Immunohistochemical study on blood-brain barrier in congenitally hydrocephalic HTX rat brain

The purpose of the present study is to examine the blood-brain barrier in brain of congenital hydrocephalus HTX rats. We investigated the rat brain from postnatal day 1 to 44 using light and electron microscopy and immunohistochemical methods with monoclonal anti-blood-brain barrier (BBB) antibody. HTX rats developed hydrocephalus at 1-2 days after birth. Most rats succumbed to brain changes within 4-5 weeks. Among 136 HTX rats examined, 45 rats succumbed within 1 week after birth, 29 rats between 1-2 weeks, and 4 rats 27-44 days after birth. Out of 88 hydrocephalic rats 54 showed a marked ventricular dilatation, and 34 showed a mild dilatation. Dilatation of lateral ventricles was mild in the rats at 1-2 days after birth, but 3-14-day-old rats showed moderate or marked dilatation. 15-30 days after birth the rats developed mostly marked dilatation of lateral ventricles and third ventricle. Lateral ventricles and third ventricle showed a symmetric dilatation, but ependymal cell layers were well preserved. Aqueduct exhibited no dilatation in any rat. There were spongy appearances and cystic cavities in the white matter around the lateral ventricles. There were glial fibers and capillaries across the cystic cavities. Cystic lesions were also found in the deep subcortical white matter, consisting of spongy changes with extended extracellular spaces and microcysts in the white matter. Immunohistochemically, the anti-BBB reactivity in the normal control rats was at first weak at 2 weeks after birth and increased with the course of development, prominently 4 weeks after birth. Three- and four-week-old HTX rats with hydrocephalus showed moderate positive anti-BBB reaction in the cerebral cortex, the basal ganglia, and around the aqueduct but only a very weak reaction in the deep subcortical white matter and in the subependymal area of lateral ventricles. Laminin immunoreactivity was not different in the capillaries of hydrocephalic brain as compared with normal brain. Electron microscopically, tight junctions were well formed between endothelial cells of capillaries in the subcortical white matter. Occasionally capillaries with partial defect of basal membrane could be found, where the cytoplasm of endothelial cell was protruding between pericytic cytoplasm. Swelling of astrocytic end-feet were found around the microvessels. The results suggest that at the site of the lesion there is underdevelopment or immaturity of the blood-brain barrier.