The use of in vivo fluorescence image sequences to indicate the occurrence and propagation of transient focal depolarizations in cerebral ischemia.

A method for the detection and tracking of propagated fluorescence transients as indicators of depolarizations in focal cerebral ischemia is described, together with initial results indicating the potential of the method. The cortex of the right cerebral hemisphere was exposed for nonrecovery experiments in five cats anesthetized with chloralose and subjected to permanent middle cerebral artery (MCA) occlusion. Fluorescence with 370-nm excitation (attributed to the degree of reduction of the NAD/H couple) was imaged with an intensified charge-coupled device camera and digitized. Sequences of images representing changes in gray level from a baseline image were examined, together with the time courses of mean gray levels in specified regions of interest. Spontaneous increases in fluorescence occurred, starting most commonly at the edge of areas of core ischemia; they propagated usually throughout the periinfarct zone and resolved to varying degrees and at varying rates, depending on proximity of the locus to the MCA input. When a fluorescence transient reached the anterior cerebral artery territory, its initial polarity reversed from an increase to a decrease in fluorescence. An initial increase in fluorescence in response to the arrival of a transient may characterize cortex that will become infarcted, if pathophysiological changes in the periinfarct zone are allowed to evolve naturally.

Expression of endothelin(A) receptors in human gliomas and meningiomas, with high affinity for the selective antagonist PD156707.

OBJECTIVE: Endothelin (ET) immunoreactivity, ET production, and specific ET receptors have been identified in the brain. Changes in ET concentration or receptor expression have been implicated in the pathophysiological changes in vasospasm after subarachnoid hemorrhage and in cerebral neoplasia. In this study, we have characterized the ET(A) and ET(B) receptor subtypes present in human normal cerebral cortex (NCC) and two common central nervous system tumors, i.e., meningioma (MNG) and glioblastoma multiforme (GBM). A knowledge of the ET receptor subtypes present may provide a novel therapeutic target for newly developed ET antagonists. METHODS: Saturation, competition, and autoradiographic studies were performed with the subtype-specific radioligands 125I-PD151242 and 125I-BQ3020, to characterize the ET(A) and ET(B) receptors present in NCC, MNG, and GBM. RESULTS: NCC expresses high-affinity ET(A) receptors on pial and intraparenchymal vessels and high-affinity ET(B) receptors on glia and neurons. MNGs express mainly (85%) high-affinity ET(A) receptors in a diffuse pattern, whereas GBMs express high-affinity ET(A) receptors on the neovasculature and ET(B) receptors on the nonvascular elements. The ET antagonist PD156707 (Kd = 0.059 nmol/L) showed a higher affinity for the ET(A) receptor subtype than did bosentan (Kd = 1.1 nmol/L). CONCLUSION: ET(A) receptors are expressed in high concentrations in MNGs and in the vasculature of NCC and GBMs. The ET(A)-selective antagonist PD156707 may be of potential therapeutic value in vascular and neoplastic diseases of the central nervous system.

Gas in the cranium: an unusual case of delayed pneumocephalus following craniotomy.

We present the case history of a 23-year-old man who underwent frontal craniotomy followed by radiotherapy for a Grade III anaplastic glioma. Magnetic resonance imaging (MRI) at the 3-month follow-up showed significant tumour response. He became unwell some weeks after the MRI with an upper respiratory tract infection, severe headache and mild right-sided weakness. A computed tomographic (CT) scan showed a very large volume of intracranial gas, thought to have entered via a defect in the frontal air sinus after craniotomy and brought to light by blowing his nose. Intracranial air is frequently present after craniotomy, but it is normally absorbed within 34 weeks. The presence of pneumocephalus on a delayed postoperative CT scan should raise the possibility of a cerebrospinal fluid (CSF) fistula, or infection with a gas-forming organism. Many CSF fistulae require surgical closure in order to prevent potentially life-threatening central nervous system infection and tension pneumocephalitis. Immediate neurosurgical review is advisable.

A survey of the peri-operative management of patients undergoing anterior cervical decompression in the UK and Eire.

The peri-operative management of patients undergoing single level anterior cervical decompression (ACD) in neurosurgical departments in the UK and Eire has been surveyed. Eighty-eight per cent (132 of 150) of consultant neurosurgeons responded and of these 118 perform ACD. Nearly all (96%) respondents use interbody grafts and most of these use autologous bone (63%). A small minority (4%) never use interbody grafts. Forty-four per cent of surgeons use the same surgical technique irrespective of the underlying pathology (Cloward 57%: Smith Robinson 33%; ACD without graft 8%). Surgibone grafts are used by 25% and BOP grafts by 5%, but 15% of surgeons have abandoned artificial graft materials because of concerns about non-union. This survey has revealed a diverse range of practice amongst UK neurosurgeons. A prospective randomized trial is required to identify whether the theoretical benefits of interbody grafting following cervical discectomy justify donor site morbidity and the expense and risks of substitute graft materials.

Spinal cord compression from precipitation of drug solute around an epidural catheter.

We report a previously undescribed complication of long-term epidural catheter placement for the administration of analgesia in terminal malignancy. Spinal cord compression resulted from a drug-related precipitate forming around the epidural catheter tip, which was successfully treated by surgical decompression.

Modification of the standard pterional approach for aneurysms of the anterior circle of Willis.

A modification of the standard pterional approach for aneurysms of the anterior circulation is described. Our technique utilizes a smaller curvilinear skin incision, splitting the temporalis and a limited craniectomy. Reduced tissue dissection results in a smoother postoperative course and improves cosmesis without compromising neurological recovery. Minimal brain retraction is required as the technique allows the surgeon to make full use of the basal opening without temporalis muscle obscuring the view.

Subdural empyema in an HIV positive patient.

A subdural empyema with a Salmonella species as the likely causative organism is presented. We believe that this is the first reported case of such an infection in an HIV positive patient. The difficulties in treatment and diagnosis are discussed.

ETA receptors predominate in the human vasculature and mediate constriction.

Our aim was to identify which endothelin (ET) receptor subtypes are present in the human vasculature. We used subtype-selective radiolabeled ligands, [125I]-PD151242 and [125I]-BQ3020, to measure the ratio of endothelin ETA and ETB receptors in the media of blood vessels in human tissues including brain, kidney, heart, lung, and adrenal. In the brain, resistance vessels (diameter less than 300 micron) within the cortex and the pial arteries expressed only ETA receptors. In the kidney, high densities of ETA receptors were localized to the resistance vessels. A small population of ETB receptors was detectable in larger diameter vessels; the ratios of ETA: ETB were 90:10 (renal artery), 92:8 (renal vein), and 95:5 (arcuate artery). In the heart, only ETA receptors could be detected within intramyocardial resistance vessels. A small number of ETB receptors (less than 15%) were found in epicardial coronary arteries and aorta removed from patients with atherosclerosis, but ETB receptors were difficult to detect in normal vessels. In the adrenal, ETA receptors also predominated in arteries of the capsular plexus (87:13), central medullary vein (85:15), and resistance vessels. ETB receptors also represented less than 15% of the ET receptors in the pulmonary artery, internal mammary artery, and saphenous vein. The results show a consistent pattern, with only ETA receptors detected in resistance vessels in these tissues. In the larger arteries and veins, the ETB subtype represents a maximum of about 15% of the ET receptors. We have previously shown in human arteries and veins that ET-1 mediates vasoconstriction via the ETA subtype. The results suggest that ET-1-induced constriction would also occur via the ETA subtype in the smaller resistance vessels, as ETB receptors could not be detected.

Characterization of endothelin receptors in human brain cortex, gliomas, and meningiomas.

We have characterized the endothelin (ET) receptor subtypes present within normal human cerebral cortex (CC), glioblastoma multiforme (GBM), and meningiomas (MGs), using two subtype-selective radioligands, [125I]-PD151242 (ETA) and [125I]-BQ3020 (ETB). For saturation experiments, sections of tissue were incubated with increasing concentrations (8 pM-4 nM) of either [125I]-PD151242 or [125I]-BQ3020 in incubation buffer (22 degrees C, 2 h). In saturation binding assays, [125I]-PD151242 bound with high affinity to a single population of ET receptors (n = individuals; +/- SEM) in normal CC (n = 3; Kd 1.23 +/- 0.20 nM; Bmax 28.10 +/- 9.04 fmol/mg protein), GBM (n = 5; Kd 1.62 +/- 0.20 nM; Bmax 147.04 +/- 62.8 fmol/mg protein), and MGs (n = 3; Kd 3.10 +/- 0.44 nM; Bmax 290.3 +/- 105.8 fmol/mg protein). [125I]-BQ3020 also bound with high affinity to a single population of ET receptors in normal CC (n = 3; Kd 4.54 +/- 1.58 nM; Bmax 190.5 +/- 88.8 fmol/mg protein), GBM (n = 4; Kd 1.38 +/- 0.28 nM; Bmax 234.0 +/- 153.6 fmol/mg protein), and MGs (n = 3; Kd 0.25 +/- 0.09 nM; Bmax 22.8 +/- 18.0 fmol/mg protein). To determine receptor subtype localization, autoradiography was performed after incubation of sections with 0.1 nM [125I]-ET-1 (ETA and ETB), [125I]-PD151242 (ETA), and [125I]-BQ3020 (ETB). Autoradiography demonstrated a high concentration of ETA receptors within the pial and intraparenchymal vessels and meninges overlying the CC. Gray and white matter were diffusely ETB-positive. GBM had a strongly vascular pattern of ETA distribution. ETA receptors were dense and homogeneous in MGs. [125I]-PD151242 binds with high affinity to human pial and intraparenchymal vessels and is able to clearly delineate the microvasculature in GBM. Selective ETA receptor manipulation may have potential benefits in cerebrovascular disease and neoplasia without producing detrimental effects on the predominantly ETB-positive brain parenchyma.