Subacute combined degeneration in the spinal cords of totally gastrectomized rats. Ornithine decarboxylase induction, cobalamin status, and astroglial reaction.

BACKGROUND

The totally gastrectomized (TGX) rat is a new experimental model with which to produce widespread spongy vacuolation in spinal cord (SC) white matter, strongly reminiscent of that observed in subacute combined degeneration (SCD) of human SC.

EXPERIMENTAL DESIGN

We did in long-term experiments combined biochemical and histologic studies on SCs from both TGX-rats and rats fed a cobalamin-deficient (Cbl-D) diet. We also investigated the effects of single in vivo administration of some neurotrophic growth factors on the activity of L-ornithine decarboxylase (ODC) (the key-point in the polyamine biosynthetic pathway) in rat SC.

RESULTS

Biochemically, ODC activity was still induced 3 and 6 months after total gastrectomy (TG), while it did not change significantly even after 9 months of feeding a Cbl-D diet. Both TG and feeding the Cbl-D diet greatly decreased the cobalamin level in both serum and SC, although these decreases occurred more slowly in rats fed a Cbl-D diet. Nerve growth factor did not induce ODC in either Cbl-D myeloneuropathy; epidermal growth factor induced ODC in both Cbl-D myeloneuropathies. Basic fibroblast growth factor induced SC ODC only in TGX-rats. Histologically, spongy vacuolation was still widespread 3 and 6 months after TG, while it was spotty even after 9 months of feeding a Cbl-D diet. There was massively increased staining of astrocytes positive for glial fibrillary acidic protein, mainly in the gray matter, in both Cbl-D myeloneuropathies. Finally, repeated in vivo injections of cobalamin to TGX rats only partially reduced ODC induction, the severity of spongy vacuolation, and the increase in glial fibrillary acidic protein-positive astrocytes.

CONCLUSIONS

These results suggest: (a) ODC induction is a persistent and inherent feature in the TG-induced SCD of rat SC; (b) an increase in glial fibrillary acidic protein positive astrocytes in rat SC is not mandatorily connected with an increase in polyamine biosynthesis; (c) a mere deficiency of Cbl seems to be not the only key-point in the pathogenesis of the ODC induction and of the SCD-like lesions, both brought about in rat SC by TG.