Biomedical subjects

T Brinker

Publications and source records attributed to T Brinker.

At least 19 recordsLinked to original sources

PubMed2002

The role of cerebral blood flow and cerebrovascular reserve capacity in the diagnosis of chronic hydrocephalus--a PET-study on 60 patients.

AIM: To investigate the clinical value of cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) in the management of chronic hydrocephalus. Global cortical CBF and CVR in 60 patients (66 +/- 12 yrs) with chronic hydrocephalus were investigated before, one week (7 d) and 7 months (7 m) after shunting by 15-O-H2O PET (Siemens ECAT 951/31) at rest and after application of acetazolamide (1 g). After 7 months, clinical outcome was assessed according to Stein and Langfitt and patients were classified into responder (n = 31) and non-responder (n = 29). Before Surgery, responder had lower blood flow values compared to non responder (36 +/- 8 vs. 41 +/- 11 ml/100 ml/min; p = 0.04), whereas CVR was not different between outcome groups (33 +/- 10 vs. 41 +/- 8%; p > 0.05). After shunting, CVR in non-responder decreased from 41 +/- 8% to 32 +/- 5% (7 d), whereas in responder significant increases (p < 0.02) to 55 +/- 46% (7 d) and 54 +/- 31% (7 m) were observed. Regarding early individual changes in CVR, the majority (12/18; 66%) of non-responder had marked decreases in CVR-levels (< 30%), whereas clinical responder considerably improved in CVR (> 30%) in half of patients (7/14). Measurement of cerebral blood flow in chronic hydrocephalus might substantially contribute to selection of shunt candidates and neurological sequels may be rather related to early regeneration of the hemodynamic reserve.

Acetazolamide↗

PubMed2002

PET-studies in idiopathic chronic hydrocephalus before and after shunt-treatment: the role of risk factors for cerebrovascular disease (CVD) on cerebral hemodynamics.

AIM: To investigate the impact of cerebrovascular risk factors in idiopathic chronic hydrocephalus concerning cerebral hemodynamics and clinical outcome after shunting. Global cortical cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) in 53 patients (67 +/- 11 yrs) were determined by 15-0-water-PET studies before and after administration of acetazolamide (1 g) prior (pre), one week (7 d) and seven months (7 m) after shunting. According to the prevalence of vascular risk factors (American subcommittee on reporting standards for cerebrovascular disease) patients were classified into a "low-risk" (n = 27) and "high-risk" (n = 20) group; patients with a history of stroke (n = 6) were separated. After 7 months, clinical outcome was assessed according to Stein and Langfitt. While CBF in "high-risk" patients prior to surgery was significantly lower in clinical responder compared to non-responder (32 +/- 5 vs. 42 +/- 15 ml/100 ml/min; p < 0.05), CVR was marginal in both outcome groups (< 30%). One week after shunting, CVR in responder of "high-risk" significantly increased (64 +/- 30 vs. 31 +/- 10% pre; p < 0.01). In "low-risk" patients, differences in CVR prior to shunting were found: CVR was lower in clinical responder than in non-responder (36 +/- 11 vs. 47 +/- 22% pre; p > 0.05) and deteriorated in non-responder (29 +/- 15% vs. 47 +/- 22 pre; p < 0.02) one week after shunting. Different peri-operative characteristics in global CVR regarding clinical response after shunting between both "risk-groups" were observed. Pathophysiological mechanisms upon clinical sequels after shunting in idiopathic hydrocephalus may not be unique.

Cerebrospinal Fluid Shunts↗

PubMed2002

Regional cerebral blood flow profiles of shunt-responder in idiopathic chronic hydrocephalus--a 15-O-water PET-study.

AIM: To find out if regional characteristics of cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) may indicate shunt response in idiopathic chronic hydrocephalus. 11 patients with idiopathic chronic hydrocephalus (65 +/- 13 yrs) were followed-up within a year after shunting. Patients were classified into clinical responder (n = 5) and non-responder (n = 6) according to Stein and Langfitt. All patients had measurement of CBF and CVR with dynamic 15-O-water PET (Siemens ECAT 951/31) before and after application of acetazolamide (1 g). Regional differences between outcome groups were analysed with "statistical Parametric Mapping" (SPM99b; Wellcome Department, London, UK). Group differences were regarded as significant, when uncorrected p-value on voxel and on cluster level were p < 0.001 and p < 0.05, respectively. Regarding CBF distribution there was significantly reduced CBF in the frontobasal cortex in responder compared to non-responder (cluster level p = 0.026). In CVR, a variety of cortical regions showed significant decreases compared with non-responder: also in frontobasal cortex (on cluster level p = 0.009). However, most significant reductions were found in temporodorsal and limbic cortical regions (on cluster level p < 0.001). Preoperative hemodynamics displayed a regional profile of reduced CBF and CVR in patients with shunt improvement. Prospective studies for determining the accuracy of regional blood flow characteristics for outcome prediction are warranted.

Aged↗

PubMed2002

Neuropsychological testing to improve surgical management of patients with chronic hydrocephalus after shunt treatment.

AIM: To find out a practical neuropsychological tool for early and reliable outcome assessment in chronic hydrocephalus. In 30 patients (65 +/- 13 yrs.) 11 neuropsychological tests providing a wide range of psychomotor functions (visual and verbal attention, verbal memory and learning and visuomotor skills) were applied before (pre), one week (early) and 7 months (late) after shunting. After 7 months, clinical outcome was classified according to Stein and Langfitt. Statistics included factor analysis, logistic regression and non-parametric tests. Visual attention ("Digit-symbol"), verbal recall ("10-words-list") and motor precision ("line-tracing") were the most representative (and practical) tests (orthogonal loads > 0.9). These tests, in contrast to others, revealed significant differences between outcome groups concerning early postoperative changes: responder showed marked improvement in visual attention t-scores (47 +/- 8 vs. 41 +/- 8 (pre); p = 0.005) and motor precision scores (109 +/- 26 vs. 149 +/- 47 (pre); p = 0.03). Non-responder even decreased in verbal recall t-scores early after shunting (35 +/- 7 vs. 41 +/- 11 (pre); p = 0.007). By logistic regression, visual attention was most sensitive indicating shunt-response by early psychometric changes (p = 0.04). Psychomotor deficits in hydrocephalic patients can be represented by a few neuropsychological skills: visual attention, verbal recall and line tracing. Since they showed early post-operative differences regarding long-term response to shunting they may offer a practical and standardised method for reliable follow-up.

Aged↗

PubMed2002

Neuropsychological sequels to changes in global cerebral blood flow and cerebrovascular reserve capacity after shunt treatment in chronic hydrocephalus--a quantitative PET-study.

AIM: To study relationship of neuropsychological deficits in chronic hydrocephalus before and after shunting with dynamics in cerebral blood flow. In 27 patients (65 +/- 13 yrs) with idiopathic chronic hydrocephalus 11 selected neuropsychological tests, providing a wide range of psychomotor functions, were performed before, one week (early) and 7 months (late) after shunting. Parallel global cortical blood flow (CBF) and cerebrovascular reserve capacity (CVR) were determined by dynamic 15-O-water PET studies (Siemens ECAT 951/31) before and after application of acetazolamide (1 g). Test raw data and changes after treatment were compared with global and regional blood flow values by polynomial regression. No relationship of test profiles with hemodynamics before surgery was found. After one week, improvement of gait was related to an increase in cerebrovascular reserve capacity (p = 0.05). After 7 months changes in mental tests were related to changes in hemodynamics: again increases in CVR were significantly related to improvements in visual attention and verbal memory (p < 0.01). Early improvement of hemodynamic reserve was related to improvement in gait, whereas mental improvement was particularly related to increases in global CVR at later periods after shunting. These results indicate that neurological sequels in idiopathic chronic hydrocephalus after shunting may actually depend on consecutive improvement of cerebral hemodynamics.

Aged↗

PubMed2002

Dynamic shunt testing applying short lasting pressure waves--inertia of shunt systems.

Laboratory shunt testing often comprises only static pressure flow and flow pressure tests. We applied shorter acting pressure waves using a computerised shunt testing rig to investigate shunt behaviour under conditions that might occur in the clinical situation, e.g. during nocturnal vasogenic pressure waves or shorter rises in ICP at movements or exercise. Additionally the influence of a human-like compliance situation compared to a fixed pressure/volume relationship was investigated. Shunts behaved very differently than seen in static tests and demonstrated a marked inertia the shorter pressure waves acted. Although some valves opened at higher pressure, all valves showed marked hysteresis and none did close--if at all--at the specified pressure level. This behaviour might be a cause of shunt overdrainage not related to siphoning. The simulation of a human-like variable pressure-volume relationship with higher compliance at lower pressures had a positive effect on shunt function by decreasing the amount of drained volume. We therefore suggest to include dynamic pressure wave testing if hydrodynamic properties of shunts are to be evaluated.

Cerebrospinal Fluid↗

PubMed2002

Long-time in-vivo metabolic monitoring following experimental brain contusion using proton magnetic resonance spectroscopy.

In a Sham-controlled study we applied proton magnetic resonance spectroscopy (1H-MRS) at 4.7 T to a model of experimental traumatic brain contusion. The time course of cerebral metabolite changes was monitored in serial investigation in 14 Sprague Dawley rats up to 4 weeks after trauma. 6 animals served as controls. 1H-MRS spectra were acquired from a voxel covering the hippocampus/basal ganglia ipsi and contralateral to the lesion. Metabolites ratios of the injured hemisphere were compared to those ipsilateral in Sham animals and to those of the contralateral side in the trauma animals. NAA/Cr ratio and Glu/Cr ratio, possible markers of neuronal loss, persistently decreased after trauma to a minimum of -40% and -20% versus controls, respectively. One week after trauma Cho/Cr ratio was strongly increased by 73%. This might indicate a high inflammatory activity at that time. Lac/Cr ratio showed long-lasting and continuing increases up to 2000% versus controls as a sign of permanently shifted posttraumatic energy metabolism. 1H-MRS proved to be a useful non-invasive method for in-vivo monitoring of posttraumatic metabolism also in models of brain contusion. In single cases however, accompanying haemorrhage can potentially prevent useful data acquisition.

Animals↗

PubMed2002

Determination of contusion and oedema volume by MRI corresponds to changes of brain water content following controlled cortical impact injury.

The time-course of brain contusion/oedema development as visualised by high-resolution MRI was compared to brain water content following experimental brain contusion. 36 Sprague-Dawley rats underwent Controlled Cortical Impact Injury (CCII), 24 served as controls. In 16 animals serial T2 weighted MRI investigations at 1 h, 4 h, 24 h and 7 d after CCII were performed, in 44 rats hemispheric brain water content was determined at the same time points by wet dry weight method. MRI lesion volume (mm3) and brain water content of injured hemisphere (%) showed for absolute and relative values a strictly parallel course. Significant posttraumatic increases had a maximum at 24 hours. Values on day 7 were below those of 1st h in both methods. The simple non-invasive MRI method quantifies contusion and surrounding penumbra according to elevated tissue water signal. The invasive wet dry weight method quantifies changes of hemispheric brain water content that are likely to take place in contusion core and surrounding penumbra. Therefore, from a theoretical aspect both methods seem comparable. Following experimental brain contusion, the simple MRI method might be an equally sufficient way to describe post-traumatic or post-therapeutic changes of lesion size and brain oedema.

Animals↗

PubMed2002

Traumatic subarachnoidal hemorrhage in the developing rat.

The aim of the present study was to utilize an experimental traumatic subarachnoidal hemorrhage model in the developing rat. Diffuse brain injury was produced in intubated and ventilated 21 to 25 days old Sprague-Dawley rats (N = 10) using a modification (1 m/100 g) of the Marmarou-model. Before induction of the injury heparin was administered i.v. and antagonised after injury by protamine. Mean arterial blood pressure and intracranial pressure was measured continuously. Histopathological investigations were performed. The results were compared to readings in adult animals (N = 12) subjected to a 1.5 m/500 g injury. In the developing rat ICP increased immediately following injury from 11.4 +/- 2.1 mm Hg to 55.9 +/- 20.3 mm Hg. It remained elevated till the end of the experiment 1 h after injury. MABP increased from 79.8 +/- 8.7 mm Hg to 100.2 +/- 21.7 mm Hg immediately following injury, returning to 61.3 +/- 28.7 mm Hg at the end of the experiment resulting in a marked decrease of CPP. The mortality rate was 60%. All brains showed a severe subarachnoidal hemorrhage in the basal cisterns. The increase of ICP following injury is attributable to the bleeding similar as in adult animals. The high mortality is due to the marked decrease of CPP. Rat pups are more vulnerable to t-SAH compared to adult rats.

Aging↗

PubMed2002

Spinal cerebrospinal fluid pathways and their significance for the compensation of kaolin-hydrocephalus.

AIM: To study the mechanisms of CSF-outflow in hydrocephalus we used radiological and histological methods to examine pathways of CSF absorption. Two, four and six weeks after occlusion of the cisterna magna by kaolin solution, CSF-dynamics were determined. Direct magnification radiography was used to visualize the outflow of X-ray contrast. Ten rats in each group were sacrificed for histological analysis following ventricular perfusion with marker proteins. ICP was increased to 15 +/- 1 mmHg (mean +/- SD) compared to control animals (7 +/- 2 mmHg) in the four week group. Six weeks following kaolin injection no increase in ICP (6 +/- 1 mmHg) could be demonstrated. Outflow resistance was markedly raised in all animals (1074 +/- 315 mmHg min-1 ml-1) displaying highest values (2160 +/- 960) in the four week group as compared to control animals (504 +/- 71). Cisternography demonstrated blocked cranial absorption and CSF-outflow along lumbosacral nerve roots. Histological examination showed syrinx formation in the cervical and thoracic spinal cord. Marker proteins left the subarachnoid space along thoracic and lumbo-sacral spinal rootlets. The radiological and histological findings and the normalisation of ICP after six weeks at doubled CSF-outflow resistance indicated a recruitment of spinal perineural CSF outflow pathways for the compensation of the disturbed cranial CSF-absorption.

Animals↗

PubMed2002

Temporal and regional profile of neuronal and glial cellular injury after induction of kaolin hydrocephalus.

AIM: To study regional and temporal pattern of glial and neuronal reaction to induction of kaolin hydrocephalus in adult rats. Enzyme- and immunohistochemistry was performed in 20 adult rats with kaolin-hydrocephalus after 2, 4, 6 and 8 weeks to glial glutamatergic transmission activity (GLDH) and neuronal nitrous oxide synthetic activity (nNOS). Also, glial fibrillary acidic protein (GFAP), 68 kd neurofilament protein (NF68) and synaptophysin (SYN38) and basic fibroblastic growth-factor (bFGF) were stained. Results were quantified by imaging analysis (SCION IMAGE) and expressed as relative immunopositive area. After 2 weeks, nNos-activity increased in cortical and hippocampal neurones (CA1 and CA3) and GLDH-activity also showed increases, most significant in periventricular white matter (25.7 +/- 3.8 vs. 15.5 +/- 4.9; p < 0.001) and hippocampus (p < 0.01). After 4 or 6 weeks, global cortical GLDH-activity showed further marked increases (25.7 +/- 3.9 vs. 11.3 +/- 1.5; p < 0.05), while sustained structural changes have occurred: GFAP decreased in periventricular (3.3 +/- 0.5 vs. 6.3 +/- 1.2; p < 0.01), hippocampal and cortical astrocytes (0.9 +/- 0.34 vs. 5.0 +/- 0.7%; p < 0.01), whereas NF68 in cortical efferent neurones increased (6.5 +/- 1.5% vs. 4.7 +/- 0.1; p < 0.01) followed by a decrease in cortical and hippocampal (CA1) SYN 38 (p < 0.05). Acute glial and neuronal reactions were almost functional and in chronic stages sustained structural changes predominated. Since neuronal reactions were pronounced in selective vulnerable areas glial reaction was not restricted to periventricular astrocytes.

Animals↗

PubMed2002

[Initial chronic results of flexible sieve electrodes as interface to nerve stumps].

Since more than 20 years, nerve stumps have been interfaced with sieve-like microsystems with integrated electrodes in experimental studies. In most cases, silicone tubes have been assembled on the microsystems to adapt the nerve and deliver a guidance structure for regeneration. Flexible, polyimide-based sieve electrodes with integrated fixation aids have been implanted chronically in an animal model. They have been adapted between the transsected ends of the sciatic nerve of rats and on the proximal stump in an amputation model. First electrophysiological experiments proved the functional reinnervation. Combining embryonic motor neurons with the sieve electrode, we propose a biohybrid system that is under investigation to functionally interface the distal part of a transsected peripheral nerve.

Animals↗

PubMed2001

Towards micro electrode implants: in vitro guidance of rat spinal cord neurites through polyimide sieves by Schwann cells.

Our goal is to develop biohybrid neural microprobe implants with sieve electrodes for external stimulation of co-implanted neurons whose axons penetrate through the holes of electrodes and innervate host targets such as denervated muscle fibers. For evaluation of implants, potential scar formation was imitated in fibroblast-spinal cord co-cultures. In vitro neurite extension through flexible 10-microm thick polyimide sieves was inhibited by co-cultured fibroblasts. In contrast, the neurite penetration of sieves could be greatly stimulated by oriented exposure to Schwann cells. To our knowledge this is the first direct proof that Schwann cells display a guidance effect on spinal cord neurons in vitro. The results pave the way for novel biohybrid neuro-implants and provide means to circumvent the obstacle of inhibitory scar formation.

Animals↗

PubMed2001

Regeneration of a transected peripheral nerve by transplantation of spinal cord encapsulated in a vein.

The objective was to investigate the regeneration of a transected peripheral nerve after transplantation of fragmented embryonic (E14-15) spinal cord cells which were encapsulated within a vein cavity. After 3 months transplantation, axonal regeneration was observed by staining with HE and antibody to neurofilament subtypes in six of 10 rats. In all six animals compound muscle action potentials to electrical stimulation could be recorded and indicated incomplete reinnervation of the fibular and tibial nerve, respectively. A chronic inflammation process around the transplant and a negative result of staining neurofilaments within the vein cavity and the transected nerve were found in animals lacking electrophysiological response to stimulation.

Action Potentials↗

PubMed2001

Chicken arachnoid granulations: a new model for cerebrospinal fluid absorption in man.

Cerebrospinal fluid (CSF) absorption was investigated chicken and rat using infusion tests into the cisterna magna. Data were analysed according to a mathematical model by Johnson et al. Results in rat predicted a predominant lymphatic mechanism, which was confirmed by rapid outflow of X-ray contrast media into the olfactoric mucosa. In contrast, dynamics measurements suggested CSF drainage via arachnoid granulations in chicken. CSF spaces along the optic nerve were contrasted radiographically resulting in venous drainage. Electron microscopically, villus-like structures were found at the distal optic nerve connecting the subarachnoid space with accompanying veins, resembling human arachnoid granulations. We hypothesize that CSF absorption through arachnoid villi in microsmatic chicken reflects the situation in man very well.

Animals↗

PubMed2001

Immunohistochemical characterization of axonal sprouting and reactive tissue changes after long-term implantation of a polyimide sieve electrode to the transected adult rat sciatic nerve.

The development of artificial microstructures suited for interfacing of peripheral nerves is not only relevant for basic neurophysiological research but also for future prosthetic approaches. Aim of the present study was to provide a detailed analysis of axonal sprouting and reactive tissue changes after implantation of a flexible sieve electrode to the proximal stump of the adult rat sciatic nerve. We report here that massive neurite growth after implantation, steadily increasing over a period of 11 months, was observed. Parallel to this increase was the expression of myelin markers like Po, whereas non-myelin-forming Schwann cells did not change. Compared to five weeks post-implantation. where both Schwann-cell phenotypes were intermingled with each other, non-myelin-forming Schwann cells occupied a peripheral position in each microfascicle after 11 months. After an initial increase, hematogenous macrophages were down-regulated in number but maintained close contact with the implant. However, at no time were signs of its degradation observed. It is concluded that the introduced flexible polyimide electrode is suitable for contacting peripheral nerves since it permits substantial neurite growth and offers excellent long-term stability.

Animals↗

PubMed2001

Far-field responses to stimulation of the cochlear nucleus by microsurgically placed penetrating and surface electrodes in the cat.

OBJECT: A new generation of penetrating electrodes for auditory brainstem implants is on the verge of being introduced into clinical practice. This study was designed to compare electrically evoked auditory brainstem responses (EABRs) to stimulation of the cochlear nucleus (CN) by microsurgically implanted surface electrodes and insertion electrodes (INSELs) with stimulation areas of identical size. METHODS: Via a lateral suboccipital approach, arrays of surface and penetrating microelectrodes with geometric stimulation areas measuring 4,417 microm2 (diameter 75 microm) were placed over and inserted into the CN in 10 adult cats. After recording the auditory brainstem response (ABR) at the mastoid process, the CN, and the level of the inferior colliculus, EABRs to stimulation of the CN were recorded using biphasic, charge-balanced stimuli with phase durations of 80 microsec, 160 microsec, and 240 microsec at a repetition rate of 22.3 Hz. Waveform, threshold, maximum amplitude, and the dynamic range of the responses were compared for surface and penetrating electrodes. The EABR waveforms that appeared for both types of stimulation resembled each other closely. The mean impedance was slightly lower (30 +/- 3.4 kohm compared with 31.7 +/- 4.5 kohm, at 10 kHz), but the mean EABR threshold was significantly higher (51.8 microA compared with 40.5 microA, t = 3.5, p = 0.002) for surface electrode arrays as opposed to penetrating electrode arrays. Due to lower saturation levels of the INSEL array, dynamic ranges were almost identical between the two types of stimulation. Sectioning of the eighth cranial nerve did not abolish EABRs. CONCLUSIONS: Microsurgical insertion of electrodes into the CN complex may be guided and monitored using techniques similar to those applied for implantation of surface electrodes. Lower thresholds and almost equivalent dynamic ranges indicate that a more direct access to secondary auditory neurons is achieved using penetrating electrodes.

Animals↗

PubMed2000

1H-MR spectroscopic monitoring of posttraumatic metabolism following controlled cortical impact injury: pilot study.

Proton magnetic resonance spectroscopy (1H-MRS) has been increasingly utilised in experimental traumatic brain injury for characterisation of posttraumatic metabolic dysfunction. Following human brain injury pathological findings correlated with outcome measures. Combined with conventional T2-weighted MR imaging MRS is a sensitive tool to evaluate metabolic changes in brain tissue following trauma. Studies have been restricted so far to diffuse axonal injury models and fluid percussion injury. Using a high resolution scanner at 4.7 T, MRI combined with 1H-MRS was applied in a pilot study to the controlled cortical impact injury model of experimental brain contusion (CCII). Eight Sprague-Dawley rats were investigated, of which two served as controls. Four animals were injured 24 h after craniotomy, two investigated at 72 h post craniotomy. MRS/MRI indicated a transient brain oedema development and metabolic changes induced by the craniotomy itself. Following CCII MRI demonstrated that the area of contusion as well as the surrounding brain oedema increased twofold in size within 24 h (p < 0.05). MRS showed an immediate increase of N-acetylaspartate (NAA) and glutamate ipsilateral to the contusion and a drop of NAA on the contralateral side. MRS/MRI investigations in the CCII model demonstrated a potential to further elucidate the pathophysiology following traumatic brain contusion.

Animals↗