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W Stummer

Publications and source records attributed to W Stummer.

At least 19 recordsLinked to original sources
PubMed2006

Supratentorial meningeal melanocytoma mimicking a convexity meningioma.

OBJECTIVE AND IMPORTANCE: Meningeal melanocytomas are rare benign neuro-ectodermal tumors arising from melanocytic cells in the leptomeninges. These leptomeningeal melanocytes are found at highest density underneath the brain stem and along the upper cervical spinal cord. Thus, most reported cases of meningeal melanocytomas are located in the posterior fossa and the spinal cord, respectively. CLINICAL PRESENTATION: We report on the rare case of a 55-year-old male patient with a large supratentorial meningeal melanocytoma mimicking a convexity meningioma and a smaller, similarly dura based lesion in the posterior fossa. INTERVENTION: Tumor control to date was achieved by surgery of the large lesion and radiosurgery of the small lesion. CONCLUSION: Complete tumor resection may be advantageous and second or recurrent lesions may be managed by repeat surgery or stereotactic radiosurgery.

Diagnosis, Differential↗
PubMed2005

Oedema formation in experimental photo-irradiation therapy of brain tumours using 5-ALA.

BACKGROUND: Five-aminolevulinic acid (5-ALA) induces the specific accumulation of photosensitising porphyrins in malignant gliomas and has been explored for photo-irradiation therapy of these tumours. However, information is unavailable on whether and to what extent this treatment modality may induce the formation of brain oedema, and how potential oedema might be treated. METHODS: Rats were implanted with C6 gliomas. Eight days later magnetic resonance images (MRI) were obtained. On day 9 rats received 100 mg 5-ALA/kg b.w. and were craniotomized for photo-irradiation of tumours 6 hours later (100 J/cm2, 635 nm argon-dye laser). Part of the animals was treated with daily dexamethasone injections (0.3 mg/kg), beginning 6 hours before phototherapy. 72 hours later, brains were removed and dissected according to tumour dimensions on pre-therapy MRI into "tumour", "brain around tumour" (BAT), residual cortex and basal ganglia, for measurements of water contents. Measurements were also performed in untreated animals with tumours, with or without steroid treatment and in control animals. An additional group of animals lacking tumours, with or without steroid treatment, underwent 5-ALA-phototherapy to determine effects on normal brain. RESULTS: C6 gliomas induced brain oedema, which responded to steroid treatment. 5-ALA-phototherapy resulted in additional oedema, which responded partly to steroids. 5-ALA-phototherapy of normal brain increased water content moderately in irradiated cortex. This oedema was also partly counteracted by steroids. CONCLUSIONS: Photo-irradiation therapy with 5-ALA induces oedema which is partly counteracted by steroid therapy. The possibility of steroid resistant oedema formation should be considered when planning human trials with this treatment modality.

Aminolevulinic Acid↗
PubMed2004

Prospective documentation and analysis of the pre- and early clinical management in severe head injury in southern Bavaria at a population based level.

Treatment of patients suffering from severe head injury is so far restricted to general procedures, whereas specific pharmacological agents of neuroprotection including hypothermia have not been found to improve the outcome in clinical trials. Albeit effective, symptomatic measures of the preclinical rescue of patients (i.e. stabilization or reestablishment of the circulatory and respiratory system) or of the early clinical care (e.g. prompt diagnosis and treatment of an intracranial space occupying mass, maintenance of a competent circulatory and respiratory system, and others) by and large constitute the current treatment based on considerable organizational and logistical efforts. These and other components of the head injury treatment are certainly worthwhile of a systematic analysis as to their efficacy or remaining deficiencies, respectively. Deficits could be associated with delays of providing preclinical rescue procedures (e.g. until intubation of the patient or administration of fluid). Delays could also be associated in the hospital with the diagnostic establishment of intracranial lesions requiring prompt neurosurgical intervention. By support of the Federal Ministry of Education and Research and under the auspices of the Forschungsverbund Neurotraumatology, University of Munich, a prospective system analysis was carried out on major aspects of the pre- and early clinical management at a population based level in patients with traumatic brain injury. Documentation of pertinent data was made from August 1998 to July 1999 covering a catchment area of Southern Bavaria (5.6 mio inhabitants). Altogether 528 cases identified to suffer from severe head injury (GCS < or = 8 or deteriorating to that level within 48 hrs) were enrolled following admission to the hospital and establishment of the diagnosis. Further, patients dying on the scene or during transport to the hospital were also documented, particularly as to the frequency of severe head injury as underlying cause of mortality. The analysis included also cases with additional peripheral trauma (polytrauma). The efficacy of the logistics and organization of the management was studied by documentation of prognosis-relevant time intervals, as for example until arrival of the rescue squad at the scene of an accident, until intubation and administration of fluid, or upon hospital admission until establishment of the CT-diagnosis and commencement of surgery or transfer to the intensive care unit, respectively. The severity of cases studied in the present analysis is evident from a mortality of far above 40% of cases admitted to the hospital, which was increased by about 20% when including prehospital mortality. The outcome data notwithstanding, the emerging results demonstrate a high efficacy of the pre- and early clinical management, as indicated by a prompt arrival of the rescue squad at the scene, a competent prehospital and early clinical management and care, indicative of a low rate of avoidable complications. It is tentatively concluded on the basis of these findings that the patient prognosis is increasingly determined by the manifestations of primary brain damage vs. the development of secondary complications.

Craniocerebral Trauma↗
PubMed2004

Estradiol stimulates vascular endothelial growth factor and interleukin-6 in human lactotroph and lactosomatotroph pituitary adenomas.

Estrogens are considered to be critically involved in lactotroph and lactosomatotroph pituitary tumor development. In addition to direct effects, estradiol-induced tumor formation may involve alterations in growth factor and cytokine production. We have studied whether estradiol stimulates the production of the angiogenic vascular endothelial growth factor and the potential tumor progression factor interleukin-6 in 5 lactotroph (LA) and 5 lactosomatotroph (LSA) human pituitary adenoma cell cultures. All tumors secreted heterogenous basal amounts of VEGF (18.0 +/- 1.4 to 425 +/- 26 pg/ml per 24 h) and IL-6 (18.1 +/- 1.5 to 604 +/- 17 pg/ml per 24 h). Estradiol (100 nM) significantly enhanced VEGF release in all LA and LSA cell cultures (47 to 168 % above basal). IL-6 secretion was stimulated in 3 out of 5 LA and in all LSA cell cultures (31 to 287 % above basal). In cell cultures obtained from tumors from which sufficient cells could be isolated, a dose-dependent effect of estradiol (1 to 100 nM) on VEGF and IL-6 production was observed. Stimulation of IL-6 and/or VEGF secretion by estradiol in the majority of human lactotroph and lactosomatotroph adenoma cell cultures studied, suggests that estrogens may contribute to adenoma expansion through the stimulation of these auto-/paracrine-acting adenoma progression factors.

Adult↗
PubMed2003

Transport of 5-aminolevulinic acid between blood and brain.

Little is known about the movement of 5-aminolevulinic acid (delta-aminolevulinic acid; ALA) between blood and brain. This is despite the fact that increases in brain ALA may be involved in generating the neuropsychiatric symptoms in porphyrias and that systemic administration of ALA is currently being used to delineate the borders of malignant gliomas. The current study examines the mechanisms involved in the movement of [(14)C]ALA across the blood-brain and blood-CSF barriers in the rat. In the adult rat, the influx rate constant (K(i)) for [(14)C]ALA movement into brain was low ( approximately 0.2 microl/g per min), was unaffected by increasing plasma concentrations of non-radioactive ALA or probenecid (an organic anion transport inhibitor) and, therefore, appears to be a diffusional process. The K(i) for [(14)C]ALA was 3-fold less than that for [(14)C]mannitol, a molecule of similar size. This difference appears to result from a lower lipid solubility rather than saturable [(14)C]ALA transport from brain to blood. The K(i) for [(14)C]ALA for uptake into the neonatal brain was 7-fold higher than in the adult. However, again, this was unaffected by increasing plasma ALA concentrations suggesting a diffusional process. In contrast, at the blood-CSF barrier, there was evidence of carrier-mediated [(14)C]ALA transport from blood to choroid plexus and blood to CSF. Both processes were inhibited by administration of non-radioactive ALA and probenecid. However, experiments in choroid plexus epithelial cell primary cultures indicated that transport in these cells was polarized with [(14)C]ALA uptake from the apical (CSF) side being about 7-fold greater than uptake from the basolateral (blood) side. In total, these results suggest that the brain is normally fairly well protected from changes in plasma ALA concentration by the very low blood-brain barrier permeability of this compound and by a saturable efflux mechanism present at the choroid plexus.

Aminolevulinic Acid↗
PubMed2003

Fluorescence-guided resections of malignant gliomas--an overview.

Radical resections of contrast-enhancing tumour in patients with malignant gliomas may be pertinent for survival but are often difficult to achieve due to uncertainties in distinguishing tumour margins intra-operatively. In this respect a number of novel methods are being examined which aim at enhancing resections. Among these methods, resections that exploit the accumulation of fluorescent porphyrins within malignant glioma tissue in response to exogenous administration of a metabolic percursor, 5-aminolevulinic acid, may offer particular advantages. This article summarises the clinical background and current status of 5-ALA drug development for fluorescence-guided resections of malignant gliomas and analyses the available literature with regard to possible mechanisms that govern the highly specific accumulation of fluorescent porphyrins in malignant glioma tissue in response to 5-ALA administration.

Aminolevulinic Acid↗
PubMed2002

Experimental research photodynamic effects in perifocal, oedematous brain tissue.

BACKGROUND: Photodynamic therapy (PDT) has been under discussion as additional treatment option for malignant gliomas. However, damage not only to tumour tissue but also to normal brain has been demonstrated. The mechanisms of this unwanted side effect have not yet been clearly identified. Spreading of photosensitiser with oedema after disruption of the blood-brain-barrier and potential sensitisation of normal tissue has been found previously. The present study investigates the time- and dose-dependency of normal tissue damage to photodynamic therapy using Photofrin II after disruption of the blood-brain-barrier. METHODS: Male wistar rats anaesthetised with chloral hydrate were subjected to focal, cerebral cold lesions. Simultaneously, Photofrin II (PFII) was injected (2,5 or 5 mg/kg b.w.). Laser irradiation (630 nm) was performed after 4 h, 12 h and 24 h with varying light doses. Control groups were subjected to focal cold lesion alone, cold lesion with laser irradiation, PFII followed by laser irradiation, or laser irradiation alone (n=6 all groups). 24 h later, brains were removed for assessment of necrosis in coronal sections. FINDINGS: Light dose had a significant impact on the extent of necrosis. Compared to control animals (lesion only: 0.84 +/- 0.2 mm2; lesion and irradiation alone: 0.7 +/- 0.3 mm2), the area of necrosis was increased to 2.8 +/- 0.5 (50 J/cm2), 3.5 +/- 1,1 (100 J/cm2) and 4.3 +/- 0.7 mm2 (200 J/cm2, 5 mg/kg b.w.; p<0.01). This effect was time-dependent. Maximal necrosis (6.3 +/- 1,6 mm2) was observed when brains were irradiated 12 h after PFII injection, with less necrosis occurring at 24 h (2.8 +/- 0.4 mm2, p<0.01). Reducing sensitiser dose to 2.5 mg/kg b.w. resulted in a reduction of necrosis (2.09 +/- 0.2 mm2, p<0.05). INTERPRETATIONS: Damage to oedematous tissue after photodynamic therapy using i.v. PFII and laser light at 630 nm depends on laser dose, sensitiser dose and the time point of laser irradiation. The time point of PDT should be considered to prevent unwanted tissue reactions. In the clinical setting however, defined damage to peritumoural tissue may be advantageous. This should be achievable by optimised timing and dosage of photodynamic therapy.

Animals↗
PubMed2001

Transorbital keyhole approach to anterior communicating artery aneurysms.

OBJECTIVE: The transorbital keyhole approach to anterior communicating artery aneurysms was developed as a minimally invasive method for safe control of the anterior communicating artery complex. This approach does not necessitate resection of the gyrus rectus. METHODS: The technique is described in detail. The transorbital keyhole approach provides more ventral access than the supraorbital approaches, and the anterior communicating artery complex can be controlled by splitting the basal aspect of the interhemispheric fissure. RESULTS: Since late 1998, the authors have used the transorbital keyhole approach routinely. During the initial experience with 33 patients, the only observed complication specific to this approach was transient diplopia in one patient. At follow-up examinations 2 to 15 months after surgery, the cosmetic results were favorable as compared with those of standard pterional craniotomy. CONCLUSION: We have designed a small, custom-tailored approach to the anterior communicating artery complex for routine use. The small orbitocranial approach is a step toward the ideal of purely extra-axial safe control of anterior communicating artery aneurysms. The orbitocranial keyhole approach seems to be substantially better than the craniotomy, although it requires additional effort and time.

Esthetics↗
PubMed2000

Thalamic astrocytomas: surgical anatomy and results of a pilot series using maximum microsurgical removal.

Deep-seated astrocytomas within the basal ganglia and the thalamus are considered unfavourable for microsurgical removal since the circumferential neighbourhood of critical structures limits radical resection. On closer assessment, the thalamus has a unique configuration within the basal ganglia. Its tetrahedric shape has 3 free surfaces and only the ventrolateral border is in contact with vital and critical functional structures, e.g. the subthalamic nuclei and the internal capsule. The purpose of the present study was to investigate the feasibility of maximum microsurgical removal in a series of intrinsic thalamic astrocytomas. 14 patients with intrathalamic astrocytomas grades I to 4 as diagnosed by previous stereotactic biopsy or intra-operative frozen section were selected for maximum microsurgical removal. The infratentorial supracerebellar approach from the contralateral side was used for 4 limited neoplasms of the pulvinar. For the other 10 larger and more extensive processes a parieto-occipital transventricular approach was chosen. Final histology gave the result of astrocytoma grade 1 or 2 in 4 patients, and of astrocytoma grade 3 or 4 in 10 patients. Postoperative MRI confirmed reduction of the tumor mass by 80 to 100% in 11 of 14 cases. Regional ancillary radiotherapy with 60 Gy was administered postoperatively for astrocytomas grades 3 and 4. Two patients operated on via the posterior transventricular approach had new postoperative partial hemianopia. Five of the 14 patients finally needed a ventriculo-peritoneal shunt. During the follow-up time of 6 to 52 months, tumor progression/recurrence was observed in 6 of the 10 high grade and none of the low grade neoplasms. The present pilot series demonstrates the feasibility of the microsurgical concept. Comparison with other treatment modalities, such as brachytherapy, requires future consideration.

Adolescent↗
PubMed2000

Mechanisms of 5-aminolevulinic acid uptake at the choroid plexus.

5-Aminolevulinic acid (5-ALA) is a precursor of porphyrins and heme that has been implicated in the neuropsychiatric symptoms associated with porphyrias. It is also being used clinically to delineate malignant gliomas. The blood-CSF barrier may be an important interface for 5-ALA transport between blood and brain as in vivo studies have indicated 5-ALA is taken up by the choroid plexuses whereas the normal blood-brain barrier appears to be relatively impermeable. This study examines the mechanisms of 5-[(3)H]ALA uptake into isolated rat lateral ventricle choroid plexuses. Results suggest that there are two uptake mechanisms. The first was a Na(+)-independent uptake system that was pH dependent (being stimulated at low pH). Uptake was inhibited by the dipeptide Gly-Gly and by cefadroxil, an alpha-amino-containing cephalosporin. These properties are the same as the proton-dependent peptide transporters PEPT1 and PEPT2, which have recently been shown to transport 5-ALA in frog oocyte expression experiments. Choroid plexus uptake was not inhibited by captopril, a PEPT1 inhibitor, suggesting PEPT2-mediated uptake. The presence of PEPT2 and absence of PEPT1 in the choroid plexus were confirmed by western blotting. The second potential mechanism was both Na(+) and HCO(3)(-) dependent and appears to be an organic anion transporter, although it is possible that removal of Na(+) and HCO(3)(-) may indirectly affect PEPT2 by affecting intracellular pH. The presence of PEPT2 and a putative Na(+)/HCO(3)(-)-dependent organic anion transporter is important not only for an understanding of 5-ALA movement between blood and brain but also because these transporters may affect the distribution of a number of drugs between blood and CSF.

Aminolevulinic Acid↗
PubMed2000

Leukocyte-endothelium interactions in pial venules during the early and late reperfusion period after global cerebral ischemia in gerbils.

The contribution of leukocytes to secondary brain damage after cerebral ischemia is still under discussion. The purpose of the present study was to examine the pial microcirculation after global cerebral ischemia while focusing on leukocyte-endothelium interactions during the early and late reperfusion period of up to 4 days. A closed cranial window technique that leaves the dura mater intact was used. Global cerebral ischemia of 15 minutes' duration was induced in male Mongolian gerbils (n = 91). Pial microcirculation was observed by intravital fluorescence microscopy. Leukocyte-endothelium interactions (LEIs) in pial venules, vessel diameters, capillary density, and regional microvascular blood flow measured by laser Doppler flowmetry were quantified during 3 hours of reperfusion and in intervals up to 4 days after ischemia. Within 3 hours of reperfusion, the number of leukocytes (cells/100 microm x minute) rolling along or adhering to the venular endothelium increased from 0.1 +/- 0.2 to 28.4 +/- 17.4 (P < 0.01 vs. control) and from 0.2 +/- 0.2 to 4.0 +/- 3.8 (P < 0.05), respectively. There was no capillary plugging by leukocytes; capillary density remained unchanged. In the late reperfusion period, at 7 hours after ischemia, LEIs had returned to baseline values. Furthermore, from 12 hours to 4 days after ischemia, no LEIs were observed. Changes in regional microvascular blood flow did not correlate with LEIs. Global cerebral ischemia of 15 minutes' duration induces transient LEIs that reach a maximum within 3 hours of reperfusion and return to baseline at 7 hours after ischemia. LEIs are not related to changes in microvascular perfusion, which suggests mainly that the expression of adhesion receptors is necessary to induce LEIs rather than rheologic factors. It seems unlikely that this short-lasting activation of leukocytes can play a role in the development of secondary brain damage.

Animals↗
PubMed2000

The influence of cranioplasty on postural blood flow regulation, cerebrovascular reserve capacity, and cerebral glucose metabolism.

The indications for cranioplasty after decompressive craniectomy are cosmetic repair and, mainly, restoration of cerebral protection. Although neurological improvement after cranioplasty is repeatedly noted, the reasons for this still remain unclear. Few observations concerning the impact of CSF hydrodynamic and/or atmospheric pressure were published during the last decades. Relevant data concerning the cerebrovascular reserve capacity and cerebral glucose metabolism before and after cranioplasty have been lacking until now. To gain further insight, the present study was undertaken to investigate the impact of cranioplasty on indices of cerebral blood flow regulation and metabolism. Thirteen patients in whom extensive craniectomies had been performed underwent a meticulous study of blood flow velocities in the middle cerebral artery (MCA) and extracranial internal carotid artery (ICA), as assessed by transcranial Doppler (TCD) ultrasonography during postural maneuvers (supine and sitting positions) and during stimulation with 1 g of acetazolamide for the interpretation of cerebrovascular reserve (CVR) capacity. Twelve patients underwent 18-fluorodesoxyglucose positron emission tomography. These measurements were made before and 7 days after cranioplasty. Cranioplasty improved preoperative differences in MCA blood flow velocities when comparing the injured with the noninjured hemisphere. Similarly, cranioplasty resolved decreases in extracranial ICA blood flow in the injured hemisphere that were induced by postural changes, which was a constant finding prior to this procedure. More strikingly, however, the CVR capacity, which was severely impaired in both hemispheres, significantly increased after the procedure. Metabolic deficits, which were observed in the injured as compared with the noninjured hemisphere, were found to improve after reimplantation of the skull bone flap. Cranioplasty appears to affect postural blood flow regulation, CVR capacity, and cerebral glucose metabolism markedly. Thus, early cranioplasty is warranted to facilitate rehabilitation in patients after decompressive craniectomy.

Adult↗
PubMed2000

Influence of cranioplasty on postural blood flow regulation, cerebrovascular reserve capacity, and cerebral glucose metabolism.

OBJECT: The indications for cranioplasty after decompressive craniectomy are cosmetic repair and, mainly, restoration of cerebral protection. Although neurological improvement after cranioplasty is repeatedly noted, the reasons for this remain unclear. Few observations concerning the impact of cerebrospinal fluid hydrodynamic and/or atmospheric pressure have been published during the last decades. Relevant data concerning the cerebrovascular reserve (CVR) capacity and cerebral glucose metabolism before and after cranioplasty have been lacking until now. To gain further insight, this study was undertaken to investigate the impact of cranioplasty on indices of cerebral blood flow regulation and metabolism. METHODS: Thirteen patients in whom extensive craniectomies had been performed underwent a meticulous study of blood flow velocities in the middle cerebral artery (MCA) and extracranial internal carotid artery (ICA), as assessed by transcranial Doppler ultrasonography during postural maneuvers (supine and sitting positions) and during stimulation with 1 g of acetazolamide for the interpretation of CVR capacity. Twelve patients underwent 18-fluorodeoxyglucose positron emission tomography. These measurements were obtained before and 7 days after cranioplasty. Cranioplasty improved preoperative differences in MCA blood flow velocities when comparing those in the injured with those in the uninjured hemisphere. Similarly, cranioplasty resolved decreases in extracranial ICA blood flow in the injured hemisphere that were induced by postural changes, which was a constant finding prior to this procedure. More strikingly, however, the CVR capacity, which was severely impaired in both hemispheres, increased significantly after the procedure. Metabolic deficits, which were observed in the injured hemisphere, were found to improve after reimplantation of the skull bone flap. CONCLUSIONS: Cranioplasty appears to affect postural blood flow regulation, CVR capacity, and cerebral glucose metabolism markedly. Thus, early cranioplasty is warranted to facilitate rehabilitation in patients after decompressive craniectomy.

Acetazolamide↗
PubMed2000

Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients.

OBJECT: It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection. In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department. METHODS: Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. Fluorescing tissue was removed whenever it was considered safely possible. Residual enhancement on early postoperative MR imaging was quantified and related to each patient's characteristics to determine which factors influenced resection. Survival was analyzed using the Kaplan-Meier method and multivariate analysis was performed in which the Karnofsky Performance Scale (KPS) score, residual fluorescence, patient age, and residual enhancement on MR images were considered. Intraoperatively, two fluorescence qualities were perceived: solid fluorescence generally reflected coalescent tumor, whereas vague fluorescence mostly corresponded to infiltrative tumor. Complete resection of contrast-enhancing tumor was accomplished in 33 patients (63%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 18 of the 19 remaining patients. Age, residual solid fluorescence, and absence of contrast enhancement in MR imaging were independent explanatory factors for survival, whereas the KPS score was significant only in univariate analysis. No perioperative deaths and one case of permanent morbidity were encountered. CONCLUSIONS: The observations in this study indicate the usefulness of 5-ALA-induced tumor fluorescence for guiding tumor resection. The completeness of resection, as determined intraoperatively from residual tissue fluorescence, was related to postoperative MR imaging findings and to survival in patients suffering from GBM.

Adult↗
PubMed1999

Blood-brain barrier glutamine transport during normoglycemic and hyperglycemic focal cerebral ischemia.

This study examines the effects of middle cerebral artery (MCA) occlusion in the rat on blood to brain glutamine transport, a potential marker of early endothelial cell dysfunction. It also examines whether the effects of ischemia on glutamine transport are exacerbated by hyperglycemia. In pentobarbital-anesthetized rats, 4 hours of MCA occlusion resulted in a marked decline in the influx rate constant for [14C]L-glutamine from 16.1+/-1.2 microL.g(-1).min(-1) in the contralateral hemisphere to 7.3+/-2.5 microL.g(-1).min(-1) in the ischemic core (P < 0.001). This reduction was even greater in xylazine-ketamine-anesthetized rats in which the influx decreased to 2.6+/-1.1 microL.g(-1) min(-1). This greater reduction appears related to the hyperglycemia induced by xylazine-ketamine anesthesia. Glucose injection in pentobarbital-anesthetized rats also resulted in a greater decline in [14C]L-glutamine influx in the ischemic core but had no effect on the contralateral tissue. The effects of hyperglycemia on glutamine transport in the ischemic tissue were associated with a decline in plasma volume, which may reflect either endothelial cell swelling or plugging of the microvasculature. The reduction in glutamine transport during ischemia was progressive, but even as early as 1 hour, there was a 60% and 40% decline in influx in hyperglycemic and normoglycemic rats, respectively. The fall in [14C]L-glutamine influx may reflect a dissipation of the endothelial cell [Na+] gradient. A decline in this gradient would affect many blood-brain barrier transporters with potentially deleterious effects on the ischemic brain.

Animals↗
PubMed1999

Inducible nitric oxide synthase: a possible key factor in the pathogenesis of chronic vasospasm after experimental subarachnoid hemorrhage.

OBJECT: The role of nitric oxide (NO) in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH) is not well understood. Nitric oxide is a well-established vasodilatory substance; however, in SAH, NO may become a major source for the production of injurious free-radical species, leading to chronic cerebral vasospasm. Reactive overproduction of NO to counteract vascular narrowing might potentiate the detrimental effects of NO. The focus of the present study is to determine the extent of reactive induction of inducible nitric oxide synthase (iNOS) after experimental SAH. METHODS: Chronic vasospasm was induced in male Wistar rats by an injection of autologous blood (100 microl) into the cisterna magna followed by a second injection 24 hours later. A control group of 10 animals was treated with injections of 0.9% sodium chloride solution. Vasospasm was verified by pressure-controlled angiography after retrograde cannulation of the external carotid artery 7 days later. In 11 of 15 animals radiographic evidence of cerebral vasospasm was seen. The animals were perfusion fixed and their brains were removed for immunohistochemical assessment. With the aid of a microscope, staining for iNOS was quantified in 40-microm floating coronal sections. Immunohistochemical staining for iNOS was markedly more intense in animals with significant angiographic evidence of vasospasm. Virtually no staining was observed in control animals. Seven days after the second experimental SAH, labeling of iNOS was found in endothelial cells, in vascular smooth-muscle cells, and, above all, in adventitial cells. Some immunohistochemical staining of iNOS was observed in rod cells (activated microglia), in glial networks, and in neurons. CONCLUSIONS: The present study demonstrates induction of iNOS after experimental SAH.

Animals↗