Pathological Changes in Neurons, Neuroglia, and Blood-Brain Barrier Induced by X-Irradiation of Heads of Monkeys

Abstract

IN COMPARISON with the severe changes seen in many tissues, reports concerning the effects of ionizing radiation on the adult central nervous system have usually indicated a relative radioresistance on the part of the brain.* This observation is supported by experiments suggesting that sensitivity to irradiation depends in part on the rate of synthesis of nucleic acids, the lymphocyte and the maturing neuroblast appearing more radiosensitive than the adult neuron.5 Despite these general statements, reports from both clinical \ s=d\ and experimental sources \ s=dd\ reveal that irradiation can produce extensive neuronal pathology and overt neurological disorders. Of key interest here has been the question of the relative importance of direct and indirect neuronal injury: direct by primary alteration of nerve cells, and indirect from changes secondary to alterations in neuroglia or the blood-brain barrier. In this connection, primary impairment of neurons, of neuroglia, and of the vascular system has each been cited as the principal cause of the neurological abnormalities observed.As evidenced by edema and vascular fragility, nonspecific permeability changes may occur in the central nervous system after irradiation. § The concept of a selective barrier between the blood and the brain in the normal animal has generally been accepted, since it has been shown that certain negatively charged substances cir¬ culating in the blood are uniquely incapable of entering the nerve tissue. This phenomenon can be demonstrated grossly by intravenous or intraperitoneal injection of certain vitally staining acid aniline dyes, such as trypan blue, and has often been described since Ehrlich's experiments at the end of the last century. In the normal animal, trypan blue so injected stains the tissues of every organ except the central nervous system. The dura mater, choroid plexus, and walls of cerebral vessels stain vitally, as do the neural stalk and the area postrema; but the dye normally does not penetrate the central nervous system proper.

Early blood-brain barrier disruption after high-dose single-fraction irradiation in rats

“…Macroscopic observation detected more extravasated serum albumin in the gray matter than in the white matter. The cause of this difference is not clear, but may be related to the larger capillary volume in the gray matter than in the white matter (corpus callosum) [6]. This distribution between gray and white matter differs from the distribution of oedema fluid seen in brain tumours, cerebral ischaemia and cold injury [1,12,21].…”

Eight-Year Survival in a Boy with Cerebellar Tumor

“…Ultrastructurally, endothelial cell changes and proliferation are present [16,17]. Delayed radiation encephalopathy includes parenchymal foci of necrosis, particularly of white matter, or demyelination with rela tive preservation of axons as well as the vasculopathy mentioned above [18][19][20][21][22][23][24], Experimentally, metabolic rates of some brain structures are reduced following moderate doses of x-radiation [25]. Whether or not radi ation leukoencephalopathy is related to vascular abnor malities, a number of reports have appeared suggesting that protection of the microcirculation may be possible [26] .…”

Demyelinization Induced in the Brains of Monkeys by Means of Fast Neutrons

“…The findings do not disclose whether the effects are to be attributed to the physical characteristics of neutrons as opposed to other forms of ionizing radiation, or to one or another of the conditions of exposure, notably the energy, the dose, or the dose rate. Many observations have shown that x-ray and gamma radiation produce areas of necrosis in the grey and white matter of the brain; but these lesions are regularly associated with marked vascular sclerosis, and they have generally been attributed to ischemia (10)(11)(12). A degeneration of the cerebral tissues has been noted, however, in the absence of conspicuous changes in the blood vessels, in animals exposed to 23 mev.…”