Changes in Neonatally Induced Cerebral Lesions with Advancing Age

Abstract

By two weeks of age the brains of neonatal kittens given a single intraperitoneal injection (1–8 mgm./kg.) of a lipopolysaccharide W from Escherichia coli 011:B4 (Endo B4) contained several telencephalic abnormalities. Large areas of cystic necrosis were present in the white matter in 46% and diffuse astrogliosis in 88% of the animals. In a few, cystic necrosis was also present in the caudate nucleus or thalamus. The long term sequelae (2-21 months following the insult) of these lesions were sought in litters obtained simultaneously from the same cat colony as were the short term experiments. Each of 13 kittens was given a single IP injection of Endo B4 in saline at either 5 or 8 mgm./kg. on the second day of life. 10 littermates were given saline. Weight loss and wide temperature fluctuation usually followed the Endo B4 injection. Cardiovascular collapse was not detected clinically. Paraventricular or gyral white matter glial scars were present in 8 cats. Local peaking of ventricular wall was often present subjacent to paraventricular glial scars. Diffuse Holzer-positive fibrillary gliosis was present in 12 animals. Two cats had marked paucity of cerebral white matter with dilatation of lateral ventricles without glial scars. In another animal, cranial enlargement accompanied severe ventricular dilatation. The third and fourth ventricles and the aqueduct of Sylvius were of normal size in all animals. Focal lesions were present in the thalamus in 3 and in caudate nucleus in 6. Abnormal patterns of myelin and axons surrounded some of the latter. Brain weights of Endo B4 animals were not significantly less than those of littermates. From these findings we infer that white matter cystic necroses in the two week old kitten may have been partially repaired leaving linear glial scars, that the diffuse astrogliosis persists as a fibrillary gliosis, and that marked paucity of hemispheral white matter may follow one or both of these neonatal lesions.