Syringomyelia.

Syringomyelia is not a single disease, but rather a descriptive term for any fluid cavity in the spinal cord. Regardless of the underlying etiology, the signs and symptoms of syringomyelia are related to the location, size, and extent of the cavity. With the advent of magnetic resonance imaging (MRI) and improved surgical procedures for decompression of the cavity, syringomyelia is an increasingly recognized cause of disability and even death in patients with clinical signs and symptoms of central spinal cord lesions. In this review, the etiology, pathophysiology, imaging, and treatment will be concisely discussed.

Stereospecific transport of Tyr-MIF-1 across the blood-brain barrier by peptide transport system-1.

Previous studies have suggested that peptide transport system-1 (PTS-1), the saturable system that transports Tyr-MIF-1, the enkephalins, and related peptides out of the central nervous system (CNS), exhibits stereospecificity. In the present studies, we showed that 125I-L-Tyr-MIF-1, but not 131I-D-Tyr-MIF-1, was cleared from the CNS more rapidly than could be accounted for by nonspecific mechanisms. Such clearance was inhibited by a 1.0 nmol dose of L-Tyr-MIF-1, but not by D-Tyr-MIF-1. Neither L- nor D-Tyr-MIF-1 altered the much lower clearance of I-D-Tyr-MIF-1 from the brain. Radioactivity recovered from the vascular space after the injection of 125I-Tyr-MIF-1 into the lateral ventricle of the brain eluted by HPLC primarily as intact peptide, demonstrating that most of the Tyr-MIF-1 was not degraded during transport. By contrast, the nonsaturable unidirectional influx of Tyr-MIF-1 into the CNS did not distinguish between the isomers. These studies confirm and extend the observations that Tyr-MIF-1 is transported out of the CNS by a saturable, stereospecific transport system as an intact peptide while the influx into the CNS is by a nonsaturable mechanism that does not distinguish between the isomers.

Tyr-MIF-1 and Met-enkephalin share a saturable blood-brain barrier transport system.

Previous studies have shown that methionine enkephalin and Tyr-MIF-1 are transported from the brain to the blood by a saturable, stereospecific, carrier-mediated process. It was not established by these studies whether Tyr-MIF-1 and methionine enkephalin were transported by the same system or by separate, but overlapping systems. This issue was investigated in anesthetized mice receiving injections containing both 131I-methionine enkephalin and 125I-Tyr-MIF-1 into the lateral ventricle of the brain. Mice were decapitated and the brain to blood transport rate was derived from the residual counts in the brain. It was found that in individual mice, the transport rate for Tyr-MIF-1 correlated highly with the transport rate for methionine enkephalin but not with the transport of iodide. This shows that the transport of Tyr-MIF-1 is closely coupled to the transport of methionine enkephalin but dissociable from the brain to blood transport of iodide. Furthermore, the inability of varying doses of Tyr-MIF-1 or of methionine enkephalin to preferentially self-inhibit is radiolabeled form in comparison with the other peptide shows that, functionally, only a single system exists. Aluminum, a noncompetitive inhibitor of Tyr-MIF-1 transport, was also without preferential inhibition. Thus, under the conditions of these studies, only a single system could be functionally demonstrated for the transport of both Tyr-MIF-1 and methionine enkephalin.

Carrier-mediated transport of vasopressin across the blood-brain barrier of the mouse.

A brain to blood carrier-mediated transport system for arginine vasopressin (AVP) was investigated in mice after intraventricular injection of iodinated AVP and varying amounts of unlabeled material or candidate inhibitors. Residual activity in the brain detected after decapitation was used as the main determinant of transport activity. The half-time disappearance of iodinated AVP from the brain was 12.4 min, the Vmax was 1.41 nmol/g-min, and the apparent Km was 28.7 nmol/g. A 30-nmol dose of AVP, mesotocin, arginine vasotocin, pressinoic amide, pressinoic acid, tocinoic acid, and lysine vasotocin, but not oxytocin, lysine vasopressin, AVP free acid, tocinoic amide, Tyr-MIF-1, or cyclo Leu-Gly, significantly (P less than 0.05) inhibited the transport of iodinated AVP out of the brain. The 30 nmol dose of AVP had no effect on the transport of iodide or iodotyrosine out of the brain. High-performance liquid chromatography showed that 59.2% of the radioactivity found in the blood 2 min after an i.c.v. injection of labeled AVP eluted at the same position as labeled AVP compared with 68.8% of radioactivity eluting at that position after material was infused i.v. for 2 min. This indicates that intact peptide is transported across the blood-brain barrier and that most of the degradation of AVP occurs during circulation in the blood. Calculations based on the appearance of radioactivity in the periphery showed that 56.2% of the material injected centrally would have been transported into the periphery by 10 min. This appearance of material in the periphery was inhibited by the simultaneous injection of an excess of unlabeled peptide. Water loading significantly decreased the brain to blood transport rate of AVP by 40%. It is concluded that a saturable system exists for brain to blood transport of AVP and some structurally similar peptides.

Transport of thyroxine across the blood-brain barrier is directed primarily from brain to blood in the mouse.

The role of the blood-brain barrier (BBB) in the transport of thyroxine was examined in mice. Radioiodinated ("hot") thyroxine (hT4) administered icv had a half-time disappearance from the brain of 30 min. This increased to 60 min (p less than 0.001) when administered with 211 pmole/mouse of unlabeled ("cold") thyroxine (cT4). The Km for this inhibition of hT4 transport out of the brain by cT4 was 9.66 pmole/brain. Unlabeled 3,3',5 triiodothyronine (cT3) was unable to inhibit transport of hT4 out of the brain, although both cT3 (p less than 0.05) and cT4 (p less than 0.05) did inhibit transport of radioiodinated 3,3',5 triiodothyronine (hT3) to a small degree. Entry of hT4 into the brain after peripheral administration was negligible and was not affected by either cT4 nor cT3. By contrast, the entry of hT3 into the brain after peripheral administration was inhibited by cT3 (p less than 0.001) and was increased by cT4 (p less than 0.01). The levels of the unlabeled thyroid hormones administered centrally in these studies did not affect bulk flow, as assessed by labeled red blood cells (99mTc-RBC), or the carrier-mediated transport of iodide out of the brain. Likewise, the vascular space of the brain and body, as assessed by 99mTc-RBC, was unchanged by the levels of peripherally administered unlabeled thyroid hormones. Therefore, the results of these studies are not due to generalized effects of thyroid hormones on BBB transport. The results indicate that in the mouse the major carrier-mediated system for thyroxine in the BBB transports thyroxine out of the brain, while the major system for triiodothyronine transports hormone into the brain.