels/mm2) was significantly higher than that in NFRA (53 ± 8 CD31+ blood vessels/mm2). In order to compare the CD31+ blood vessel density of the CBRA to the peripheral nerves, we quantified CD31+ blood vessel density in two regions of the sciatic nerve. CD31+ blood vessels were observed mainly to run longitudinally along the endoneurium of the sciatic nerve (data not shown). No significant differences in the CD31+ blood vessel density were found between distal (47 ± 2 CD31+ blood vessels/mm2) and proximal (42 ± 6 CD31+ blood vessels/mm2) regions of the sciatic nerve (Fig 3). While the CD31+ blood vessel density in the sciatic nerve was similar in magnitude compared to that in NFRA, it was significantly lower as compared to that in CBRA (Fig 3). Finally, we quantified the CD31+ blood vessel density in the dorsal horn of the spinal cord, as this tissue is highly vascularized [30,31]. Results show that dorsal spinal cord is significantly higher than CBRA and has the highest blood vessel density (555 ± 17 CD31+ blood vessels/mm2) of the tissues evaluated in this study (Fig 3).

Bottom Line: This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG.Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy.Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA. jmjimene@email.arizona.edu

ABSTRACT
Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG), which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

Show MeSH
Related in: MedlinePlus