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. 2023 Jan 14;24(2):1687.
doi: 10.3390/ijms24021687.

Morpho-Functional Characterisation of the Rat Ventral Caudal Nerve in a Model of Axonal Peripheral Neuropathy

Eleonora Pozzi  1   2 , Laura Monza  1   2 , Elisa Ballarini  1   2 , Mario Bossi  1   2 , Virginia Rodriguez-Menendez  1   2 , Annalisa Canta  1   2 , Alessia Chiorazzi  1   2 , Valentina Alda Carozzi  1   2 , Luca Crippa  1   2 , Paola Marmiroli  1   2 , Guido Cavaletti  1   2 , Paola Alberti  1   2
Affiliations

Morpho-Functional Characterisation of the Rat Ventral Caudal Nerve in a Model of Axonal Peripheral Neuropathy

Eleonora Pozzi et al. Int J Mol Sci. .

Abstract

Peripheral Neuropathies (PN) are common conditions whose treatment is still lacking in most cases. Animal models are crucial, but experimental procedures should be refined in some cases. We performed a detailed characterization of the ventral caudal nerve to contribute to a more effective assessment of axonal damage in future PN studies. PN was induced via weekly systemic injection of a neurotoxic drug (paclitaxel); we compared the control and PN-affected rats, performing serial neurophysiological evaluations of the caudal nerve for its entire length. On the same nerve portions, we performed light microscopy and ultrastructural pathological observations to assess the severity of damage and verify the integrity of the surrounding structures. Neurophysiological and morphological analyses confirmed that a severe axonopathy had ensued in the PN group, with a length-dependent modality, matching morphological observations. The site of neurophysiological recording (e.g., distance from the base of the tail) was critical for achieving useful data. A flexible experimental paradigm should be considered in animal studies investigating axonal PN, particularly if the expected severity is relevant; the mid-portion of the tail might be the most appropriate site: there damage might be remarkable but neither as extreme as at the tip of the tail nor as mild as at the base of the tail.

Keywords: anatomy; caudal nerve; chemotherapy induced peripheral neuropathy; chemotherapy induced peripheral neurotoxicity; electron microscopy; light microscopy; morphology; nerve conduction studies; neuropathy; neurotoxicity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Distribution of NCS parameters at baseline, showing values at each site for the whole studies population. In (A) sensory nerve action potential (SNAP) amplitude data is shown, and in (B) sensory conduction velocity (SCV) data. Recordings were obtained following the montage described in methods section (C0 was obtained at the base of the tail and then the montage was placed distally in the adjacent segment C1, and subsequently recordings were repeated for the whole length of the tail up to the tip).
Figure 2
Figure 2
NCS parameters at baseline, ensuring homogeneity between the 2 groups. In (A) sensory nerve action potential (SNAP) amplitude data is shown, and in (B) sensory conduction velocity (SCV) data. Recordings were obtained following the montage described in Figure 1 (C0 was obtained at the base of the tail, then the montage was placed distally in the adjacent segment C1, and subsequently recordings were repeated for the whole length of the tail up to the tip). CTRL: control group; PN: peripheral neuropathy group.
Figure 3
Figure 3
NCS at the end of treatment. In (A) sensory nerve action potential (SNAP) amplitude data is shown and in (B) sensory conduction velocity (SCV) data. Recordings were obtained following the montage described in Figure 1 (C0 was obtained at the base of the tail, then the montage was placed distally in the adjacent segment C1, and subsequently recordings were repeated for the whole length of the tail up to the tip). CTRL: control group; PN: peripheral neuropathy group. *: p-value < 0.05; **: p-value > 0.01; ***: p-value < 0.001.
Figure 4
Figure 4
Light microscopy of significant sections of the whole tail (haematoxylin and eosin). In the upper panel, representative images from control (CTRL) animals, and in the bottom panel representative images of the peripheral neuropathy (PN) animals are shown. CTRL: control group; PN: peripheral neuropathy group. Scale bars represent 100 µm.
Figure 5
Figure 5
Representative images of ventral caudal nerves specimens (toluidine blue). In the upper panel, representative images of the control (CTRL) animals, and in the bottom panel representative images of the peripheral neuropathy (PN) animals are shown. Scale bar shown in the bottom right quadrangle applies to all images. CTRL: control group; PN: peripheral neuropathy group.
Figure 6
Figure 6
Representative images of length-dependent damage observed in the peripheral neuropathy (PN) group. (A): images at the base of the tail. (B): images at the mid of the tail. (C): images at the tip of the tail. (D): a monocyte leaving the vascular compartments to become a tissue macrophage in one of the distal portions.
Figure 7
Figure 7
Neurophysiological recordings montage of the caudal nerve for its whole length. The image represents the whole tail of the rat. The C0 site (i.e., base of the tails) was the starting point of recordings. In the upper right part of the image the reciprocal position of anode, cathode, active and recording electrodes, and ground electrodes is shown. The measurements were repeated moving the electrodes distally, keeping the interelectrode distances constant.
Figure 8
Figure 8
Harvesting procedure. In (A) tendon, localization is shown. In (B) the exposed ventral caudal nerve, after displacing the third and the fourth tendon, is shown. In (C), a close-up of the isolated nerve is shown.
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