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Biomedical subjects

Marc R Mayberg

Publications and source records attributed to Marc R Mayberg.

25 records · Page 2Linked to original sources
PubMed2003

Peripheral markers of brain damage and blood-brain barrier dysfunction.

PURPOSE: Occurrence of brain damage is frequently associated with abnormal blood-brain barrier (BBB) function. Two brain-specific proteins, S100beta and neuron-specific enolase (NSE) are released systemically in a variety of neurological diseases, but S100beta levels sometimes rise in the absence of neuronal damage, suggesting that S100beta is a marker of BBB rather than neuronal damage. METHODS: We measured both proteins in the serum of patients undergoing iatrogenic BBB disruption with intrarterial mannitol, followed by chemotherapy. RESULTS: Serum S100beta increased significantly after mannitol infusion (p<0.05) while NSE did not. Furthermore, in a model of intracerebral hemorrhage, S100beta increases in CSF did not lead to serum changes at a time when the BBB was intact. Modeling of S100beta release from the CNS suggested that low (<0.34 ng/ml) serum levels of S100beta are consistent with BBB opening without CNS damage, while larger increases imply synthesis and release from presumable damaged glia. CONCLUSIONS: Thus, S100beta in serum is an early marker of BBB openings that may precede neuronal damage and may influence therapeutic strategies. Secondary, massive elevations in S100beta are indicators of prior brain damage and bear clinical significance as predictors of poor outcome or diagnostic means to differentiate extensive damage from minor, transient impairment.

Animals↗
PubMed2002

A new dynamic in vitro model for the multidimensional study of astrocyte-endothelial cell interactions at the blood-brain barrier.

Blood-brain barrier endothelial cells are characterized by the presence of tight intercellular junctions, the absence of fenestrations, and a paucity of pinocytotic vesicles. The in vitro study of the BBB has progressed rapidly over the past several years as new cell culture techniques and improved technologies to monitor BBB function became available. Studies carried out on viable in vitro models are set to accelerate the design of drugs that selectively and aggressively can target the CNS. Several systems in vitro attempt to reproduce the physical and biochemical behavior of intact BBB, but most fail to reproduce the three-dimensional nature of the in vivo barrier and do not allow concomitant exposure of endothelial cells to abluminal (glia) and lumenal (flow) influences. For this purpose, we have developed a new dynamic in vitro BBB model (NDIV-BBB) designed to allow for extensive pharmacological, morphological and physiological studies. Bovine aortic endothelial cells (BAEC) developed robust growth and differentiation when co-cultured alone. In the presence of glial cells, BAEC developed elevated Trans-Endothelial Electrical Resistance (TEER). Excision of individual capillaries proportionally decreased TEER; the remaining bundles were populated with healthy cells. Flow played an essential role in EC differentiation by decreasing cell division. In conclusion, this new dynamic model of the BBB allows for longitudinal studies of the effects of flow and co-culture in a controlled and fully recyclable environment that also permits visual inspection of the abluminal compartment and manipulation of individual capillaries.

Algorithms↗
PubMed2002

Mechanisms of endothelial survival under shear stress.

Endothelial cells (ECs) are exposed to cytotoxic reactive oxygen species and oxidation products of NO, yet they are characterized by low apoptotic rates and have an average life span of many years. EC exposure to flow has been shown to downregulate cell cycle-related genes and cause cytoskeletal rearrangement. We hypothesized that exposure to flow also causes molecular and physiological changes that induce antioxidant properties in ECs. We used cDNA array expression profiling and protein analysis to study the responses of human ECs exposed to flow in a hollow fiber apparatus or the same ECs grown under static conditions. Our results show that shear-induced synchronized expression of processes control oxidant production; these changes included upregulation of NADH-producing enzymes (Krebs cycle dehydrogenases and glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) accompanied by simultaneous decrease in NADH-depleting pathways (e.g., lactate dehydrogenase [LDH]) and diminished production of lactate. Exposure to flow upregulated cytoskeletal genes. Our results suggest that, in addition to inhibition of cell cycle, exposure to flow influences ECs by controlling expression of enzymes involved in the generation of antioxidant intermediates and in adaptive control of cell shape. These changes may explain longevity and antioxidant efficiency of ECs and may provide insight in mechanisms leading to pathological conditions such as arteriosclerosis.

Biomechanical Phenomena↗
PubMed2002

Sustained arterial narrowing after prolonged exposure to perivascular endothelin.

OBJECTIVE: The vasoconstrictor peptide endothelin-1 (ET-1) produces narrowing of cerebral arteries and has been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. Little is known, however, regarding the physiological consequences of prolonged exposure of arterial wall to ET-1. METHODS: In 30 rats, normal saline or 10(-8) mol/h of ET-1 was continuously applied for 3 or 5 days to the adventitial surface of the femoral artery in a Silastic cuff via an osmotic infusion pump. Vessels were examined for histopathological changes and luminal narrowing during ET-1 infusion (3 or 5 d) or at intervals from 2 to 9 days after infusion was stopped. RESULTS: Marked arterial constriction (30-40% arterial diameter reduction) was present during continuous ET-1 infusion for 3 or 5 days. For both 3- and 5-day ET-1 infusions, significant reduction in arterial cross sectional area persisted up to 4 days after cessation of infusion, after which normal caliber returned. In arteries with persistent luminal narrowing after cessation of ET-1 infusion, light microscopic findings revealed morphological changes in the vessel wall similar to those observed in cerebral vasospasm after subarachnoid hemorrhage, with apparent increased collagen deposition in media and adventitia. CONCLUSION: Continuous infusion of ET-1 produces reversible arterial narrowing that persists beyond the usual interval of physiological effect for this agent. Prolonged arterial constriction may produce physiological changes in arterial wall that act to maintain a narrowed lumen.

Animals↗
PubMed2002

Delayed facial palsy after resection of vestibular schwannoma.

OBJECT: In this study the authors investigate delayed facial palsy (DFP), which is an underreported phenomenon after surgery for vestibular schwannoma (VS). The authors identified 15 (4.8%) patients from a consecutive series of 314 who underwent surgery for VS between 1988 and 2000, and in whom DFP developed. Delayed facial palsy was defined as a deterioration of facial nerve function from House-Brackmann Grades 1 or 2 more than 3 days postoperatively. METHODS: All patients underwent intraoperative neurophysiological monitoring of facial nerve function. The average latency of DFP was 10.9 days (range 4-30 days). In six patients (40%) minor deterioration (< or = two House-Brackmann grades) had occurred at a mean of 10.2 days postsurgery, whereas in nine patients (60%) moderate deterioration (> or = three House-Brackmann grades) had occurred at a mean of 11.8 days postoperatively. Five (33%) of 15 patients recovered to Grade 1 of 2 function within 6 weeks of DFP onset. Of the 15 patients with DFP, 14 had completed 1 year of follow up at the time of this study. Twelve (80%) of these 15 patients recovered to Grade 1 or 2 function within 3 months, and 13 (93%) of 14 patients recovered within 1 year. In all cases, stimulation of the seventh cranial nerve on completion of tumor resection revealed the nerve to be intact, both anatomically and functionally, to proximal and distal stimulation at 0.1 mA. A smaller tumor diameter correlated with greater recovery of facial nerve function. There was no correlation between the latency or severity of or recovery from DFP, and the patient's age or sex, the surgical approach, frequency of neurotonic seventh nerve discharges, anatomical relationship of the facial nerve to the tumor, patient's history of tobacco use, or cardiovascular disease. CONCLUSIONS: It appears that DFP is an uncommon consequence of surgery for VS. Although excellent recovery of facial nerve function to its original postoperative status nearly always occurs after DFP, the magnitude and time course of the disorder were not predictors for subsequent recovery of facial nerve function.

Adolescent↗
PubMed2002

Intracranial navigation by using low-field intraoperative magnetic resonance imaging: preliminary experience.

OBJECT: Intracranial navigation by using intraoperative magnetic resonance (iMR) imaging allows the surgeon to reassess anatomical relationships in near-real time during brain tumor surgery. The authors report their initial experience with a novel neuronavigation system coupled to a low-field iMR imaging system. METHODS: Between October 2000 and December 2001, 70 neurosurgical procedures were performed using the mobile 0.12-tesla PoleStar N-10 iMR imaging system. The cases included 38 craniotomies, 15 brain biopsies, nine transsphenoidal approaches, and one drainage of a subdural hematoma. Tumor resection was performed using the awake method in seven of 38 cases. Of the craniotomies, image-confirmed complete or radical tumor resection was achieved in 28 cases, subtotal resection in eight cases, and open biopsies in two cases. Tumor resection was controlled with the use of image guidance until the final intraoperative images demonstrated that there was no residual tumor or that no critical brain tissue was at risk of compromise. In each stereotactic biopsy the location of the biopsy needle could be verified by intraoperative imaging and diagnostic tissue was obtained. Complications included a case of aseptic meningitis after a biopsy and one case of temporary intraoperative failure of the anesthesia machine. Awake craniotomies were performed successfully with no permanent neurological complications. CONCLUSIONS: Intraoperative MR image-based neuronavigation is feasible when using the Odin PoleStar N-10 system for tumor resections that require multiple other surgical adjuncts including awake procedures, cortical mapping, monitoring of somatosensory evoked potentials, or electrocorticography. Use of the system for brain biopsies offers the opportunity of immediate verification of the needle tip location. Standard neurosurgical drills, microscopes, and other equipment can be used safely in conjunction with this iMR imaging system.

Adult↗