The uptake of DH-ergotoxine by different parts of the cat brain.

The distribution pattern of 3H-DH-ergotoxine, labelled by a direct hydration with tritium, was investigated in the cat brain. Apart from the pituitary gland, the brain shows an average DH-ergotoxine concentration of 10(-7) M. A 15% greater incorporation of DH-ergotoxine occurs in the cerebellum than in the cerebrum. In gradient centrifugation studies it is seen that 60% of the incorporated DH-ergotoxine is localized in the synaptosomal fraction. This finding seems to verify the microhistautoradiographic results of this investigation. The observation of a DH-ergotoxine binding in selected structures of the CNS , predominantly the synapses, could explain central nervous activities of DH-ergotoxine.

The effect of "ouabain" on the ultrastructure of cerebral arterioles and surrounding tissue, studied by a cannulation of a cerebral artery.

A technique for cannulation of a parietal branch of the middle cerebral artery is described by which high but local concentrations of substances can be achieved in cortical vessels. Using this technique it was shown that ouabain, a specific inhibitor of the Na+-K+-ATPase enzyme system, can produce alterations in the blood brain barrier (BBB) permeability as seen by the passage of Evans Blue into cortical tissue. Electron microscopy revealed changes in the endothelium of cerebral arterioles ranging from an increase in the number of vesicles and vacuoles to complete breakdown of cytoplasm and membranes. Swelling of the peri-arteriolar end feet of protoplasmic astroglia and of dendrites was characteristic of tissue surrounding affected arterioles. Swollen fibrous astrocytes, oligodendrocytes and microglia were not seen even in areas of vasogenic edema. These results are discussed in terms of current ideas of the BBB and astroglial function.

Cerebrovascular ultrastructural alterations after intra-arterial infusions of ouabain, scilla-glycosides, heparin and histamine.

Cardiac glycosides which inhibit Na/K-ATPase (ouabain, scilliroside, scillirosidin) as well as heparin and histamine were infused into a cannulated branch of the middle cerebral artery or by isolated head perfusion in cats and dogs. Ouabain permeating the blood-brain barrier (BBB) caused the same selective swelling of astrocytes and of certain presynaptic elements as after direct application to the brain tissue. The other cellular elements of brain tissue and the vascular endothelium did not react, although the latter was exposed to the highest drug concentrations (about 10-3 M ouabain). By the swelling about one third of the capillaries became more or less constricted accompanied by an increase in endothelial vesiculation and in the number of osmiophilic inclusions in all cells of the vascular wall and of the pericapillary tissue. Osmiophilic material resembling plasma proteins occured in widened intercellular clefts indicating an increased BBB permeability after survival times (40 min). In contrast to the capillaries some terminal vessels are dilated which may correspond to shunt vessels causing an inhomogeneous, even increased cerebral blood flow after ouabain. Scilliroside and scillirosidin cause essentially the same changes as ouabain, but of smaller intensity and extent. In the present study, neither histamine nor heparin caused any structural change of the vessels or brain tissue.