The cerebra of three profoundly retarded adult males with untreated phenylketonuria (PKU) were systematically studied in terms of developmental morphology and histoanatomy against normal age-matched material, technically comparable in preparation. These studies were made possible by the availability of two extensive reference collections of normative neuroanatomic material, the Yakovlev and the Conel collections. The developmental parameters of myelination, width of the cortical plate, cell packing density, neuronal cell size, development of Nissl granulation, dendritic arborization and synaptic spine populations were studied. Our results indicate that there is a marked curtailment of histoanatomical maturation of the brain in PKU by all developmental parameters studied.

Background and Purpose: There is substantial clinical, pathological, and experimental evidence that hypertension aggravates atherosclerosis of the extracranial vessels. The present study assesses the effects of hypertension on the development of cerebral atherosclerosis in nonhuman primates fed an atherogenic diet.Methods: The extent and severity of cerebral atherosclerosis were evaluated morphologically, morphometrically, and biochemically in atherosclerotic monkeys with and without hypertension. Atherosclerosis was induced by feeding a hypercholesterolemic diet for 12 months; hypertension was produced by surgical coarctation of the thoracic aorta.Results: At autopsy, gross atherosclerotic lesions of the major cerebral arteries were observed in 15 of 16 atherosclerotic monkeys with hypertension compared with 5 of 16 atherosclerotic animals without hypertension. In the hypertensive-atherosclerotic group, 38.5% of the vessels examined showed gross

Ten adult cynomolgus monkeys were studied as a non-human primate model of hypertensive cerebrovascular disease. Seven were made hypertensive by surgical coarctation of the aorta and three served as unoperated controls. After survival periods of 8-30 months, the brains were serially sectioned and surveyed for neuropathological changes. The most conspicuous change was minute areas of microinfarction in the white and gray matter. The lesions were of irregular shape with an average maximum diameter of less than 0.5 mm. They were slightly larger in the gray than in the white matter and appeared to be of different ages. Their area of predilection was the white matter of the forebrain, with smaller numbers in the cerebral cortex and scattered lesions elsewhere in the forebrain, brain stem and cerebellum. These microinfarcts did not correspond to usually described lesions in the human brain in hypertension or in other animal models of hypertensive cerebrovascular disease. We suggest that they represent an early change in the natural history of hypertensive neuropathology.