Biomedical subjects

E Uhl

Publications and source records attributed to E Uhl.

At least 37 records · Page 2Linked to original sources

PubMed2001

Retinoic acid prevents experimental Cushing syndrome.

Cushing syndrome is caused by an excess of adrenocorticotropic hormone (ACTH) production by neuroendocrine tumors, which subsequently results in chronic glucocorticoid excess. We found that retinoic acid inhibits the transcriptional activity of AP-1 and the orphan receptors Nur77 and Nurr1 in ACTH-secreting tumor cells. Retinoic acid treatment resulted in reduced pro-opiomelanocortin transcription and ACTH production. ACTH inhibition was also observed in human pituitary ACTH-secreting tumor cells and a small-cell lung cancer cell line, but not in normal cells. This correlated with the expression of the orphan receptor COUP-TFI, which was found in normal corticotrophs but not in pituitary Cushing tumors. COUP-TFI expression in ACTH-secreting tumor cells blocked retinoic acid action. Retinoic acid also inhibited cell proliferation and, after prolonged treatment, increased caspase-3 activity and induced cell death in ACTH-secreting cells. In adrenal cortex cells, retinoic acid inhibited corticosterone production and cell proliferation. The antiproliferative action and the inhibition of ACTH and corticosterone produced by retinoic acid were confirmed in vivo in experimental ACTH-secreting tumors in nude mice. Thus, we conclude that the effects of retinoic acid combine in vivo to reverse the endocrine alterations and symptoms observed in experimental Cushing syndrome.

Adrenocorticotropic Hormone↗

PubMed2000

[When the computer is assisting the surgeon... Navigation systems will also find small brain metastases].

Intra-operative localization systems are increasingly being used in cranial and spinal surgery as orientation aids for the surgeon. The latest of these systems operates without the need for a mechanical or an electrical link between the surgical wound and the computer workstation in the operating room. Since both emission and detection of infrared light are handled by a special camera system, the use of such aids means maximum flexibility for the surgeon. Thus, in contrast to conventional systems, no additional electric cables or mechanical devices that may interfere with the surgeon's freedom of movement, are present. This overview article provides a short description of the technology, and discusses the experience gained with, and the results obtained in, 142 cranial and spinal neurosurgical procedures performed with the aid of the new neuro-navigation system.

Brain Neoplasms↗

PubMed2000

Intracranial hypertension influences the resolution of vasogenic brain edema following intracerebral hemorrhage.

Aim of the current study was to investigate the influence of intracranial hypertension on the resolution of vasogenic brain edema following intracerebral hemorrhage. An intracerebral hematoma was induced by 500 microliters of blood injected into the left frontal lobe of rabbits (n = 25). Na(+)-fluorescein (MW376) and Texas-Red-albumin (MW67.000) were administered intravenously as edema markers. By using a closed cranial window for superfusion of the brain surface and a ventriculo-cisternal perfusion the clearance of both fluorescence markers was measured in the CSF-effluates up to 8 hours using spectrophotometry. ICP was adjusted between 2-6 mmHg (low pressure, n = 10), 8-12 mmHg (moderate pressure, n = 10) or 14-20 mmHg (high pressure, n = 5). In all groups Na(+)-fluorescein started to accumulate at 60 min after induction of the hematoma in the subarachnoid space, while at 90 min in the ventricular system. In the low intracranial pressure group Na(+)-fluorescein (mean +/- SEM) in the ventricular system amounted to 1.47 +/- 0.42 nmol as compared to 1.34 +/- 0.41 nmol in the moderate, or 0.38 +/- 0.11 nmol in the high intracranial pressure group. In the subarachnoid space the marker reached 1.96 +/- 0.57 nmol, 4.15 +/- 1.28 nmol, or 0.96 +/- 0.32 nmol, respectively. In conclusion, the data demonstrate that vasogenic edema induced by an intracerebral hematoma is cleared into both CSF compartments, albeit with delay into the ventricular system. Edema resorption occurred earlier and to a higher extent into the subarachnoid space as compared to the ventricular system. Further, edema resorption is influenced by the actual intracranial pressure, with marked inhibition by a high intracranial pressure.

Animals↗

PubMed2000

Influence of the bradykinin B1/B2-receptor-antagonist B 9430 on the cerebral microcirculation and outcome of gerbils from global cerebral ischemia.

The influence of the bradykinin B1/B2 antagonist B 9430 on the cerebral microcirculation following global cerebral ischemia was investigated in a closed cranial window preparation in Mongolian gerbils by intravital fluorescence microscopy. Global cerebral ischemia (GCI) was induced by occlusion of both common carotid arteries for 15 min. Leukocyte-endothelium interactions, vessel diameters, and the segmental microvascular blood flow were observed by intravital microscopy before and up to three hours after global cerebral ischemia. Following the early reperfusion period the animals survived up to 4 days after ischemia. The neurological deficit and the body weight were assessed daily. On day 4 animals were subjected to perfusion fixation and the brain was removed. Nerve cell damage from ischemia was quantified histologically in cortex, hippocampus, and striatum. Animals with treatment received the bradykinin B1/B2 receptor antagonist B 9430 before (i.v.), during, and after ischemia (s.c.) until the end of the experiment. The frequency of leukocytes (cells/100 microns x min) rolling along the venular endothelium post ischemia was significantly decreased (p < 0.05) in treated animals as compared to untreated controls (33.0 +/- 6.2 vs. 8.5 +/- 2.3) as well as the number of leukocytes attached to the endothelial surface (7.2 +/- 3.0 vs. 2.0 +/- 1.0, n.s.). The neuroscore on day 4 (pre-ischemic control: 22 points) was reduced to 13.4 +/- 3.2 in untreated animals, while to 4.7 +/- 3.2 points in the treatment group. No differences between animals with and without treatment were found as to the number of viable neurons. Although bradykinin is released in the brain during global cerebral ischemia, its antagonisation does not improve outcome despite the effective inhibition of leukocyte-endothelium interactions.

Animals↗

PubMed2000

Acceleration of wound healing by topical drug delivery via liposomes.

BACKGROUND: Despite intensive research, impaired wound healing remains a considerable complication. Therefore, topically applied liposome-encapsulated buflomedil hydrochloride was investigated for its ability to improve wound repair in normal (n=16) and ischemic (n=16) skin tissue. METHODS: Experiments were performed using the wound healing model of the ear of hairless mice. Standardized skin wounds (4.25 mm(2)) were created by circular excision of the epidermal layer and the subcutaneous tissue. Liposomes were applied daily until complete neovascularization of the wound occurred. Tissue regeneration by complete epithelialization and neovascularization of the wound area, microcirculatory parameters, and leukocyte-endothelium interaction were investigated by means of intravital microscopy. Microvascular perfusion was assessed by laser-Doppler flowmetry. RESULTS: Topical application of buflomedil liposomes led to a significantly (P<0.05) accelerated wound closure in both normal (9.6+/-0.7 days) and ischemic (13.4+/-0.1 days) skin tissue compared with animals that were treated with unloaded liposomes (controls; 13.1+/-0.8 days; 15.3+/-0.6 days). Complete neovascularization of the wound was also enhanced (P<0.05) in buflomedil-treated animals (normal tissue 18.8+/-0.4 days; ischemic tissue 19.6+/-0.7 days) compared with controls (20.6+/-0.6 days; 22. 6+/-1.2 days). CONCLUSION: These data suggest that buflomedil-loaded liposomes might be of beneficial use for clinical wound care.

Administration, Cutaneous↗

PubMed2000

Accuracy and clinical applicability of a passive marker based frameless neuronavigation system.

A passive marker system permits the inclusion of an unlimited number of instruments and other devices during frameless stereotaxy. The aim of this study was to evaluate the accuracy and clinical applicability of a passive marker based frameless image guided system (VectorVision; BrainLab, Heimstetten, Germany) developed for surgical planning and intraoperative image guidance. The system was first applied to a plastic phantom to determine the accuracy of the system by measuring the difference between the actual probe position and its analogous position on the monitor screen. The navigational device was subsequently applied to 40 procedures for brain tumours and cavernomas. The mean error value between the image on the monitor screen and the real location in the phantom and the clinical study was 1.45 mm (+/-0.99) and 4.05 mm (+/-3.62), respectively. Many different instruments could be employed as pointing devices. It was helpful in minimising the size of the craniotomy. An average lengthening of the surgical procedure of 20 minutes was experienced. The neuronavigation system proved to be a useful surgical tool to approach and detect lesions larger than 5 mm in diameter. The passive marker technology is intuitive and enables the surgeon to use his or her own instruments at any time as a pointing device, thus avoiding further costs for specially designed surgical equipment.

Adult↗

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↗

PubMed1999

Technical note: a new model for quantitative analysis of brain oedema resolution into the ventricles and the subarachnoid space.

OBJECTIVE: The aim of the current study was to develop an experimental animal model for quantitative analysis of oedema resolution via the subarachnoid space and the ventricular system using fluorescent oedema markers. METHODS: Artificial cerebrospinal fluid (CSF) containing TRITC-albumin (MW 67.000D) and Na(+)-fluorescein (MW 376D) was continuously infused into the white matter of the left frontal lobe of New Zealand white rabbits (n = 6) at a rate of 100 microliters/h for 3 hrs. A closed cranial window for superfusion of the brain surface with artificial CSF fluid (3 ml/h) was implanted above the left parietal cortex for measurement of the fluorescence markers in the subarachnoid space. Uptake of the fluorescence indicators into the ventricles was quantified by ventriculo-cisternal perfusion (3 ml/h). The effluates were collected at 30 min intervals for 3 hrs after the start of infusion. Clearance of the oedema fluid into the perfusates was measured by fluorescence spectrophotometry. RESULTS: At an intracranial pressure of 15.0 +/- 1.7 mm Hg (mean +/- SEM) both indicators started to accumulate in the subarachnoid and ventricular perfusates at 90 min following onset of oedema fluid infusion. The concentrations of the indicators in the ventricular system increased to 7.7 +/- 5.1% of Na(+)-fluorescein and 16.1 +/- 13.0% of TRITC-albumin of the total amount infused were recovered in the ventricular system at 3 hours after start of the oedema infusion, while 3.4 +/- 3.2% of Na(+)-fluorescein and 3.7% +/- 3.2 of TRITC-albumin, respectively, were found in the effluates of the subarachnoid space. CONCLUSION: The present study demonstrates that resolution of vasogenic brain oedema into the cerebral ventricular system and the subarachnoid space following its entry into cerebral white matter can be quantitatively analysed using fluorescence markers, which serve as oedema fluid indicators. The results indicate that the oedema fluid is cleared not only into the ventricular system but also via the subarachnoid space.

Animals↗

PubMed1999

Retinoic acid stimulates meningioma cell adhesion to the extracellular matrix and inhibits invasion.

Meningiomas are tumours derived from the arachnoid and pia mater. During embryogenesis, these membranes develop from the migrating craniofacial neural crest. We have previously demonstrated that meningiomas have characteristic features of embryonic meninges. Craniofacial neural crest derivatives are affected during normal development and migration by retinoic acid. We speculated, therefore, that meningioma cell migration and invasion would be affected in a similar way. In this study we investigated the mechanisms of invasion and migration in meningiomas and the effects of retinoic acid (RA). We found that low doses of RA inhibit in vitro invasion in meningioma cells, without affecting cell proliferation or viability. The matrix metalloproteinases MMP-2 (72 kDa gelatinase) and MMP-9 (92 kDa gelatinase), which play a key role in invasion in other tumours, are not affected by RA. RA inhibits cell migration on collagen I and fibronectin. A possible mechanism for these effects is provided by the fact that RA strongly stimulates adhesion of meningioma cells to extracellular matrix substrates. As in vitro invasion, migration and decreased adhesion to the extracellular matrix correlate with the clinical manifestation of tumour invasion, we conclude that RA induces a non-invasive phenotype in meningioma cells.

Cell Adhesion↗

PubMed1999

Influence of platelet-activating factor on cerebral microcirculation in rats: part 1. Systemic application.

BACKGROUND AND PURPOSE: Platelet-activating factor (PAF) has been demonstrated to have a mediator function in shock, with some of its deleterious effects being attributed to its influence on microcirculation. Systemic PAF concentrations as found in shock could also compromise the cerebral microcirculation. Our purpose in the present study was to examine the influence of systemically applied PAF on microvascular perfusion and leukocyte-endothelium interactions in cerebral microvessels. METHODS: A closed cranial window technique was used for intravital fluorescence microscopy of the brain surface. PAF was infused in concentrations of 10(-12), 10(-9), and 10(-6) mol/L into the carotid artery (5 mL/h for 20 min) of Sprague-Dawley rats (n=30). The selective PAF receptor antagonist WEB 2170BS (2 mg/kg body weight) was used to inhibit specific PAF effects. RESULTS: The number of leukocytes (cells/100 microm. min) rolling along or adhering at the venular endothelium increased following infusion of PAF 10(-6) mol/L from 7.7+/-2.5 to 24.4+/-8.9 (P<0.05) and from 1.9+/-0.5 to 6.9+/-2.2 (P<0.05), respectively, within 2 hours. Mean arterial pressure decreased from 92+/-22 mm Hg to 49+/-17 mm Hg (P<0.05). The lower concentrations of PAF were less effective to decrease mean arterial pressure but also induced leukocyte-endothelium interactions. The intravenous administration of WEB 2170BS 15 min before the infusion of PAF 10(-6) mol/L prevented both systemic hypotension and activation of leukocyte-endothelium interactions. CONCLUSIONS: Increased systemic blood levels of PAF as found during shock can not only cause systemic arterial hypotension but also induce leukocyte-endothelium interactions in cerebral venules. The activation of leukocytes was found to be independent of PAF-induced arterial hypotension. The specificity of these results is confirmed by the findings that WEB 2170BS could inhibit the PAF-induced systemic hypotension as well as the activation of leukocytes.

Animals↗

PubMed1999

Influence of platelet-activating factor on cerebral microcirculation in rats: part 2. Local application.

BACKGROUND AND PURPOSE: Platelet-activating factor (PAF) is involved in the development of secondary brain damage after ischemic and traumatic brain injury. On the basis of data from studies in peripheral organs, we hypothesized that PAF-mediated effects after cerebral injury could be secondary to alterations in cerebral microcirculation. METHODS: Changes in cerebral microcirculation focusing on leukocyte-endothelium interactions were quantified with the use of a closed cranial window model in Sprague-Dawley rats (n=33) by means of intravital fluorescence microscopy. The brain surface was superfused with PAF in concentrations from 10(-3) (n=3) to 10(-12) mol/L (n=6) for 20 minutes (5 mL/h). RESULTS: PAF 10(-4) mol/L (n=4) increased the number of rolling and adherent leukocytes in venules from 9.7+/-0.4 to 19.7+/-2.3 cells/100 mm. min (P=NS versus control) and from 2.2+/-0.5 to 4.3+/-0.7 cells/100 mm. min (P<0.05 versus control), respectively. Lower concentrations did not elicit leukocyte-endothelium interactions. Vessel diameters remained unchanged except for a transient increase of arteriolar diameters during superfusion with PAF 10(-4) and 10(-6) mol/L (n=6). Although only a limited area of the brain surface was exposed to PAF, the mediator induced a significant dose-dependent transitory arterial hypotension and caused irreversible circulatory shock at the high concentration (PAF 10(-3) mol/L). Arterial hypotension after administration of PAF 10(-3) mol/L could be attenuated by the intravenous pretreatment with the PAF antagonist WEB 2170BS. CONCLUSIONS: PAF, when locally released after brain injury, can penetrate the blood-brain barrier and induce systemic effects, including arterial hypotension. Its role as a mediator in the development of secondary brain damage seems, at least in the initial phase, not to be associated with disturbances of cerebral microcirculation or activation of leukocytes.

Animals↗

PubMed1999

Evaluation of abstracts submitted for the annual meeting of the German Neurosurgical Society 1999--unravelling a mystery.

The evaluation for the abstracts submitted for the annual meeting of the German Neurosurgical Society together with the Swiss Neurosurgical Society in Munich 1999, is presented as it has developed during the meetings of the last years. 597 abstracts were reviewed by the 30 members of the review committee according to a 5 point grading system. Cut off for acceptance was a mean grading of 2.7 points. Abstracts better than 2.4 were accepted, abstracts worse than 2.7 were rejected. Experimental studies were judged slightly better than clinical studies: the mean grading of clinical and experimental studies was 2.55 +/- 0.5 vs. 2.72 +/- 0.6 (p < 0.02). All abstracts with a mean grading of 2.4-2.7 and a standard deviation > 1.0 were discussed in a meeting of the review committee. 353 abstracts were accepted. Some of the abstracts submitted for oral presentation had to be converted to poster presentations. Among others the decision was based on the grading of the abstract.

Abstracting and Indexing↗

PubMed1998

Resolution of experimental vasogenic brain edema at different intracranial pressures.

Resolution of vasogenic brain edema was examined using the infusion edema model in rabbits. Texas Red-albumin (MW 66,000 D) and sodium fluorescein (MW 376 D) dissolved in artificial cerebrospinal fluid (aCSF) were infused into the white matter of the left frontal lobe of the brain. To quantify the edema fluid cleared by the ventricular system, ventriculo-cisternal perfusion was performed with aCSF. A closed cranial window, implanted above the left parietal brain, served for studying resolution of the artificial edema fluid via the subarachnoid space. CSF-samples were collected in 30 minutes-intervals and analysed with a spectrophotometer. Clearance of edema fluid was examined under low (2-5 mm Hg), medium (9-12 mm Hg), or high (14-17 mm Hg) intracranial pressures (ICP). In the low pressure-group, both edema fluid markers were found in the ventriculo-cisternal and subarachnoid perfusate at 60 and 90 min, in the group with moderately increased ICP at 90 and 120 min, respectively. In the high ICP-group both fluorescence dyes appeared not less than 90 min in the ventricular system, while no increase at all could be found in the subarachnoid space. Our results imply that resolution of edema fluid via both the ventricular system and the subarachnoid space depends on the actual ICP level.

Animals↗

PubMed1998

Reduction of skin flap necrosis by transdermal application of buflomedil bound to liposomes.

The influence of the vasoactive drug buflomedil hydrochloride bound to liposomes (2 mg/ml) was investigated in an arterial pattern skin flap model using the ear of hairless mice. For flap creation, the ear is cut at four-fifths of its base, which leaves the anterior artery as the only feeding vessel of the flap. Liposomes were locally applied daily for 30 minutes up to 5 days after flap creation. Microvascular perfusion in the proximal, central, and distal parts of the flap was measured by laser Doppler flowmetry. The border between perfused and nonperfused tissue was visualized by intravital fluorescence microscopy using fluorescein isothiocyanate (FITC)-labeled dextran (Mr 150,000) for contrast enhancement of microvessels. The area of nonperfused tissue was assessed by digital planimetry. Five days after flap creation the nonperfused area amounted to 23.8 +/- 3.1 percent of total flap surface in treated ears compared with 46.1 +/- 5.6 percent in untreated ears (p < 0.05) of the contralateral side. Additional preoperative treatment for 5 days did not further reduce the area of nonperfused tissue (treated ears, 23.0 +/- 1.3 percent; control ears, 44.6 +/- 5.1 percent). Microvascular perfusion was higher in the postoperatively treated ears in all parts of the flap from day 1 after flap creation until termination of the experiment. Five days after flap creation, perfusion as measured by laser Doppler flowmetry was reduced to 46.0 +/- 10.8 percent in the distal part in control ears compared with 91.9 +/- 8.3 percent (p < 0.05) in treated animals. Additional preoperative treatment for 5 days did not result in further improvement. It is concluded that local application of the vasoactive drug buflomedil docked to liposomes could be of therapeutic use in the treatment of ischemic tissue, including skin flaps.

Animals↗

PubMed1998

Heterogeneous dopamine D2 receptor subtype messenger ribonucleic acid expression in clinically nonfunctioning pituitary adenomas.

Little is known about differences in the expression, localization, and function of the two dopamine D2 receptor subtypes, D2short and D2long (D2s and D2l), in either normal or adenomatous pituitary. We investigated the messenger RNA (mRNA) expression of the D2 receptor (D2R) subtypes in clinically nonfunctioning pituitary adenomas by in situ hybridization using subtype-specific oligonucleotides. The five normal pituitaries studied expressed similar ratios of D2R subtypes mRNA with a predominant expression of the D2l isoform. In 2 of 18 clinically inactive adenomas no D2R mRNA was found, whereas in 16 a heterogeneous expression of D2R isoforms was observed. Six adenomas expressed only the D2l and 2 adenomas only the D2s subtype mRNA; the remaining 8 expressed extremely varying proportions of the two subtypes. The D2R was found only in a subset of the nonfunctioning adenoma cells. In gonadotropin-immunopositive adenomas, the D2R was mainly localized in LH- and FSH-immunopositive cells. Probably because of the heterogeneous D2R subtype expression, suppression of cell proliferation was observed in only 3 of 9 adenoma cell cultures in which the growth inhibitory effect of bromocriptine was studied. Although there is some evidence that the presence of the D2s receptor subtype favors the growth inhibitory response to bromocriptine, further studies with a larger number of inactive adenomas are needed to confirm this speculation.

Adenoma↗

PubMed1997

The cross-sectional area of the cervical spinal canal in patients with cervical spondylotic myelopathy. Correlation of preoperative and postoperative area with clinical symptoms.

STUDY DESIGN: Retrospective analysis of routine computed tomography investigations. OBJECTIVE: To investigate whether the extent of clinical symptoms in patients undergoing surgery for cervical spinal myelopathy depends on the transsectional area of the cervical spinal canal. METHODS: Forty-five patients underwent surgery using different techniques to enlarge the width of the spinal canal. For clinical evaluation before and after surgery, a modified score of the Japanese Orthopedic Association was used (mean follow-up period, 19.6, 9.1 months). The cross-sectional area of the spinal canal in computed tomography scans (C4-C6) was quantified 1 day before and 1 week after surgery using pixel-dependent area calculation software for three different density ranges given in Hounsfield units. RESULTS: After surgery, a significant enlargement of the cervical spinal canal of 78.2 +/- 55.9% could be achieved. The Japanese Orthopedic Association score increased significantly by 3.7 +/- 2.2 points from a median preoperative score of 10 to a score of 14 after surgery. Patients with a preoperative Japanese Orthopedic Association score > or = 10 achieved a significantly better outcome after surgery. Conversely, no patient with a postoperative area larger than 1.6 cm2 achieved a score of less than 12 Japanese Orthopedic Association-points. No significant linear correlation, however, was found between the postoperative transsectional area and the postoperative Japanese Orthopedic Association score of all patients. CONCLUSION: The preoperative clinical presentation of the patient was found to be the only prognostic hint for improvement after surgery. Preoperative area measurements of the spinal canal cannot be used as a prognostic tool for surgical outcome. Further, the postoperative measurements do not correlate with the clinical outcome. These data, however, which refer to C4 to C6, provide evidence that every surgical procedure to enlarge the cervical spinal canal should result in an area of 1.6 cm or more.

Cervical Vertebrae↗

PubMed1997

Leukocyte-endothelium interactions in global cerebral ischemia.

A closed cranial window was implanted in male Mongolian Gerbils to investigate leukocyte-endothelium interactions (LEI) at the brain surface in global cerebral ischemia (GCI) by intravital fluorescence microscopy. Four days after 15 min of bilateral common carotid artery occlusion the ischemic tissue damage was histologically analysed in selectively vulnerable areas of the brain. The frequency of Rhodamine 6G labeled leukocytes rolling along ("roller") and firmly attached ("sticker") to postcapillary endothelium was assessed before and up to 180 min after GCI. As compared to the sham operated control animals induction of LEI was found in animals with GCI, following a steady increase up to a significant level attained at 60 min (rollers) or at 120 min of reperfusion (sticker), respectively (p < 0.05). In animals with cerebral ischemia histological assessment revealed a significant decrease of viable neurons in the CA1-sector of hippocampus (neurons/mm2 +/- SEM: 1308 +/- 71 vs. 829 +/- 106), in parietal neocortex (727 +/- 17 vs. 542 +/- 49), and in striatum (547 +/- 26 vs. 352 +/- 49; p < 0.01), respectively. A significant correlation between the extent of irreversible neuronal damage and the frequency of leukocyte adherence to the endothelium could not be established. Nevertheless a direct correlation between the number of surviving neurons and of rolling leukocytes was observed, which may be suggestive of a protective potential of leukocyte rolling.

Animals↗

PubMed1997

Quantitative analysis of brain edema resolution into the cerebral ventricles and subarachnoid space.

Resolution of vasogenic brain edema was examined using a model of infusion of fluid into the brain of rabbits. For this purpose infusion of Texas Red-albumin (MW 67.000 D) and sodium fluorescein (MW 376 D) dissolved in artificial cerebrospinal fluid (mock CSF) was made into the white matter of the left frontal lobe of the brain. In order to quantify the portion of edema fluid which was cleared by the ventricular system, a ventriculo-cisternal perfusion was performed with mock CSF. A closed cranial window was implanted above the left parietal brain for superfusion of the cerebral cortex with mock CSF, in order to study resolution of the artificial edema fluid via the subarachnoid space. CSF-samples were collected in 30 minutes-intervals and analysed with a spectrophotometer. The clearance of edema fluid was examined under low (2-5 mmHg) and medium (9-12 mmHg) intracranial pressure (ICP). In the low-pressure group both edema fluid markers were found in the ventriculo-cisternal and subarachnoid perfusate at 60 min and 90 min, respectively, after start of infusion. In the group with moderately increased ICP the markers appeared at 90 min and 120 min, respectively. The amount of clearance of fluorescent dye via the subarachnoid space was the same in both groups and independent of the intracranial pressure.

Animals↗