Evaluation of three new models of hydrocephalus shunts.

OBJECTIVE: To assess the hydrodynamic properties of three new types of hydrocephalus valve. METHODS: Three new constructions have been recently tested in the UK shunt Evaluation Laboratory: the magnetically adjustable Strata Valve (Medtronic PS Medical), the gravitational Miethke Dual-Switch Valve (Aesculap) and the ventriculo-sinus SinuShunt (CSF Dynamics). Pressure-flow performance curves were assessed in a minimum of three samples of each valve to study their longterm variability, influence of temperature, negative outlet pressure, external pressure, presence of pressure pulsations, etc. RESULTS: The operating pressure of the Strata Valve can be adjusted magnetically in five steps. This Shunt prevents 'siphoning' but is sensitive to external pressure. The Dual Switch Miethke Valve is a system of two fixed-pressure ball-on-spring valves with a lower opening pressure operating in a horizontal body position and higher when vertical. This function is designed to cancel the effect of siphoning related to body posture. Both Strata and DSV valves have a low hydrodynamic resistance (less than 3 mm Hg/ml/min), and hence they cannot prevent overdrainage related to nocturnal vasomotor waves. The SinuShunt has a higher resistance (9 mm Hg/(ml/min)) and a lower opening pressure. The valve is intended to drain CSF from ventricles to the transverse sinus. CONCLUSION: New shunt technology continues to evolve. Laboratory evaluation independent of the manufacturer forms an important link between R&D laboratories and clinical practice.

A prospective study of discordance in diagnosis of osteoporosis using spine and proximal femur bone densitometry.

The T-score definition of osteoporosis, originally intended for epidemiologic research in this condition, is frequently used in making treatment decisions for individual patients. Discordance in classification depending on the site and type of measurement has been reported in retrospective and cross-sectional studies, but the impact of such discordance on clinical practice is unknown. This is potentially important in view of a recent proposal to confine osteoporosis diagnosis to densitometry at the hip. Having excluded those with degenerative changes in the lumbar spine, we compared the T-score classification of a prospective cohort of patients referred for their first dual-energy X-ray absorptiometry (DXA) scan, analyzing data for men and women in 10-year age groups. Total hip and neck of femur DXA identified significantly fewer osteoporotic patients than spine DXA, and this reduced sensitivity could not be improved by adjusting the T-score threshold without an unacceptable increase in non-osteoporotic cases. The majority of patients undetected by proximal femur DXA were at significantly increased risk of vertebral fracture. DXA at the lumbar spine had only moderate sensitivity and specificity for osteoporosis redefined by total hip densitometry, indicating differential rates of bone loss at the proximal femur and spine. We conclude that, as the most usual indication for bone densitometry is to aid the determination of an individual's fracture risk, both proximal femur and lumbar spine should continue to be assessed.

Laboratory testing of hydrocephalus shunts -- conclusion of the U.K. Shunt evaluation programme.

16 models of valves, currently in use in the U.K., have been tested long-term in the U.K. Shunt Evaluation Laboratory according to the protocol based on the new ISO 7197 standard. Valves tested were: Medtronic PS Medical: Delta Valve, Flow Control and Lumbo-Peritoneal Shunt, Heyer-Schulte Nero-Care: In-line, Low Profile and Pudenz Flushing Valve, Codman: Codman-Hakim Programmable, Hakim Precision, Accu-Flo, Holter, Uni-Shunt, and siphon-preventing device -- SiphonGuard, NMT: Orbis-Sigma Valve, Omni-Shunt and Hakim Valve, Sophysa: Sophy Programmable Valve, Radionics: Contour-Flex Valve. The majority of the valves had a non-physiologically low hydrodynamic resistance (with the exception of Orbis-Sigma, PS Lumbo-Peritoneal and Heyer-Schulte In-Line). This may result in overdrainage both related to posture and during nocturnal cerebral vasogenic waves. A long distal catheter increases the resistance of these valves by 100-200%. Drainage through valves without siphon-preventing mechanism is very sensitive to body posture. This may produce grossly negative intracranial pressure after implantation. A few shunts (Delta, Low Profile and Pudenz-Flushing with Anti-Siphon Devices) offer a reasonable resistance to negative outlet pressure, and hence potentially might prevent complications related to overdrainage. On the other hand, valves with siphon-preventing devices may be blocked by raised subcutaneous pressure (exception: SiphonGuard, but this device may block the drainage because of its faulty design). In most of the silicone-diaphragm valves, closing pressure varied and reached values lower than that specified by the manufacturer (exception: Heyer-Schulte Pudenz Flushing Valve). All programmable valves are susceptible to overdrainage in the upright body position. Programmed settings may be changed by external magnetic fields. Most shunts are very sensitive to the presence of small particles in the drained fluid. The behavior of a valve revealed during such testing is of immediate relevance to the surgeon and may not be adequately described in the manufacturer's product information. These results are also relevant to the assessment of shunt function in-vivo using an infusion test.

Uncoupling of cerebral blood flow and metabolism after cerebral contusion in the rat.

Positron emission tomography scans of patients with head injuries often show discrete areas of increased 18F-fluorodeoxyglucose uptake ("hot spots") when performed hours to days after the initial ictus. Using quantitative autoradiographic methods, the authors have investigated whether cerebral blood flow and glucose metabolism are uncoupled 2 hours after controlled head injury in an animal model, and whether any "hot spots" are accompanied by changes in cerebral glucose concentration. Experiments were performed on 18 anesthetized, ventilated (1.5% halothane in 2:1 nitrous oxide:oxygen) Sprague-Dawley rats weighing 300 to 330 g. A burr hole was made over the left parietal cortex, and all animals received a piston impact on the intact dura (2 mm in diameter, 2.0 m/sec, 2 mm in depth). All animals remained anesthetized and ventilated for a further 2 hours, after which quantitative autoradiography was used to determine either (1) local cerebral blood flow (LCBF) using 14C-iodoantipyrine, (2) local cerebral glucose utilization (LCGU) using 14C-deoxyglucose, or (3) local cerebral glucose content (LCGC) using 14C-methylglucose. Local CBF, LCGU, and LCGC were measured in five regions adjacent to the contusion, and values then were normalized on the contralateral cortex. Normalized LCBF, LCGU, or LCGC varied in parallel in ipsilateral cortex (no change) and in the ischemic core of the contusion (reduced). However, there were marked changes in the patterns observed in the boundary zone (within 1 mm of the contusion). In all six rats used for LCGU measurement, there were discrete areas of high metabolism, whereas in all six rats used for LCBF measurement, flow was universally depressed in the boundary zone. Of the six rats used for LCGC determination, there was a discrete area of high signal in only one. The authors conclude that there are discrete areas of uncoupling of cerebral blood flow and metabolism after head injury within 2 hours of cerebral contusion in the rat that cannot be explained by changes in cerebral glucose content in the majority of animals.

Laboratory evaluation of the phoenix CRx diamond valve.

OBJECTIVE: To assess the long-term hydrodynamic properties of a new cerebrospinal fluid flow-regulating hydrocephalus shunt called the CRx Diamond valve (Phoenix Biomedical Corp., Valley Forge, PA). METHODS: Three samples of a Diamond valve were tested in the United Kingdom Shunt Evaluation Laboratory during a 40-day period. Tests were performed for long-term pressure-flow performance, overdrainage, susceptibility to ambient temperature changes, external pressure, reflux, presence of small particles in the reagent, mechanical durability, and magnetic resonance imaging compatibility. RESULTS: Tests demonstrated that the Diamond valve stabilized flow within the range of 0.36 to 0.62 ml/min when pressure varied from 14 to 23 mm Hg. Hydrodynamic resistance demonstrated pressure-dependent variability from 20 to 78 mm Hg/(ml/min). The time drift of hydrodynamic parameters was significant (P < 0.001). The valve was insensitive to changes in temperature, external pressure, rapid fluctuations of differential pressure, small particles in fluid, and reflux. CONCLUSION: The Diamond valve demonstrated the intended variable resistance, which increased as the pressure increased. This property may help it limit overdrainage related to body posture as well as nocturnal vasogenic waves. Flow through the valve stabilizes within a wide range, which may contribute to the prevention of excessive pressure buildup after implantation. However, shunt placement should be avoided in patients who present with normal baseline intracranial pressure but an increased incidence of high vasogenic intracranial pressure waves.

Principles of quality management in medicine: the British concept.

The National Health Service in Great Britain is undergoing radical change particularly with regard to clinical governance, self-regulation, revalidation, career structures and training and patterns of healthcare delivery. All these changes are relevant to risk-control and quality management. This review surveys these generic changes and illustrates the implications for neurosurgery. Neurosurgery in the UK has the opportunity to enhance their patients care by expanding the number of consultants, developing further sub-specialisation and enhancing its training and review and dissemination programmes but only if extra resources are provided.

Cerebral venous blood outflow: a theoretical model based on laboratory simulation.

OBJECTIVE: The cerebrovascular bed and cerebrospinal fluid circulation have been modeled extensively except for the cerebral venous outflow, which is the object of this study. METHODS: A hydraulic experiment was designed for perfusion of a collapsible tube in a pressurized chamber to simulate the venous outflow from the cranial cavity. CONCEPT: The laboratory measurements demonstrate that the majority of change in venous flow can be attributed to either inflow pressure when the outflow is open, or the upstream transmural pressure when outflow is collapsed. On this basis, we propose a mathematical model for pressure distribution along the venous outflow pathway depending on cerebral blood flow and intracranial pressure. The model explains the physiological strong coupling between intracranial pressure and venous pressure in the bridging veins, and we discuss the limits of applicability of the Starling resistor formula to the venous flow rates. The model provides a complementary explanation for ventricular collapse and origin of subdural hematomas resulting from overshunting in hydrocephalus. The noncontinuous pressure flow characteristic of the venous outflow is pinpointed as a possible source of the spontaneous generation of intracranial slow waves. CONCLUSION: A new conceptual mathematical model can be used to explain the relationship between pressures and flow at the venous outflow from the cranium.

Clinical cerebral microdialysis: a methodological study.

OBJECT: Clinical microdialysis enables monitoring of the cerebral extracellular chemistry of neurosurgical patients. Introduction of the technique into different hospitals' neurosurgical units has resulted in variations in the method of application. There are several variables to be considered, including length of the catheter membrane, type of perfusion fluid, flow rate of perfusion fluid, and on-line compared with delayed analysis of samples. The objects of this study were as follows: 1) to determine the effects of varying catheter characteristics on substance concentration; 2) to determine the relative recovery and true extracellular concentration by varying the flow rate and extrapolating to zero flow; and 3) to compare substance concentration obtained using a bedside enzyme analyzer with that of off-line high-performance liquid chromatography (HPLC). METHODS: A specially designed bolt was used to conduct two adjacent microdialysis catheters into the frontal cortex of patients with head injury or poor-grade subarachnoid hemorrhage who were receiving ventilation. One reference catheter (10-mm membrane, perfused with Ringer's solution at 0.3 microl/minute) was constant for all studies. The other catheter was varied in terms of membrane length (10 mm or 30 mm), perfusion fluid (Ringer's solution or normal saline), and flow rate (0.1-1.5 microl/minute). The effect of freezing the samples on substance concentration was established by on-line analysis and then repeated analysis after storage at -70 degrees C for 3 months. Samples assayed with the bedside enzyme analyzer were reassessed using HPLC for the determination of glutamate concentrations. CONCLUSIONS: Two adjacent microdialysis catheters that were identical in membrane length, perfusion fluid, and flow rate showed equivalent results. Variations in perfusion fluid and freezing and thawing of samples did not result in differences in substance concentration. Catheter length had a significant impact on substance recovery. Variations in flow rate enabled the relative recovery to be calculated using a modification of the extrapolation-to-zero-flow method. The recovery was approximately 70% at 0.3 microl/minute and 30% at 1 microl/minute (10-mm membrane) for all analytes. Glutamate results obtained with the enzyme analyzer showed good correlation with those from HPLC.

A clinical audit of the Hakim programmable valve in patients with complex hydrocephalus.

The objective of the investigation was to determine the pattern of use of the Hakim (Medos) programmable valve implanted in patients with complex hydrocephalus and their clinical outcome. A prospective audit of patients with complex hydrocephalus undergoing Hakim programmable valve implantation between 1989 and 1994 in the United Kingdom and Ireland, was followed-up for a minimum of 5 years. Surgical practice and complications were audited together with clinical outcome. One-hundred-and-thirty-nine patients (80 male, 59 female; mean age 43.4 years; median 47 years; range 1 month-84 years) with complex hydrocephalus due to a wide range of aetiologies were implanted with the Hakim programmable valve. Eighty-eight (63%) had large or massive ventricles prior to implantation; seven (5%) were slit. Fifty-five (40%) had previously been shunted with a fixed pressure system. One-hundred-and-thirty-one (94%) of the Hakim programmable shunts were ventriculoperitoneal; four (3%) ventriculoatrial; two (1.4%) cystoperitoneal; and two (1.5%) lumboperitoneal. The initial opening pressure selected ranged from 50 to 200 mmH2O (median 120). Valves were reprogrammed on average 1.7 times with 143 reprogrammings in the first year after implantation; 67 in the second; 19 in the third; three in the fourth; two in the fifth. Forty-nine (36%) valves were never reprogrammed after implantation. During the 5 years audit period, there were 70 (50%) shunt revisions, 40 of which were performed within 1 year of implantation. Thirty-six (27%) shunts were removed. There were 24 (18%) shunt infections. Subdural collections were identified in 37(27%) patients after Hakim programmable valve implantation; 10 (27%) required surgical drainage. Five (3.7%) patients developed symptomatic slit ventricles after Hakim programmable valve implantation. Headache was improved following reprogramming in 27(71%) of the 38 patients with refractory headache. After Hakim programmable valve implantation, patients underwent an average of 4.6 CT scans (range 1-25); 0.3 MRI (range 1-5) and 1.8 skull radiographs (range 1-20). The mean hospital stay per patient over 5 years was 26 days (range 1-110 days). Five years after implantation, the Glasgow Outcome scale was favourable in 64% of patients. The Hakim programmable valve is useful in the management of patients with complex hydrocephalus and may reduce the need for shunt revision for headache. Non-haemorrhagic, post-shunting, subdural collections identified on routine postoperative CT may be treated by reprogramming.

Assessment of critical closing pressure in the cerebral circulation as a measure of cerebrovascular tone.

Critical closing pressure (CCP) calculated from the blood flow velocity (FV) and arterial blood pressure (ABP) waveforms has been previously reported to be useful in the assessment of the dynamics of cerebral circulation. We investigated the relationship between CCP and intracranial pressure (ICP) and cerebrovascular tone in a model of intracranial hypertension in 22 anaesthetised New Zealand White rabbits during manipulations of arterial CO2, ABP and vasodilatation caused by hypoxia. Recordings were made of FV in the basilar artery, ABP and ICP during subarachnoid infusion of saline. During infusion ICP and CCP were significantly correlated (R=0.68; p<0.001), but the magnitude of increase in ICP and CCP during infusion were not correlated to each other. Linear regression between the difference: CCP-ICP (representing a factor due to vasogenic tone) and cerebral perfusion pressure (CPP=ABP-ICP) was highly significant (R=-0.87; p<0.01). Generally, CCP decreased significantly (p<0.05) with hypercarbia, arterial hypotension and after and post-hypoxia and the difference: CCP-ICP decreased consistently after each vasodilatatory manoeuvre studied. Our data confirmed the linear relationship between CCP and ICP, and between the difference: CCP-ICP and cerebrovascular tone. However, because the magnitude of increase in ICP was not correlated to magnitude of change in CCP, CCP cannot be use for detection of increasing ICP quantitatively.

Vascular components of cerebrospinal fluid compensation.

OBJECT: The aim of the study was to assess how cerebrospinal fluid (CSF) pressure-volume compensation depends on cerebrovascular tone. METHODS: In 26 New Zealand White rabbits, intracranial pressure (ICP), arterial blood pressure, and basilar artery blood flow velocity were measured continuously. Saline was infused into the cranial subarachnoid space to assess CSF compensatory parameters: the resistance to CSF outflow, the elastance coefficient, and the amplitude of the ICP pulsatile waveform. Infusions were repeated on two different levels of CO2 concentration in the arterial blood (PaCO2), at normotension and hypotension, and after the death of the animal. An increase in PaCO2 from a mean of 27 to 48 mm Hg was accompanied by an 18% increase in the resistance to CSF outflow (p<0.005) and a 64% increase (p<0.05) in the elastance coefficient. A decrease in arterial blood pressure from a mean of 100 to 51 mm Hg caused a 25% decrease in CSF outflow resistance (p<0.01) but did not affect the elastance coefficient. Postmortem, a 23% decrease in the CSF outflow resistance was associated with a 102% decrease in the elastance coefficient. CONCLUSIONS: Cerebrovascular parameters have a limited but significant impact on CSF infusion studies. The vascular component of ICP may be identified as a significant factor contributing to this phenomenon. During infusion studies, physiological parameters influencing vascular conditions should be maintained as stable as possible.

Increase in transcranial Doppler pulsatility index does not indicate the lower limit of cerebral autoregulation.

INTRODUCTION: Transcranial Doppler pulsatility index was reported clinically to increase when cerebral perfusion pressure decreased, hypothetically marking the lower limit of cerebral autoregulation. We sought to investigate the relationship between pulsatility index, cerenbrovascular resistance, and cerebral perfusion pressure in various states of autoregulation in an animal model of moderate intracranial hypertension. METHOD: Eight New-Zealand White Rabbits were studied with basilar artery blood flow velocity (ultrasound Doppler) and cortical blood flow (laser Doppler) monitored continuously during subarachnoid saline infusion to increase intracranial pressure (< 55 mm Hg). Four animals demonstrated a stable cortical blood flow, and four demonstrated decreasing blood flow when cerebral perfusion pressure decreased. RESULTS: Pulsatility index showed the same pattern of increase when cerebral perfusion pressure decreased, independent on whether cortical blood flow was stable or falling. The percentage rate of increase in the pulsatility index was not different in autoregulating and non autoregulating animals. The rate of decrease in cerebrovascular resistance was significantly lower (p < 0.05) in non-autoregulating than in autoregulating animals. CONCLUSION: The increase in transcranial Doppler pulsatility index when cerebral perfusion pressure falls cannot be interpreted as a phenomenon able to mark the lower limit of cerebral autoregulation.

Posture-related overdrainage: comparison of the performance of 10 hydrocephalus shunts in vitro.

OBJECTIVE: Approximately 10 to 30% of shunt revisions may be attributed to posture-related overdrainage. The susceptibility of various hydrocephalus shunts to overdrainage of cerebrospinal fluid requires independent laboratory evaluation. METHODS: Shunts were tested in vitro by using precise computer-controlled equipment that was able to evaluate pressure-flow performance curves under various conditions. Hydrodynamic resistance and opening, closing, and operational pressures were evaluated for at least 28 days with normal (atmospheric) and decreased (-23 mm Hg, based on the International Standard Organization/Draft International Standard 7197 standard, which simulates conditions in upright body positions) outlet pressures. RESULTS: Ten different models of valves have been tested to date (Medtronic PS Medical Delta valve, flow-control valve, and lumboperitoneal shunt, Heyer-Schulte in-line, low-profile, and Pudenz flushing valves, Codman-Medos programmable and nonprogrammable valves, Sophy programmable valve, and Cordis Orbis-Sigma valve). The majority of these valves produced significantly negative (less than -10 mm Hg) average intracranial pressures in vertical body positions. In conjunction with nonphysiologically low hydrodynamic resistance (with the exception of the Orbis-Sigma valve, Medtronic PS Medical lumboperitoneal shunt, and Heyer-Schulte in-line valve), this may result in overdrainage related to body posture. The clinically reported rate of complications related to overdrainage is probably reduced by the long distal catheter, which increases the resistance of these valves by 100 to 200%. A few shunts (the Delta valve, low-profile valve, and Pudenz flushing valve with anti-siphon devices) offer reasonable resistance to negative outlet pressure, preventing complications related to overdrainage, but all valves with siphon-preventing devices may be blocked by increased subcutaneous pressure. CONCLUSION: Shunts without mechanisms preventing very low intracranial pressure in vertical body positions should be identified and avoided for patients likely to develop complications related to cerebrospinal fluid overdrainage.

Changes in transcranial Doppler flow velocity waveform following inhibition of nitric oxide synthesis. Experimental study in anaesthetised rabbits.

BACKGROUND: Analysis of the transcranial Doppler blood flow velocity (FV) waveform is used clinically to detect changes in cerebral haemodynamic profile. Such changes may be initiated both by alterations in microvascular resistance and in the tone of the cerebral arteries. METHODS: The role of endothelial mechanisms was investigated using inhibition of NO synthesis by systemic administration of NG-nitro-L-arginine methyl ester (L-NAME, 6 mg/kg) followed by simultaneous monitoring of both basilar artery FV and cerebrocortical microcirculation (laser Doppler flowmetry, LDF) in anaesthetised, ventilated rabbits over 60 minutes. RESULTS: Arterial blood pressure (AP) increased significantly (p < 0.01) above baseline level in the second minute following L-NAME and remained elevated until the end of experiment. Time average mean and systolic FV decreased immediately following L-NAME injection, with the statistically significant (p < 0.01) decrease from the third minute. Diastolic FV did not show such radical changes. LDF exhibited a slow decrease with time becoming significantly lower than baseline (p < 0.01) at 50 min. CONCLUSION: A gradual decrease in cortical microcirculation preceded by a rapid reaction recorded in the TCD waveform implies that an increase in the tone of the great cerebral arteries is the predominant phenomenon seen during the acute phase of NO synthase inhibition.

Contribution of mathematical modelling to the interpretation of bedside tests of cerebrovascular autoregulation.

OBJECTIVES: Cerebral haemodynamic responses to short and longlasting episodes of decreased cerebral perfusion pressure contain information about the state of autoregulation of cerebral blood flow. Mathematical simulation may help to elucidate which of the indices, that can be derived using transcranial Doppler ultrasonography and trends of intracranial pressure and blood pressure, are useful in clinical tests of autoregulatory reserve. METHODS: Time dependent interactions between pressure, flow, and volume of cerebral blood and CSF were modelled using a set of non-linear differential equations. The model simulates changes in arterial blood inflow and storage, arteriolar and capillary blood flow controlled by cerebral autoregulation, venous blood storage and venous outflow modulated by changes in ICP, and CSF storage and reabsorption. The model was used to simulate patterns of blood flow during either short or longlasting decreases in cerebral perfusion pressure. These simulations can be considered as clinically equivalent to a short compression of the common carotid artery, systemic hypotension, and intracranial hypertension. Simulations were performed in autoregulating and non-autoregulating systems and compared with recordings obtained in patients. RESULTS: After brief compression of the common carotid artery, a subsequent transient hyperaemia can be interpreted as evidence of intact autoregulation. During longlasting sustained hypoperfusion, a gradual increase in the systolic value of the blood flow velocity waveform along with a decrease in the diastolic value is specific for an autoregulating cerebrovascular system. CONCLUSION: Modelling studies help to interpret both clinical and experimental cerebral haemodynamic phenomena and their dependence on the state of autoregulation.

Relationship between transcranial Doppler-determined pulsatility index and cerebrovascular resistance: an experimental study.

Clinical studies with transcranial Doppler suggest that the pulsatility of the flow velocity (FV) waveform increases when the distal cerebrovascular resistance (CVR) increases. To clarify this relationship, the authors studied animal models in which the resistance may be decreased in a controlled manner by an increase in arterial CO2 tension, or by a decrease in cerebral perfusion pressure (CPP) in autoregulating animals. Twelve New Zealand white rabbits were anesthetized, paralyzed, and ventilated. Transcranial Doppler basilar artery FV, laser Doppler cortical blood flow, arterial pressure, intracranial pressure, and end-tidal CO2 concentration were measured continuously. Cerebrovascular resistance (CPP divided by laser Doppler cortical flux) and Gosling Pulsatility Index (PI, defined as an FV pulse amplitude divided by a timed average FV) were calculated as time-dependent variables for each animal. Four groups of animals undergoing controlled manipulations of CVR were analyzed. In Group I, arterial CO2 concentration was changed gradually from hypocapnia to hypercapnia. In Group II, gradual hemorrhagic hypotension was used to reduce CPP. In Group III, the short-acting ganglion blocking drug trimetaphan was injected intravenously to induce transient hypotension. Intracranial hypertension was produced by subarachnoid saline infusion in Group IV. During the hypercapnic challenge the correlation between the cortical resistance and Doppler flow pulsatility was positive (r = 0.77, p<0.001). In all three groups in which cerebral perfusion pressure was reduced a negative correlation between pulsatility index and cerebrovascular resistance was found (r = -0.84, p<0.001). The authors conclude that PI cannot be interpreted simply as an index of CVR in all circumstances.

Uncoupling of LCBF and LCGU in two different models of hydrocephalus: a review.

We have used two different experimental models to examine the relationship between local cerebral blood flow and metabolism in hydrocephalus. In our first experiments local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured by quantitative autoradiographic methods in adult rats rendered hydrocephalic, though asymptomatic, by the injection of kaolin intracisternally at 3 weeks of age and in control animals. There were no significant differences in LCGU or LCBF in any of the 29 areas of grey matter examined, including layer IV of the cerebral cortex. Scanning across the cerebral cortex revealed an appreciable fall in LCGU and LCBF towards the inside and the outside of the mantle in control animals. Hydrocephalus had no significant effect on this "transmantle" pattern of reduction in cortical metabolism towards the periphery, but in contrast, significantly enhanced the reduction in cortical blood flow in 7 out of the 10 cortical regions examined. Hence, in this model of asymptomatic hydrocephalus there is relative uncoupling of LCBF and LCGU in the inner and outer layers of the cerebral mantle. In a study performed in congenitally hydrocephalic H-Tx rats at 10, 20 and 28 days we found that uptake of deoxyglucose was impaired in hydrocephalic rats compared with their non-hydrocephalic siblings. Small changes were seen at 10 and 21 days, but statistically significant changes were seen only at 28 days. A small reduction in LCBF was observed in all regions at 10 days, with statistically significant differences between control and hydrocephalic rats in auditory and parietal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Early metabolic changes during m-Dinitrobenzene neurotoxicity and the possible role of oxidative stress.

m-Dinitrobenzene (m-DNB) is an industrial chemical causing gliovascular lesions in the brain stem similar to those produced by nitroimidazoles and by thiamine deficiency. To identify early preneuropathic indices of toxicity we examined the action of m-DNB on glycolysis and on measures of oxidative stress in the brain both in vivo and in vitro. Significant increases in local cerebral glucose utilization were seen in 14 of 30 brain regions prior to development of lesions. Rat brain astrocyte cultures also showed increases in both glucose consumption and lactic acid formation in the first 24 h following exposure to 0.5 mM m-DNB and prior to the development of cytotoxicity. The concentration of reduced glutathione in these cultures was decreased to about half of control values over a 2-h incubation period, indicating an early disturbance of redox balance. The rate of reduction of nitroblue tetrazolium increased eightfold during a 1-h incubation period, suggesting a free radical-mediated process. Superoxide dismutase partially prevented this increase, although other protective agents failed to do so possibly due to lack of cellular penetration. These observations show that m-DNB neurotoxicity involves early metabolic stimulation and redox disruption that may be causally associated with the production of free radicals.

Estimation of laser-Doppler flux biological zero using basilar artery flow velocity in the rabbit.

Laser-Doppler flowmetry has potential for continuous cerebral blood flow (CBF) measurement in man and experimental animals. However, laser-Doppler flux (LDFx) measured when perfusion is absent (the biological zero, 0biol) does not necessarily coincide with the instrument's electrical zero. To evaluate laser-Doppler flowmetry further we have compared LDFx in rabbits with continuous measurement of the maximum flow velocity (FVx) in the basilar artery using Doppler ultrasonography. Arterial blood pressure (ABP), FVx, and LDFx were measured continuously in anesthetized New Zealand White rabbits. ABP was altered by controlled hemorrhage with subsequent reinfusion. 0biol was estimated from regression analysis of FVx vs. LDFx and compared with 0biol obtained after death. There was a strong linear relationship between LDFx and FVx (r = 0.94). The absolute difference between estimated 0biol and true 0biol was 5.24% of control prehemorrhage LDFx. Variations in 0biol (range 4-409) suggest that percent changes in LDFx must be related to 0biol if results between individual animals are to be compared.