Nuclear pore changes and absence of apoptosis in lumbar dorsal root ganglion neurons of doxorubicin-intoxicated rats.

Doxorubicin (DXR) produces degeneration of neurons in the lumbar dorsal root ganglion (DRG) in rats. Light microscopic studies, which included the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling method, and electron microscopic observation revealed that the moderate nuclear and remarkable cytoplasmic degeneration of DRG neurons of Sprague-Dawley rats after intravenous administration of 8 mg/kg of DXR was cell necrosis, not apoptosis. In some neurons, mostly dark and usually with moderate degrees of nuclear degenerative changes, the nuclear pores were decreased in number and obscure 14 and 20 days after DXR administration. DXR enters presumably the nucleus and is partly removed through the nuclear pores. However, the diameters of nuclear pores were similar in DXR-intoxicated and control rats. The changes in nuclear pores of neurons in DXR intoxication, which to our knowledge has not been previously studied, are considered to be part of the degenerative or necrotic changes of DRG neurons.

[The effect of brain-derived neurotrophic factor on elongation of axons after transection with suture-morphometric evaluation].

Brain-derived neurotrophic factor (BDNF) is considered to play an important role in survival, maintenance, development and repair of the peripheral neuron. In this study, the effect of human recombinant BDNF on sprouting and elongation of axons, the early phase of regeneration of nerve fibers, was morphometrically evaluated 7 days following the sciatic nerve transection and juxtaposition of proximal and distal stumps with suture in Sprague-Dawley rats. In the experimental group (test), 20 mg/kg of BDNF was injected subcutaneously every day for seven days in eight rats, starting 30 minutes after the transection. In the control group (control), phosphate buffered-saline alone was injected in nine rats as in the experimental group. The various morphometric parameters were evaluated in the sciatic nerve of each rat of the control and test, 3 mm distal to the site of the transection on light and electron microscopy of Epon-embedded sections. On both light and electron microscopy only a few myelinated fibers with a very thin myelin sheath were found only in one nerve in each of the control and test. However, significant numbers of unmyelinated axons were found in each nerve of the control and test. There were no statistically significant differences in the total fascicular area per nerve, the numbers of myelinated and unmyelinated axons per mm2 of fascicular area and per nerve, their maximum and median diameters and their size distribution histograms between control and test. In addition, there were no statistically significant differences in the numbers of myelin ovoids per mm2 of the fascicular area and per nerve, their maximum and median diameters and their size distribution histograms between control and test. Therefore, we concluded that there was no definite evidence that BDNF promoted the sprouting and elongation of axons, the early phase of the regeneration of nerve fibers, at least under this experimental conditions.