Gamma Knife irradiation–induced histopathological changes in the trigeminal nerves of rhesus monkeys

Laboratory investigation

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Object

The authors' goal was to observe histopathological changes in the trigeminal nerve after Gamma Knife surgery (GKS) in rhesus monkeys, and to investigate the radiobiological mechanism of GKS for primary trigeminal neuralgia. The nerve length–dosage effect of irradiation is also discussed.

Methods

One of 5 rhesus monkeys randomly served as a control, and the other 4 monkeys were randomly administered a target radiation dose of 60, 70, 80, or 100 Gy (a different dose in each animal). The size of the collimator was 4 mm, and the target point was the trigeminal nerve root. In each experimental monkey, one side was exposed to single-target-point irradiation, and the contralateral side was exposed to double-target-point irradiation. After 6 months, the trigeminal nerve root was examined using light microscopy, transmission electron microscopy, and immunohistochemistry.

Results

At each radiation dose, the damage to the nerve tissue by single-target-point irradiation was identical to that caused by double-target-point irradiation. In the trigeminal nerve tissues of the monkeys irradiated with 60 and 70 Gy, there was limited nerve demyelination and degeneration, fragmentation, or loss of axons. In the trigeminal nerve tissue of the monkey irradiated with 80 Gy, the nerve tissue showed a disordered structure. In the trigeminal nerve tissue of the monkey irradiated with 100 Gy, there was severe derangement in the structure of the nerve tissue, and extensive demyelination, fragmentation, and loss of axons.

Conclusions

The target doses of 60 and 70 Gy have very little impact on the structure of the trigeminal nerve. Irradiation at 80 Gy can cause partial degeneration and loss of axons and demyelination. A 100-Gy dose can cause some necrosis of neurons. Comparing the single-target-point with the double-target-point irradiation, the extent of damage to the nerve tissue is identical, and no difference in the nerve length–dosage effect was found.

Abbreviations used in this paper: GKS = Gamma Knife surgery; NF-L = neurofilament L; TEM = transmission electronic microscopy; TN = trigeminal neuralgia.

Article Information

Address correspondence to: Jin-Wei Zhang, M.D., Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China, 150086. email: zhangjinwei1970@163.com.

* Drs. Zhao and Yang contributed equally to this study.

Please include this information when citing this paper: published online February 19, 2010; DOI: 10.3171/2010.1.JNS091116.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Photomicrographs of trigeminal nerve sections prepared with routine H & E staining. A: Section showing the normal structure of the trigeminal nerve tissue. B: In the trigeminal nerve tissue of the monkey irradiated with 80 Gy, histological examination revealed focal and patchy interruptions and vacuolation in some nerve fibers. C: In the trigeminal nerve tissue of the monkey irradiated with 100 Gy, there were interruptions, necrosis, and vacuolation in most nerve fibers, which was accompanied by Schwann cell hyperplasia. H & E, original magnification × 200.

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    Photomicrographs of trigeminal nerve sections prepared with multiacid 2R–brilliant green stain for myelin. A: Control trigeminal nerve in longitudinal section. B: Control trigeminal nerve in cross-section. The structure of the nerve tissue was normal, with an orderly arrangement of the nerve fibers, and the myelin sheaths and axons were normally stained. C: The trigeminal nerve irradiated with 60 Gy. There was limited demyelination, fragmentation, and dissolution of axons. D: The trigeminal nerve irradiated with 80 Gy. There was patchy demyelination, fragmentation, and dissolution of axons in some of the nerve fibers. E: The trigeminal nerve irradiated with 100 Gy. There was extensive demyelination, fragmentation, and dissolution of axons. Necrosis in some parts of the nerve fibers was also observed, with scarce myelin sheaths and axons in the region surrounding the lesions. Multiacid 2R–brilliant green, original magnification × 200.

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    Photomicrographs showing immunohistochemical preparations of trigeminal nerve with NF-L stain. A: Control trigeminal nerve; the neurofilament protein of the nerve fibers was stained light brown, and the nerve fibers exhibited an orderly arrangement. B: The trigeminal nerve irradiated with 60 Gy. There was patchy staining of the nerve fibers, indicating the presence of mild degeneration, fragmentation, and dissolution of axons. C: The trigeminal nerve irradiated with 80 Gy. There were extensive patches of negatively stained nerve fibers, suggesting the degeneration, fragmentation, or dissolution of axons in some fibers. D: The trigeminal nerve irradiated with 100 Gy. There was extensive NF-L–negative staining, indicating degeneration, fragmentation, or dissolution of axons in most nerve fibers. Only scarce nerve fibers remained in the region surrounding the lesions. NF-L, original magnification × 100.

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    Photomicrographs showing TEM studies of trigeminal nerve. A: Control trigeminal nerve; TEM revealed a normal structure of the nerve tissue, including compact lamellar structure of the myelin sheaths, intact axon membranes, regular patterns of neurofilament, and normal mitochondrial structure, Schwann cells, and vascular structures. B: The trigeminal nerve irradiated with 60 Gy. The structure of the myelin sheaths and axons was still intact. However, loose lamellar structure of the myelin sheaths, focal collapse, membrane shrinking, and occasional dissolution of axons were observed. C: The trigeminal nerve irradiated with 80 Gy. The nerve tissue showed a disordered structure, with the myelin sheaths partially collapsed, dissolution of axons, disappearance of neurofilaments, vacuolation in mitochondria, and degranulation in rough endoplasmic reticulum. D: The trigeminal nerve irradiated with 100 Gy. The structural derangement was more noticeable, with diffuse plaques in myelin sheaths and dissolution of axons; however, the myelin sheaths remained. Schwann cells shrank in volume, and there were prominent lipid droplets. Original magnification × 6000 (A and D), × 10000 (B), × 2500 (C).

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