Pituitary-brain vascular relations: a new paradigm.

Vascular casts of the pituitary gland have demonstrated a paucity of veins extending from the adenohypophysis to the systemic circulation and have suggested that some adenohypophyseal venous blood returns to the neurohypophysis. The neurohypophyseal capillary bed may function as a vascular switch and in this article a series of 14 questions are proposed regarding the vascular dynamics of the pituitary. Together these questions raise the larger question, namely, whether pituitary hormones are transported directly to the brain to modify brain function?

Can the pituitary secrete directly to the brain? (Affirmative anatomical evidence).

Vascular casts of 10 rhesus monkey pituitary glands and three vascular casts of the rhesus monkey cavernous sinus were examined by scanning electron microscopy. A continuous neurohypophyseal capillary bed was found uniting the infundibulum, infundibular stem, and infundibular process. The neurophypophysis was supplied by three groups of arteries: superior hypophyseal, middle hypophyseal, and inferior hypophyseal. Numerous anastomoses were found between individual arteries, and some hypophyseal arteries formed anastomotic links between different portions of the circle of Willis. Veins located at the caudal pole of the infundibular process, capillaries linking the infundibulum to the hypothalamus, and portal vessels extending from the infundibulum to the adenohypophysis provided efferent vascular pathways from the neurohypophysis. The adenohypophysis received no direct arterial supply; its entire afferent vascular supply was provided by portal vessels. Lateral hypophyseal veins were not found; small adenohypophyseal veins joined larger neurohypophyseal veins to form confluent pituitary veins which extended to the cavernous sinus. The capacity of the venous connections draining the adenohypophysis directly to the cavernous sinus appeared small when compared to that of of the long portal vessels supplying the adenohypophysis. However, many of the short portal vessels interposed between the adenohypophysis and the infundibular stem and process were well arranged to function as alternative efferent routes from the adenohypophysis. The limited potential for venous drainage directly to the cavernous sinus suggests that blood leaves the adenohypophysis by other routes; blood carried via long portal vessels from the infundibulum to the adenohypophysis may return to the neurohypophyseal capillary bed via short portal vessels. This anatomical study suggests that hypothalamic and adenohypophyseal secretions are conveyed to the capillary bed of the neurohypohysis. These secretions may leave the neurohypophysis via any of seven potential routes: one efferent route is directed to the adenohypophysis, another route is directed to the systemic circulation, but five of the potential efferent routes are directed toward the brain.

Regional cerebral and neural lobe blood flow during insulin-induced hypoglycemia in unanesthetized rats.

The effects of hypoglycemia on regional cerebral blood flow (rCBF) were studied in awake restrained rats. The rats were divided into three groups consisting of a normoglycemic control group that received only saline, a hypoglycemic group A, which was given insulin 30 min before flow was measured, and a hypoglycemic group B, which was given insulin 90 and 30 min before flow was measured. Regional CBF was measured using 14C-iodoantipyrine. Mean plasma glucose was 8.76 mumol/ml in the control group, 2.63 mumol/ml in hypoglycemic group A, and 1.51 mumol/ml in hypoglycemic group B. Plasma epinephrine and norepinephrine concentrations increased to approximately 375% and 160%, respectively, of control values in hypoglycemic groups A and B. In the hypoglycemic group A, rCBF significantly increased in three brain regions. In the hypoglycemic group B, rCBF increased significantly in all brain regions measured, with the exception of the neural lobe, in which it decreased. The increase in rCBF ranged from 38% in the hypothalamus to 138% in the thalamus. Neural lobe blood flow significantly decreased by 31%. The neural lobe was the only brain region studied that is not protected by a blood-brain barrier. It may be sensitive to changes in the concentration of vasoactive agents in blood, such as epinephrine and norepinephrine.

Neurohemal contact in the internal zone of the rabbit median eminence.

The concept of neurosecretion as the mechanism by which neural control of adenohypophyseal function is accomplished was based on the observation that long capillary loops penetrate deeply into the supraopticohypophyseal tract as it passes through the median eminence internal zone. However, neural contact upon these capillary loops has not been demonstrated in the mammalian median eminence. The present transmission electron microscopic investigation of the rabbit median eminence demonstrates neurohemal contact in the median eminence internal zone. Axons containing small lucent vesicles 53.3 +/- 3.28 nm in diameter (mean +/- SEM) or small lucent and large granular vesicles with a mean diameter of 122.4 (+/- 3.28 nm) in their terminals make neurohemal contact with capillary loops in the internal zone and form a cuff about them. These terminals resemble terminals found in the external zone. Intravenous injection of the false neurotransmitter 5-hydroxydopamine (5-OH-DA) renders small lucent vesicles granular in both the external and internal zone. The effect of 5-OH-DA injection is abolished by concurrent reserpine administration. Whereas large granular vesicles in many terminals become lucent after reserpine administration, in others they remained electron dense. Viewed in the light of previous studies our findings suggest that the internal plexus arises from the external plexus and invaginates the neuropil carrying connective tissue and parvicellular axon terminals of aminergic and peptidergic systems from the external zone into the internal zone, that some elements making neurohemal contact with long capillary loops are terminals of the noradrenergic reticular infundibular tract arising outside the hypothalamus in the brainstem, and that long capillary loops form a system of repeating microvascular modules which markedly increase the surface available for neurohemal contact.

Patterns of degeneration in the external cuneate nucleus after multiple dorsal rhizotomies.

Unilateral, intradural dorsal rhizotomies (C3-Cs) were performed on adult rats to study the patterns of synaptic organization of ascending dorsal root fibers in the external cuneate nucleus (ECN). Animals were permitted to survive for periods of time ranging from 3 hours to 12 days. Sham-operated animals presented a morphology indistinguishable from that of normal, unoperated animals. In rhizotomized animals, degeneration was observed ipsilaterally at all survival periods. After postoperative survivals of 3 to 14 hours some terminal boutons displayed clumping and diminution in numbers of synaptic vesicles and, in addition, degeneration myelinated axons were observed at this time. There was considerable degeneration in the neuropil between 24 and 48 hours postoperative. Two forms of degeneration occurred in axons and terminal boutons with comparable frequency: electron lucent degeneration and electron opaque degeneration. Reactive phagocytic glial cells contained degenerated masses, lipoid droplets, lysosome-like structures and myelin fragments. After postoperative survivals of four to six days, lucent and opaque degenerating terminals were less numerous. Neurofilamentous degeneration was observed only occasionally. Unaltered synaptic membrane specializations were present and were usually abutted by glia. At 12 days postoperative, synaptic glomeruli and serial synapses were not seen. Invaginating dendritic spines were rarely seen. Bouton populations that remained unualtered were: small (0.3-3.0 micron) boutons that contact dendritic shafts and somata, nodal synaptic boutons and boutons containing granular vesicles (80-100 nm).

Optic neuropathy and paratrigeminal syndrome due to Aspergillus fumigatus.

Chronic Aspergillus meningitis and cerebral vasculitis occurred in a 67-year-old man. He experienced periorbital pain that increased in severity during a ten-month period. Although no focal neurologic deficits were initially present, oculosympathetic paresis, corneal hypesthesia, and optic neuropathy developed. This is the first report, to our knowledge, of paratrigeminal syndrome with optic neuropathy due to aspergillosis. The case was also unusual because it was chronic and there was no extracerebral infection or predisposing factors, such as underlying malignancy or collagen vascular disease.

Optic nerve blood flow and its regulation.

Intracranial optic nerve blood flow was measured by the radiolabeled microsphere technique in 30 adult sheep under light barbiturate anesthesia. Regional blood-flow rates were determined under basal conditions. The responses of regional blood flow to alterations in PaCO2 and to changes in arterial blood pressure were also measured. Under basal conditions blood flow was comparable to that found in other cerebral white matter (14 +/- 1 ml/100 gm/min). Responses to hypercarbia and hypocarbia were also similar to reported measurements for other cerebral white matter. With alteration of arterial blood pressure, intracranial optic nerve blood flow remained constant within the limits of cerebral autoregulation.

Computed alignment of dissimilar images for three-dimensional reconstructions.

Three-dimensional reconstructions from serial section images require the accurate registration of those images. Image correlation is the most powerful computed alignment method and its performance on identical images, or parts thereof, has been thoroughly studied. Correlation alignments of complex, dissimilar images can fail, however, with a likelihood proportional to the magnitude of the differences. We report that alignments can be computed more reliably and more accurately (higher-valued correlation coefficients) by the combined use of lowpass-filtered product transforms (from which the correlation functions are formed), autocorrelation correction of rotational misalignment, and covariance correction of translation misalignment. A simple rule is proposed for the lowpass filter cutoff radius depending on measures of the images' differences. These methods are demonstrated with a reconstruction of a capillary loop in the median eminence of the hypothalamus.

Choroid plexus blood flow in the sheep.

Choroid plexus blood flow was measured in 29 adult female sheep using the radioactive microsphere technique. Basal blood flow, response to change in arterial carbon dioxide tension, and response to change in mean arterial blood pressure were determined. The results were compared to cerebral cortical blood flow values in the same sheep. Mean choroid plexus blood flow was 601 ml/100 g/min under basal conditions. Choroid plexus blood flow fell 31% with hypocarbia, a reduction comparable to that seen in cortex. With hypercarbia choroid plexus blood flow rose only 27% whereas cortical blood flow increased by 199%. Unlike cortical blood flow, choroid plexus blood flow fell significantly with pharmacogenic hypertension. The latter finding may reflect the absence of a blood-brain barrier in choroid plexus.

Blood flow and functional responses correlate in the ovine neural lobe.

Regional neurohypophyseal and cerebral blood flow were measured in 5 awake unstressed female sheep with radiolabelled microspheres before and after the intracarotid infusion of a 3% NaCl solution. Plasma arginine vasopressin (AVP) levels were concurrently measured by radioimmunoassay. Following intracarotid sodium chloride infusion, neural lobe (but not median eminence) blood flow significantly increased, as did plasma AVP levels. Directed thirst and water-seeking behavior was observed, accompanied by a global increase in cortical blood flow. We conclude that the neuroendocrine response and the behavioral display induced by intracarotid sodium chloride infusion are accompanied by increases in blood flow in selected brain regions.

Choroid plexus blood flow: evidence for dopaminergic influence.

Choroid plexus blood flow was measured in adult female sheep using the radioactive microsphere technique. The response of choroid plexus, renal and cortical blood flow to the infusion of dopamine (11 sheep), haloperidol (7 sheep) and propranolol (6 sheep) were compared. Choroid plexus and renal blood flow significantly increased after dopamine infusion (55% and 49% respectively). Choroid plexus and renal blood flow decreased significantly following haloperidol infusion (-24% and 29% respectively). Cortical blood flow did not significantly change. Propranolol infusion did not significantly change blood flow in these regions. These observations suggest that dopaminergic mechanisms play a role in the regulation of choroid plexus as well as renal blood flow.

Technical note: the use of nitroglycerin ointment after precarious neurosurgical wound closure.

It is suggested that the application of nitroglycerin ointment to neurosurgical wound closure exhibiting skin pallor or cyanosis can minimize necrosis and dehiscence. Examples of the use of this agent in patients undergoing myelomeningocele closure as well as in a premature infant undergoing ventriculoperitoneal shunting are described.

Scanning electron microscopy of the ventricular system in normal and hydrocephalic rabbits. Preliminary report and atlas.

The author used the scanning electron microscope to study the ependyma in six control rabbits and six rabbits made hydrocephalic by infusion of silicone oil into the cisterna magna. The ependymal lining of the third ventricle, head of the caudate nucleus, superior angle of the caudate, and atrium of the lateral ventricle was examined. In the hydrocephalic animals, clusters of cilia emanating from the ependyma over periventricular white matter become separated; the author believes this is secondary to ingrowth of new ependymal cell processes covered with microvilli. The addition of these cells to the ependymal surface permits ventricular dilatation without ependymal disruption and provides more surface containing microvilli, presumably capable of increased transventricular fluid transfer. No such changes occur over gray matter masses since their surfaces are not deformed by moderate ventricular dilatation. The morphological alterations in the ependyma that occur in moderate hydrocephalus do not appear to be simply manifestations of ependymal destruction but rather suggest a modification in its function from that of a surface capable of propelling cerebrospinal fluid to one capable of increased transfer of transventricular fluid. As hydrocephalus progresses, compensation may fail because of the relative decrease in microvilli so that the cell surface provides a less efficient mechanism for absorption.

Ganglion cell-containing tumors of the pituitary gland.

The ganglion cell-containing tumors of the pituitary are rare lesions of undetermined histogenesis and nosology. A review of the literature revealed 42 such tumors, including the 3 cases described below. On the basis of this review, the tumors were divided into two histologic groups, one consisting of both adenomatous and gangliocytic elements (32 cases), and the other of the gangliocytic component only (10 cases). The first group of tumors were more common in females (23 of 32 cases) and were often active endocrinologically (28 of 32 cases), and acromegaly was the most common manifestation (19 cases). The second group was also more common in females (7 of 10 cases) but was less frequently active endocrinologically (3 of 19 cases). We review histologic and immunocytochemical findings in these tumors and discuss their histogenesis. We propose that the term mixed pituitary adenoma-gangliocytoma be used for the first group and gangliocytoma for the second. The two groups should be kept separate until their histogenesis is better understood.

The surgical workstation: surgical planning using generic software.

Computer software for rendering and display of three-dimensional data is becoming readily available for all types of computers. Such programs typically accept data from any source, compute a three-dimensional volume of data, and display it with a variety of rendering options. Although not specifically designed for medical image processing, these programs can provide very detailed and finely rendered images that are useful for surgical planning. We use one such program to display data from standard computed tomography scans, which gives us a photorealistic three-dimensional view of patient anatomy. This view can be modified to render tissues transparent, translucent, or opaque, and thus allows the surgeon to selectively enhance bony architecture, tumors, or other details. Images can be rotated, sliced, and displayed in the surgical position. Image animation can be added to facilitate the display of complex anatomic relationships. Our experience with this technology suggests that such programs can provide the basis for personal surgical workstations for medical image analysis and surgical planning. Further development of such generic imaging systems should allow this useful technology to become widely available for surgical planning and education. We discuss our experience with a typical generic imaging workstation.

Radionuclide blood flow studies before and after gelfoam embolization of intracranial meningiomas.

Radionuclide blood flow studies were employed to evaluate the success or failure of preoperative Gelfoam embolization in two patients with intracranial meningiomas. In both cases, the initial radionuclide blood flow study showed tumor visualization during the arterial phase. Immediately following the embolization procedure, the radionuclide blood flow study showed no visualization of the meningioma during the arterial phase, indicating a successful embolization procedure in preparation for removal of the tumor in a relatively bloodless field.

Three-dimensional reconstruction of median eminence microvascular modules.

To test the hypothesis that the median eminence microvasculature has a direct regulatory role in the hormonal communication between the brain and the pituitary gland, it is necessary to determine whether the physical means for such control (e.g. smooth muscle sphincters strategically located in the capillary plexus) actually exists. Our approach is to search for such structures in transmission electron micrographs of thin serial sections of the median eminence. The complexity of these images and the anticipated need to include large numbers of them in the study led us to consider computer reconstruction for this problem. We report here the successful three-dimensional reconstruction of capillary modules using digital image processing techniques for capillary feature detection/extraction, for construction of montages (mosaics) of overlapping images of the same section, and for automatic image registration by two independent methods without the use of fiducial marks. These tasks have been performed manually in nearly all the published neurobiological reconstructions; here they are performed by programs using only the mathematical properties of the images. Methods like those described here provide the only practical means for executing large scale reconstructions and gaining significant new information about the regulation of blood flow in this region of the brain.