What comes first? The dynamics of cerebral oxygenation and blood flow in response to changes in arterial pressure and intracranial pressure after head injury.

BACKGROUND: Brain tissue partial oxygen pressure (Pbt(O(2))) and near-infrared spectroscopy (NIRS) are novel methods to evaluate cerebral oxygenation. We studied the response patterns of Pbt(O(2)), NIRS, and cerebral blood flow velocity (CBFV) to changes in arterial pressure (AP) and intracranial pressure (ICP). METHODS: Digital recordings of multimodal brain monitoring from 42 head-injured patients were retrospectively analysed. Response latencies and patterns of Pbt(O(2)), NIRS-derived parameters [tissue oxygenation index (TOI) and total haemoglobin index (THI)], and CBFV reactions to fluctuations of AP and ICP were studied. RESULTS: One hundred and twenty-one events were identified. In reaction to alterations of AP, ICP reacted first [4.3 s; inter-quartile range (IQR) -4.9 to 22.0 s, followed by NIRS-derived parameters and CBFV (10.9 s; IQR: -5.9 to 39.6 s, 12.1 s; IQR: -3.0 to 49.1 s, 14.7 s; IQR: -8.8 to 52.3 s for THI, CBFV, and TOI, respectively), with Pbt(O(2)) reacting last (39.6 s; IQR: 16.4 to 66.0 s). The differences in reaction time between NIRS parameters and Pbt(O(2)) were significant (P<0.001). Similarly when reactions to ICP changes were analysed, NIRS parameters preceded Pbt(O(2)) (7.1 s; IQR: -8.8 to 195.0 s, 18.1 s; IQR: -20.6 to 80.7 s, 22.9 s; IQR: 11.0 to 53.0 s for THI, TOI, and Pbt(O(2)), respectively). Two main patterns of responses to AP changes were identified. With preserved cerebrovascular reactivity, TOI and Pbt(O(2)) followed the direction of AP. With impaired cerebrovascular reactivity, TOI and Pbt(O(2)) decreased while AP and ICP increased. In 77% of events, the direction of TOI changes was concordant with Pbt(O(2)). CONCLUSIONS: NIRS and transcranial Doppler signals reacted first to AP and ICP changes. The reaction of Pbt(O(2)) is delayed. The results imply that the analysed modalities monitor different stages of cerebral oxygenation.

Cerebral arterial compliance in patients with internal carotid artery disease.

BACKGROUND: A decrease in arterial compliance of the internal carotid artery has been associated with an increased risk in ipsilateral ischaemic stroke. However, so far, no technique has been validated to monitor the compliance of intracerebral arteries (Ca) in patients with carotid artery disease. In this study, we sought to monitor Ca in patients with unilateral symptomatic disease and to determine its variations during changes in PaCO(2). METHODS: We studied 18 patients with unilateral symptomatic internal carotid artery stenosis >50% or occlusion. Patients underwent monitoring of arterial blood pressure (ABP) and middle cerebral artery cerebral blood flow velocities (CBFV) during baseline, hyperventilation and 5%CO(2) inhalation. Ca was calculated from pulsatile amplitudes of ABP and Cerebral arterial blood volume, extracted from the CBFV waveform using a new mathematical model. RESULTS: At baseline, the decrease in Ca on the diseased side was correlated with the degree of stenosis (r = -0.35; P = 0.01). During hypocapnia, Ca was lower compared to baseline on the normal side (P = 0.004) and on the diseased side (P = 0.04). Ca reactivity, reflecting the changes in Ca per changes in 1 mmHg PaCO(2), was lower on the diseased side between baseline and hypocapnia (3.4 vs. 2.6%; P = 0.04). During hypercapnia, no changes in Ca on the diseased (P = 0.8) nor on the normal sides (P = 0.2) were observed. CONCLUSIONS: The decrease in cerebral arterial compliance the side of stenosis/occlusion was correlated with the severity of the internal carotid artery disease. Further studies are needed to determine whether Ca may improve the prediction of ischaemic events in symptomatic and asymptomatic patients.

High flow extra-cranial to intra-cranial bypass for complex internal carotid aneurysms.

Cerebral revascularisation with extracranial - intracranial (EC-IC) bypass is generally indicated in patients with complex anterior circulation aneurysms who have failed parent artery occlusion. We report on the process and outcome of our early experience of performing high flow bypass in patients with complex anterior circulation aneurysms. We have reviewed patients who have undergone an EC-IC bypass for treatment of complex anterior circulation aneurysms, and report our outcome on graft patency, surgical complications, discharge destination, and obliteration rates. Nine patients that underwent 11 bypasses are described. Seven patients had a giant saccular aneurysm of the carotid, and these were all obliterated on post-operative imaging. Two patients presenting with an intracranial carotid dissection required trapping of the diseased segment following the bypass. The overall graft patency rate was 88%. One patient developed a post operative subdural collection (managed conservatively), and one patient required early graft revision. Discharge destination was home in 8/9 patients. There was no mortality. Although EC-IC bypass is a technically challenging procedure, it provides a valuable treatment option for patients with complex anterior circulation aneurysms. Good graft patency rates can be achieved with low surgical morbidity in patients with a disease process that otherwise attracts a highly unfavourable natural history.

High flow extracranial to intracranial vascular bypass procedure for giant aneurysms: indications, surgical technique, complications and outcome.

High flow extracranial-intracranial (hfEC-IC) vascular bypass remains an important surgical technique in selected patients. For example, in those with giant aneurysms where the natural history of the condition is poor, and direct surgical approaches are recognised as excessively hazardous. hfEC-IC also allows for major carotid vessel occlusion in the treatment of skull base tumours which would otherwise be untreatable. We describe the indications, techniques, complications, and outcomes of this procedure in an era where few neurosurgeons are exposed to high volume vascular neurosurgery, and fewer still are trained to perform hfEC-IC. We emphasise the need for a stereo-typed and meticulous technique, highlighting key points at each stage of the operation, to ensure graft survival and minimal chances of morbidity.

Graft aneurysm complicating an extracranial-intracranial bypass.

We report a patient that developed an aneurysm on a grafted saphenous vein following an extracranial-intracranial (EC-IC) bypass. Although saphenous vein graft aneurysms (SVGAs) have been described as a rare complication following coronary surgery, we are unaware of any previously reported cases of SVGAs following EC-IC bypass.

Characterisation of carotid atheroma in symptomatic and asymptomatic patients using high resolution MRI.

BACKGROUND AND PURPOSE: To prospectively evaluate differences in carotid plaque characteristics in symptomatic and asymptomatic patients using high resolution MRI. METHODS: 20 symptomatic and 20 asymptomatic patients, with at least 50% carotid stenosis as determined by Doppler ultrasound, underwent preoperative in vivo multispectral MRI of the carotid arteries. Studies were analysed both qualitatively and quantitatively in a randomised manner by two experienced readers in consensus, blinded to clinical status, and plaques were classified according to the modified American Heart Association (AHA) criteria. RESULTS: After exclusion of poor quality images, 109 MRI sections in 18 symptomatic and 19 asymptomatic patients were available for analysis. There were no significant differences in mean luminal stenosis severity (72.9% vs 67.6%; p = 0.09) or plaque burden (median plaque areas 50 mm(2) vs 50 mm(2); p = 0.858) between the symptomatic and asymptomatic groups. However, symptomatic lesions had a higher incidence of ruptured fibrous caps (36.5% vs 8.7%; p = 0.004), haemorrhage or thrombus (46.5% vs 14.0%; p<0.001), large necrotic lipid cores (63.8% vs 28.0%; p = 0.002) and complicated type VI AHA lesions (61.5% vs 28.1%; p = 0.001) compared with asymptomatic lesions. The MRI findings of plaque haemorrhage or thrombus had an odds ratio of 5.25 (95% CI 2.08 to 13.24) while thin or ruptured fibrous cap (as opposed to a thick fibrous cap) had an odds ratio of 7.94 (95% CI 2.93 to 21.51) for prediction of symptomatic clinical status. CONCLUSIONS: There are significant differences in plaque characteristics between symptomatic and asymptomatic carotid atheroma and these can be detected in vivo by high resolution MRI.

Ventriculostomy for control of raised ICP in acute traumatic brain injury.

UNLABELLED: The aim of this study was to evaluate the effect of ventriculostomy on intracranial pressure (ICP), and related parameters, including cerebrospinal compensation, cerebral oxygenation (PbtO2) and metabolism (microdialysis) in patients with traumatic brain injury (TBI). MATERIALS AND METHODS: Twenty-four patients with parenchymal ICP sensors were prospectively included in the study. Ventriculostomy was performed after failure to control ICP with initial measures. Monitoring parameters were digitally recorded before and after ventriculostomy and compared using appropriate tests. RESULTS: In all patients ventriculostomy led to rapid reduction in ICP. Pooled mean daily values of ICP remained < 20mmHg for 72h after ventriculostomy and were lower than before (p < 0.001). In 11 out of 24 patients during the initial 24-h period following ventriculostomy an increase in ICP to values exceeding 20mmHg was observed. In the remaining 13 patients ICP remained stable, allowing reduction in the intensity of treatment. In this group ventriculostomy led to significant improvement in craniospinal compensation (RAP index), cerebral perfusion pressure and PbtO2. Improvement in lactate/pyruvate ratio, a marker of energy metabolism, was correlated with the increase in PbtO2. CONCLUSION: Ventriculostomy is a useful ICP-lowering manoeuvre, with sustained ICP reduction and related physiological improvements achieved in > 50% of patients.

Effects of fluid therapy following aneurysmal subarachnoid haemorrhage: a prospective clinical study.

Blood transfusions and intravenous fluids are commonly employed as rescue therapy for delayed cerebral ischaemia following aneurysmal subarachnoid haemorrhage (aSAH). We sought to determine effects of various fluid supplements on clinical outcome in patients following aSAH. Clinical events and laboratory data of 160 aSAH patients were prospectively collected as part of 2 randomised controlled trials. Outcomes at discharge and at 6 months were measured with Glasgow Outcome Scale (GOS). Favourable outcome was defined as good recovery or moderate disability on GOS. All of the 160 patients received intravenous fluid supplements with crystalloids; 122 (76.3%) also received synthetic colloids (4% succinylated gelatine or 6% pentastarch). A higher daily dose of synthetic colloids for initial resuscitation seemed to be associated with more requirements for blood transfusions (p = 0.003) and occurrence of vasospasm in poor-grade patients (p = 0.081), but blood transfusions themselves were not associated with occurrence of vasospasm. Compared with patients not receiving synthetic colloids, those receiving synthetic colloids had increased haemodilution, elevated inflammatory profiles, and decreased duration and strength of intact cerebral autoregulation. Multivariate analyses identified that blood transfusions (odds ratio, OR 3.38, p = 0.035) were associated with unfavourable outcome at discharge. Colloid fluids (OR 2.53/L/day, p = 0.025) promoted unfavourable outcome at 6 months (OR 4.45, p = 0.035), while crystalloids decreased unfavourable outcome (OR 0.27/L/day, p = 0.005). Associations between synthetic colloids and crystalloids with GOS at 6 months were dose-related. Intravenous fluid therapy using synthetic colloids or blood transfusions may be associated with increased unfavourable outcome following aSAH.

The management of primary chronic subdural haematoma: a questionnaire survey of practice in the United Kingdom and the Republic of Ireland.

A wide range of treatment modalities are employed in the treatment of chronic subdural haematoma (CSDH). A rational and evidence-based treatment strategy has the potential to optimise treatment for the individual patient and save resources. The aim of this study was to survey aspects of current practice in the UK and Ireland. A 1-page postal questionnaire addressing the treatment of primary (i.e. not recurrent) CSDH was sent to consultant SBNS members in March 2006. There were 112 responses from 215 questionnaires (52%). The preferred surgical technique was burr hole drainage (92%). Most surgeons prefer not to place a drain, with 27% never using one and 58% using drain only in one-quarter of cases or less. Only 11% of surgeons always place a drain, and only 30% place one in 75% of cases or more. The closed subdural-to-external drainage was most commonly used (91%) with closed subgaleal-to-external and subdural-to-peritoneal conduit used less often (3 and 4%, respectively). Only 5% of responders claimed to know the exact recurrence rate. The average perceived recurrence rate among the surgeons that never use drains and those who always use drains, was the same (both 11%). Most operations are performed by registrars (77%). Postoperative imaging is requested routinely by 32% of respondents and 57% of surgeons prescribe bed rest. Ninety four per cent surgeons employ conservative management in less than one-quarter of cases. Forty-two per cent of surgeons never prescribe steroids, 55% prescribe them to those managed conservatively. This survey demonstrates that there are diverse practices in the management of CSDH. This may be because of sufficiently persuasive evidence either does not exist or is not always taken into account. The current literature provides Class II and III evidence and there is a need for randomized studies to address the role of external drainage, steroids and postoperative bed rest.

Predictive value of initial clinical status, intracranial pressure and transcranial Doppler pulsatility after subarachnoid haemorrhage.

BACKGROUND: We examined the predictive value of initial clinical status, mean arterial blood pressure (MABP), intracranial pressure (ICP) and transcranial Doppler (TCD)-derived pulsatility and resistance indices for outcome and quality of life one year following aneurysmal subarachnoid haemorrhage (SAH). METHOD: Neuromonitoring was performed in 29 patients following clipping or coiling of an aneurysm. Mean arterial blood pressure was measured in the radial artery and intracranial pressure was assessed via a closed external ventricular drainage. Based on transcranial Doppler-recordings of the middle cerebral artery, Gosling's pulsatility (PI) and Pourcelot's resistance (RI) index were calculated. Glasgow outcome score (GOS) and short form-36 (SF-36) scores were determined one year after SAH. FINDINGS: An unfavourable outcome (GOS 1-3) was observed in 34% of patients and correlated significantly (p < 0.05) with a poor initial clinical status, as determined by Glasgow Coma Scale (r = 0.55), Hunt and Hess (r = -0.62), World Federation of Neurosurgical Societies (WFNS) (r = -0.48) and Fisher (r = -0.58) score. Poor outcome was significantly associated with high mean arterial blood pressure (r = -0.44) and intracranial pressure (r = -0.48) as well as increased pulsatility (r = -0.46) and resistance (r = -0.43) indices. Hunt and Hess grade > or = 4 (OR 12.4, 5-95% CI: 1.9-82.3), mean arterial blood pressure > 95 mmHg (19.5, 2.9-132.3), Gosling's pulsatility >0.8 (6.5, 1.6-27.1) and Pourcelot's resistance >0.57 (15.4, 2.3-103.4) were predictive for unfavourable outcome in logistic regression, however TCD-diagnosed vasospasm was not. Except for mental health, significantly reduced scores were observed in all short form-36 domains. Initial clinical status correlated significantly with the physical functioning, role physical, bodily pain, social functioning and physical component summary of short form-36. CONCLUSIONS: Mortality and morbidity following SAH remains high, especially in poor-grade patients. Outcome is mainly correlated with initial clinical status, mean arterial blood pressure, intracranial pressure, pulsatility and resistance indices. Those factors seem to be stronger than the influence of vasospasm.

Decompressive craniectomy in traumatic brain injury: outcome following protocol-driven therapy.

Although decompressive craniectomy following traumatic brain injury is an option in patients with raised intracranial pressure (ICP) refractory to medical measures, its effect on clinical outcome remains unclear. The aim of this study was to evaluate the outcome of patients undergoing this procedure as part of protocol-driven therapy between 2000-2003. This was an observational study combining case note analysis and follow-up. Outcome was assessed at an interval of at least 6 months following injury using the Glasgow Outcome Scale (GOS) score and the SF-36 quality of life questionnaire. Forty-nine patients underwent decompressive craniectomy for raised and refractory ICP (41 [83.7%] bilateral craniectomy and 8 [16.3%] unilateral). Using the Glasgow Coma Scale (GCS), the presenting head injury grade was severe (GCS 3-8) in 40 (81.6%) patients, moderate (GCS 9-12) in 8 (16.3%) patients, and initially mild (GCS 13-15) in 1 (2.0%) patient. At follow-up, 30 (61.2%) patients had a favorable outcome (good recovery or moderate disability), 10 (20.48) remained severely disabled, and 9 (18.4%) died. No patients were left in a vegetative state. Overall the results demonstrated that decompressive craniectomy, when applied as part of protocol-driven therapy, yields a satisfactory rate of favorable outcome. Formal prospective randomized studies of decompressive craniectomy are now indicated.

Decompressive craniectomy in traumatic brain injury: the randomized multicenter RESCUEicp study (www.RESCUEicp.com).

The RESCUEicp (Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of intracranial pressure) study has been established to determine whether decompressive craniectomy has a role in the management of patients with traumatic brain injury and raised intracranial pressure that does not respond to initial treatment measures. We describe the concept of decompressive craniectomy in traumatic brain injury and the rationale and protocol of the RESCUEicp study.

Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography.

BACKGROUND: Atherosclerotic plaque rupture is usually a consequence of inflammatory cell activity within the plaque. Current imaging techniques provide anatomic data but no indication of plaque inflammation. The glucose analogue [18F]-fluorodeoxyglucose (18FDG) can be used to image inflammatory cell activity non-invasively by PET. In this study we tested whether 18FDG-PET imaging can identify inflammation within carotid artery atherosclerotic plaques. METHODS AND RESULTS: Eight patients with symptomatic carotid atherosclerosis were imaged using 18FDG-PET and co-registered CT. Symptomatic carotid plaques were visible in 18FDG-PET images acquired 3 hours post-18FDG injection. The estimated net 18FDG accumulation rate (plaque/integral plasma) in symptomatic lesions was 27% higher than in contralateral asymptomatic lesions. There was no measurable 18FDG uptake into normal carotid arteries. Autoradiography of excised plaques confirmed accumulation of deoxyglucose in macrophage-rich areas of the plaque. CONCLUSIONS: This study demonstrates that atherosclerotic plaque inflammation can be imaged with 18FDG-PET, and that symptomatic, unstable plaques accumulate more 18FDG than asymptomatic lesions.

Extracellular amino acid changes in patients during reversible cerebral ischaemia.

This study investigated the changes in extracellular chemistry during reversible human cerebral ischaemia. Delayed analysis was performed on samples taken from a subgroup of patients during aneurysm surgery previously reported. Frozen microdialysis samples from 14 patients who had all undergone temporary clipping of the ipsilateral internal carotid artery (ICA) were analysed for another 15 amino acids with HPLC and for glycerol with CMA-600. Changes were characterised according to whether cerebral tissue oxygen pressure (PBO2) decreases were brief or prolonged. Brief ICA clipping (maximum duration of 16 minutes) in 11 patients was not associated with changes in amino acids or glycerol. Cerebral ischaemia, defined by a PBO2 decrease below 1.1 kPa for at least 30 minutes during ICA occlusion, occurred in 3 patients. None of whom developed an infarct in the monitored region. This prolonged reversible ischaemia was associated with transient delayed increases in gamma-amino butyric acid (GABA) as well as glutamate and glycerol, each by two-to-three folds. This study demonstrates detectable transient increases in human extracellular glutamate, GABA and glycerol during identified periods of reversible cerebral ischaemia, maximal 30-60 minutes after onset of ischaemia, but not in other amino acids detected by HPLC.

Cerebral blood flow augmentation in patients with severe subarachnoid haemorrhage.

Following aneurysmal subarachnoid haemorrhage (SAH), cerebral blood flow (CBF) may be reduced, resulting in poor outcome due to cerebral ischaemia and subsequent stroke. Hypertonic saline (HS) is known to be effective in reducing intracranial pressure (ICP). We have previously shown a 20-50% increase in CBF in ischaemic regions after intravenous infusion of HS. This study aims to determine the effect of HS on CBF augmentation, substrate delivery and metabolism. Continuous monitoring of arterial blood pressure (ABP), ICP, cerebral perfusion pressure (CPP), brain tissue oxygen (PbO2), middle cerebral artery flow velocity (FV), and microdialysis was performed in 14 poor grade SAH patients. Patients were given an infusion of 23.5% HS, and quantified xenon computerised tomography scanning (XeCT) was carried out before and after the infusion in 9 patients. The results showed a significant increase in ABP, CPP, FV and PbO2, and a significant decrease in ICP (p < 0.05). Nine patients showed a decrease in lactate-pyruvate ratio at 60 minutes following HS infusion. These results show that HS safely and effectively augments CBF in patients with poor grade SAH and significantly improves cerebral oxygenation. An improvement in cerebral metabolic status in terms of lactate-pyruvate ratio is also associated with HS infusion.

Evaluation of a near-infrared spectrometer (NIRO 300) for the detection of intracranial oxygenation changes in the adult head.

BACKGROUND AND PURPOSE: The clinical application of intracranial near-infrared spectroscopy in adults has been hampered by concerns over contamination from extracranial tissues. The NIRO 300 (Hamamatsu Photonics) provides continuous online measurements of hemoglobin and cytochrome oxidase concentrations and a calculated tissue oxygen index (TOI). The present study seeks confirmation of the anatomic source of TOI in the adult cranium. METHODS: Sixty patients undergoing carotid endarterectomy were studied. The NIRO 300 was incorporated into an established multimodal monitoring system. TOI, oxyhemoglobin, and deoxyhemoglobin changes were assessed and compared with (1) frontal cutaneous laser-Doppler flowmetry and (2) transcranial Doppler measurement of the ipsilateral middle cerebral artery flow velocity. RESULTS: Changes in TOI were seen during cross-clamping of the carotid vessels in 49 patients (mean DeltaTOI=-9.4%, SD=7.1). Significant correlation was seen between TOI and flow velocity (r=0.56) but not with laser-Doppler flowmetry (r=0.13). In 31 patients, oxyhemoglobin and deoxyhemoglobin concentrations were recorded, showing significant changes during both external carotid artery and internal carotid artery clamping. A change in TOI was predominantly associated with internal carotid artery clamping (n=41). When TOI changed during external carotid artery clamping (n=8), significant blood pressure changes occurred, or extracranial-to-intracranial anastomosis was evident. In the absence of such variables, the sensitivity of TOI to intracranial and extracranial changes was 87.5% and 0%, respectively, and specificity was 100% and 0%, respectively. CONCLUSIONS: The NIRO 300 reflects changes in cerebral tissue oxygenation when TOI is calculated, with a high degree of sensitivity and specificity.

Cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate in the cerebrospinal fluid of man: relation to blood levels and the effects of age.

The relation between blood and cerebrospinal fluid (CSF) concentrations of cortisol, dehydroepiandrosterone (DHEA), and its sulfate (DHEAS) was measured in 62 subjects aged 3-85 yr old, fitted with ventriculo-peritoneal or lumbar-peritoneal shunts for a variety of diagnoses. There were 36 males and 36 females. Forty-eight subjects were not taking exogenous corticosteroids; the other 14 were receiving either systemic or local steroids. A single sample of blood and CSF was taken from each subject within 10 min for measurement of cortisol, DHEA, and DHEAS. The proportional levels of cortisol (5.8%) and DHEA (5.4%) in the CSF compared with those in the blood were similar in subjects not taking steroids. However, CSF DHEAS levels were only 0.15% of those in the blood. Because DHEAS blood levels were so much greater than DHEA, DHEAS in the CSF was still higher than DHEA despite the reduced penetration of the sulfated steroid. The blood/CSF ratios were similar in subjects taking steroids. There were significant correlations in steroid-free subjects between blood and CSF levels for DHEA (r = 0.65) and DHEAS (r = 0.88) but not for cortisol (r = 0.26). Steroid treatment significantly lowered blood cortisol, DHEA and DHEAS, and CSF DHEA, but not CSF cortisol or DHEAS compared with an age- and sex-matched sample of steroid-free subjects. In steroid-free adults (18 yr and over; n = 37), blood cortisol showed no age-related change. However, CSF cortisol was markedly raised in a proportion of steroid-free subjects over the age of 60 yr. Levels of corticoid-binding globulin in plasma did not alter with age. As expected, there were significant age-related decrements in both blood DHEA and DHEAS. CSF DHEA (r = 0.42) and CSF DHEAS (r = 0.39) were significantly negatively correlated with age. In steroid-free juveniles (n = 11) there were no age-related changes in either blood or CSF cortisol, but significant increases with age in DHEA and DHEAS in both blood and CSF. Calculation of the cortisol/DHEA and cortisol/ DHEAS molar ratios in the CSF showed both to be raised in the very young (3-8 yr) and the elderly (60 yr and over) by a factor of 4-5 compared with young adults aged 18-39. There were no sex differences in any of the parameters measured. These findings show that the relation between levels in the blood and CSF differ for each of these three neuroactive steroids. The brain is exposed to relatively high levels of DHEA and DHEAS during later childhood and early adulthood but to relatively or absolutely high levels of cortisol during infancy and older age. In view of the known antiglucocorticoid action of DHEA and DHEAS, and the direct action of these steroids on membrane-bound transmitter events (such as gamma-aminobutyric acidA receptors), these changes may have important implications for age-related alterations in brain function.

A feedback-controlled pump produces stable hypotension in anaesthetised rabbits.

A method is described for the reliable production of controlled hypotension in experimental animals. Reduction in arterial blood pressure was obtained in rabbits by withdrawing arterial blood using a computer-driven pump operating within a feedback control system. Arterial blood pressure, blood flow velocity in the basilar artery (measured using transcranial Doppler), and anterior cortical microcirculation (measured using laser Doppler) were monitored. The aim of the experiments was to compare stability of hypotension produced using arterial blood pressure or basilar flow velocity as feedback control variables. Basilar artery flow velocity provided the most stable profound hypotension and during reinfusion when animals were not autoregulating. However, arterial blood pressure provided the most accurate stepwise control in autoregulating animals.

Digital imaging of umbelliferone clearance: a method for repeated measurements of cerebral cortical blood flow with high temporal and spatial resolution.

We have developed a procedure for digital imaging of the exposed cerebral cortex during elution of a fluorescent dye. This avoids disturbing the cortex and has provided a method for the repeated estimation of regional CBF (rCBF) with a high topographical resolution. Under varying conditions of MABP and arterial blood gases, grey-level images of the exposed cortex irradiated with ultraviolet light (340 or 370 nm) were digitised (8 bits) at 15-s intervals after the injection of 1-2 ml of saturated umbelliferone solution into the lingual or external carotid artery of anaesthetised cats and rabbits. Specifically designed software allowed (a) regions of interest (ROIs) in the exposed cortex to be defined that were automatically applied to the sequence of images in a selected clearance and (b) solution of the initial slope equation for rCBF from the decay in grey-level fluorescence by exponential regression. Separate software that solved the equation at the level of a single pixel allowed a pseudocolour map of cortical rCBF to be generated. The factors affecting the resolution of this technique have been identified and quantified. Thus consistent and reproducible results were obtained provided that the fluorescence enhancement exceeded 20 grey levels and the r2 coefficient for regression was 90% or above. Mean rCBF values of 99.5 [95% confidence interval (CI), 89.4-110] ml 100 g-1 min-1 were obtained for rabbits (N = 12; mean MABP = 75.2; mean PaCO2 = 32.9; PaO2 = 111.8; pH 7.38) and 65.1 (95% CI, 55.1-75.1) ml 100 g-1 min-1 for cats (N = 8; mean MABP = 92.8; PaCO2 = 31.5; PaO2 = 114.6, pH 7.40).(ABSTRACT TRUNCATED AT 250 WORDS)