Peripheral venous lactate at admission is associated with in-hospital mortality, a prospective cohort study.

BACKGROUND: The prognostic value of blood lactate as a predictor of adverse outcome in the acutely ill patient is unclear. The aim of this study was to investigate if a peripheral venous lactate measurement, taken at admission, is associated with in-hospital mortality in acutely ill patients with all diagnosis. Furthermore, we wanted to investigate if the test improves a triage model in terms of predicting in-hospital mortality. METHODS: We retrieved a cohort of 2272 adult patients from a prospectively gathered acute admission database. We performed regression analysis to evaluate the association between the relevant covariates and the outcome measure: in-hospital mortality. RESULTS: Lactate as a continuous variable was a risk for in-hospital mortality with an odds ratio (OR) of 1.40 [95% confidence interval (CI) 1.25-1.57, P<0.0001]. OR for in-hospital mortality increased with increasing lactate levels from 2.97 (95% CI 1.55-5.72, P<0.001) for lactate between 2 mmol/l and 4 mmol/l, to 7.77 (95% CI 3.23-18.66, P<0.0001) for lactate>4 mmol/l. If the condition was non-compensated (i.e. pH<7.35), OR for in-hospital mortality increased to 19.99 (7.26-55.06, P<0.0001). Patient with a blood lactate at 4 mmol/l or more had a risk of in-hospital mortality equivalent to the patients in the most urgent triage category. CONCLUSION: We found elevated admission peripheral venous lactate to be independently associated with in-hospital mortality in the acutely ill patient admitted to the emergency department. Patients with a lactate>4 mmol/l at hospital admission should be considered triaged to the most urgent triage category.

Hyperpolarized Metabolic MR in the Study of Cardiac Function and Disease.

Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR signal from a biological molecule of interest by more than 10,000 times, making it possible to measure its cellular uptake and conversion in specific enzymatic pathways in real time. We review the role of hyperpolarized MR in identifying changes in cardiac metabolism in vivo, and present the extensive literature on hyperpolarized pyruvate that has been used to characterize cardiac disease in various in vivo models, such as myocardial ischemia, hypertension, diabetes, hyperthyroidism and heart failure. The technical aspects of the technique are presented as well as the challenges of translating the technique into clinical practice. Hyperpolarized MR has the prospect of transforming diagnostic cardiology by offering new insights into cardiac disease and potentially even to contribute to personalized therapy based on a thorough understanding of the individual intracellular metabolism.

Application of stereological estimates in patients with severe head injuries using CT and MR scanning images.

Severe brain damage is often followed by serious complications. Quantitative measurements, such as regional volume and surface area under various conditions, are essential for understanding functional changes in the brain and assessing prognosis. The affected brain tissue is variable, hence traditional imaging methods are not always applicable and automatic methods may not be able to match the individual observer. Stereological techniques are alternative tools in the quantitative description of biological structures, and have been increasingly applied to the human brain. In the present study, we applied stereological techniques to representative CT and MRI brain scans from five patients to describe how stereological methods, when applied to scans of trauma patients, can provide a useful supplement to the estimation of structural brain changes in head injuries. The reliability of the estimates was tested by obtaining repeated intra- and interobserver estimates of selected subdivisions of the brain in patients with acute head injury, as well as in an MR phantom. The estimates of different subdivisions showed a coefficient of variation (CV) below 12% in the patients and below 7% for phantom estimation. The validity of phantom estimates was tested by the average deviation from the true geometric values, and was below 10%. The stereological methods were compared with more traditional region-based methods performed on medical imaging, which showed a CV below 7% and bias below 14%. It is concluded that the stereological estimates may be useful tools in head injury quantification.

A double-blind, randomized trial of IV immunoglobulin treatment in acute optic neuritis.

OBJECTIVE: To investigate if IV immunoglobulin (IVIG) treatment in the acute phase of optic neuritis (ON) could improve visual outcome and reduce MRI disease activity 6 months after onset of ON. METHODS: Sixty-eight patients with ON were randomized within 4 weeks from onset of symptoms. Thirty-four patients were randomized to IVIG 0.4 g/kg body wt, and 34 patients were randomized to placebo. Infusions were given at days 0, 1, 2, 30, and 60. Contrast sensitivity, visual acuity, and color vision were measured at baseline and after 1 week, 1 month, and 6 months. Pattern reversal visual evoked potential studies and gadolinium-enhanced MRI were performed at baseline and after 1 and 6 months. Clinical relapses during follow-up were recorded. RESULTS: There was no difference in the primary outcome, contrast sensitivity after 6 months, between patients randomized to treatment with IVIG or placebo. In addition, there was no significant difference in the secondary outcome measures, improvement in the visual function measures and MRI, at any time during follow-up. At baseline, a significantly higher number of patients in the IVIG group had one or more enhancing lesions on MRI and IVIG-treated patients had a significantly higher number of enhancing lesions on MRI than patients treated with placebo. No difference was found in number of patients with one or more enhancing lesions or number of enhancing lesions in subsequent scans between treatment groups. Number of relapses was equal in the two treatment groups during follow-up. CONCLUSIONS: There was no effect of IV immunoglobulin (IVIG) on long-term visual function following acute optic neuritis, nor was there an effect of IVIG treatment in reducing latency on visual evoked potentials and thus preserving function of axons of the optic nerve.

Nitric oxide synthase expression and enzymatic activity in multiple sclerosis.

We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant iNOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age and sex showed no such changes. Our data support the hypothesis that NO is a pathogenic factor in MS, and that NOS IR is strongly expressed in brain regions appearing normal by MRI.

Nitric oxide synthase expression and enzymatic activity in human brain tumors.

Nitric oxide (NO) is synthesized by NO synthases (NOS), existing in 3 isoforms. NO influences a great variety of vital functions including vascular tone and neurotransmission. Under conditions of excessive formation, NO emerges as an important mediator of neurotoxicity in a variety of disorders of the central nervous system (CNS). Inhibitors of NOS are available that may modify the activity of all isoforms, which may be of clinical relevance. The expression of the 3 NOS isoforms nNOS, iNOS and eNOS and NOS enzymatic activity was examined in 40 patients with primary CNS tumors (gliomas WHO grades I - IV and meningeomas WHO grades I - III) and in 13 patients with metastases from adenocarcinomas or malignant melanomas. A polyclonal antibody directed against nNOS and monoclonal antibodies directed against iNOS and eNOS were used for immunohistochemical staining. NOS enzymatic activity, measured by labeled arginine to citrulline conversion, was assessed in tissue specimens obtained from the same tumors. NOS data were compared with clinical variables and the degree of edema as judged from MR scanning. nNOS expression was increased in tumor cells of glial neoplasms and most pronounced in high-grade tumors, WHO grades III and IV, and in the carcinoma and melanoma metastases. Low-grade gliomas, WHO grades I and II and meningeomas expressed no or only little nNOS. iNOS was only expressed in a few tumors. eNOS was expressed sporadically in the tumor cells while the expression was increased in vascular endothelial cells in both the tumor itself and the peritumoral area of glial neoplasms, and in metastases. eNOS expression was sporadic in endothelial cells of meningeomas. NOS enzymatic activities were heterogeneous among tumor types (0 - 13.8 pmol/min/mg of protein) without correlation to the NOS expression found by immunohistochemical techniques. Likewise, NOS activity and expression was not correlated to the clinical scores or brain edema. In conclusion, nNOS expression may be a putative useful indicator of brain tumor differentiation and malignancy. The enhanced expression of eNOS in vascular endothelial cells of glial neoplasms and metastases raises the possibility that NO production in tumor endothelial cells may contribute to tumor blood flow regulation and possibly brain edema.

Nitric oxide synthase activity in human pituitary adenomas.

OBJECTIVES: The purpose of the present study was to examine human pituitary adenomas for nitric oxide synthase (NOS) activity by immunohistochemical and enzymatic methods. MATERIALS AND METHODS: Adenomatous tissue from 16 patients were obtained during operation and stained immunohistochemically for hormone production and for the three NOS isoenzymes. Cell types that expressed NOS immunoreactivity (IR) were identified, and the NOS isoform was noted. NOS activity was measured enzymatically by the conversion of L-arginine to L-citrulline in tissue samples. RESULTS: Endothelial cells of pituitary adenomas showed increase of eNOS IR compared with control tissue. The nNOS and iNOS IR were the same in adenomas and controls. There was no correlation between NOS IR and NOS activity measured enzymatically and the endocrine activity of the tumour or other clinical variables. CONCLUSION: The observation of increased eNOS IR in endothelial cells of adenomas may suggest that NO plays a role in the regulation of blood flow in pituitary adenomas.

Relationship of spikes, synaptic activity, and local changes of cerebral blood flow.

The coupling of electrical activity in the brain to changes in cerebral blood flow (CBF) is of interest because hemodynamic changes are used to track brain function. Recent studies, especially those investigating the cerebellar cortex, have shown that the spike rate in the principal target cell of a brain region (i.e. the efferent cell) does not affect vascular response amplitude. Subthreshold integrative synaptic processes trigger changes in the local microcirculation and local glucose consumption. The spatial specificity of the vascular response on the brain surface is limited because of the functional anatomy of the pial vessels. Within the cortex there is a characteristic laminar flow distribution, the largest changes of which are observed at the depth of maximal synaptic activity (i.e. layer IV) for an afferent input system. Under most conditions, increases in CBF are explained by activity in postsynaptic neurons, but presynaptic elements can contribute. Neurotransmitters do not mediate increases in CBF that are triggered by the concerted action of several second messenger molecules. It is important to distinguish between effective synaptic inhibition and deactivation that increase and decrease CBF and glucose consumption, respectively. In summary, hemodynamic changes evoked by neuronal activity depend on the afferent input function (i.e. all aspects of presynaptic and postsynaptic processing), but are totally independent of the efferent function (i.e., the spike rate of the same region). Thus, it is not possible to conclude whether the output level of activity of a region is increased based on brain maps that use blood-flow changes as markers.

Cortical spreading depression in migraine.

Cortical spreading depression (CSD) is associated with a dramatic failure of brain ion homeostasis as well as efflux of excitatory amino acids from nerve cells and increased energy metabolism. There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine. This paper will, based on the experience related to the detection of CSD in humans, discuss pitfalls and possible strategies for detection of CSD in man. Development of reliable methods for detection of CSD in humans will determine the extent to which the large body of experimental findings from animal studies of CSD can be applied to the investigation and treatment of human brain disease. The paper is based on the experience that has been gained from two decades of studies of CSD in relation to clinical neurological diseases.

Coupling and uncoupling of activity-dependent increases of neuronal activity and blood flow in rat somatosensory cortex.

1. Electrical stimulation of the infraorbital nerve was used to examine the coupling between neuronal activity and cerebral blood flow (CBF) in rat somatosensory cortex by laser Doppler flowmetry and extracellular recordings of field potentials. 2. The relationship between field potential (FP) and CBF amplitudes was examined as a function of the stimulus intensity (0--2.0 mA) at fixed frequency (3 Hz). FP amplitudes up to 2.0-2.5 mV were unaccompanied by increases of CBF. Above this threshold, CBF and FP amplitudes increased proportionally. 3. At fixed stimulus intensity of 1.5 mA, CBF increases were highly correlated to FP amplitudes at low frequencies of stimulation (< 2 Hz), but uncoupling was observed at stimulation frequencies of 2--5 Hz. The evoked responses were independent of stimulus duration (8--32 s). 4. The first rise in CBF occurred within the first 0.2 s after onset of stimulation in the upper 0--250 microm of the cortex. Latencies were longer (1.0--1.2 s) in lower cortical layers in which CBF and FP amplitudes were larger. 5. Local AMPA receptor blockade attenuated CBF and FP amplitudes proportionally. 6. This study showed that activity-dependent increases in neuronal activity and CBF were linearly coupled under defined conditions, but neuronal activity was well developed before CBF started to increase. Consequently, the absence of a rise in CBF does not exclude the presence of significant neuronal activity. The CBF increase in upper cortical layers preceded the rise in lower layers suggesting that vessels close to or at the brain surface are the first to react to neuronal activity. The activity-dependent rise in CBF was explained by postsynaptic activity in glutamatergic neurons.

Ancestral origins of the Machado-Joseph disease mutation: a worldwide haplotype study.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder originally described in families of Portuguese-Azorean ancestry. The cloning of the MJD1 gene allowed identification of the disease in many other populations, and MJD is now known to be the most common cause of dominant spinocerebellar ataxia. The hypothesis that its present world distribution could result from the spread of an original founder mutation has been raised, both at historical and molecular levels. In the present study, we tested this hypothesis by linkage-disequilibrium analysis of tightly linked polymorphisms and by haplotype comparison, in 249 families from different countries. We typed five microsatellite markers surrounding the MJD1 locus (D14S1015, D14S995, D14S973, D14S1016, and D14S977), and three intragenic single-base-pair polymorphisms (A(669)TG/G(669)TG, C(987)GG/G(987)GG, and TAA(1118)/TAC(1118)). The results show two different haplotypes, specific to the island of origin, in families of Azorean extraction. In families from mainland Portugal, both Azorean haplotypes can be found. The majority of the non-Portuguese families also share the same intragenic haplotype seen in the families coming from the island of Flores, but at least three other haplotypes were seen. These findings suggest two introductions of the mutation into the Portuguese population. Worldwide, the sharing of one intragenic haplotype by the majority of the families studied implies a founder mutation in MJD.

Nitric oxide synthase expression of oligodendrogliomas.

In the central nervous system, nitric oxide (NO) has a variety of biological functions including vasorelaxation and neurotransmission. The synthesis of NO is catalyzed by NO synthases (NOS) existing in 3 isoforms, neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). NO synthase has implications in the pathophysiology of primary glial brain tumors with enhanced expression of nNOS and eNOS in high-grade astrocytic tumors, WHO grades III and IV. Only minor groups of pure oligodendrogliomas have been investigated. The aim of the investigation was to study the expression of the 3 NOS isoforms in this genetically divergent group of primary gliomas and to correlate the findings with tumor grade and expression pattern for the major group of gliomas--the astrocytomas. We examined the NOS expression in 35 oligodendrogliomas, WHO grade II, and 7 anaplastic oligodendrogliomas, WHO grade III, by immunohistochemical methods using formalin-fixed paraffin-embedded material. We observed only a minor expression of nNOS and sparse expression of eNOS in the tumor cells, but a vivid expression of eNOS in the vascular endothelial cells in both the tumor and the surrounding tissue. The rich expression of eNOS in oligodendroglioma vessels independent of tumor grade may suggest that blood flow and angiogenesis in these richly vascularized tumors are modified by NO. Interestingly, enhanced expression of inducible NOS was observed in the oligodendroglial tumor cells in 19 of 35 oligodendrogliomas (54%) and in 2 of 7 anaplastic oligodendrogliomas (29%). This is diverging for iNOS expression in astroglial tumors and the data could be indicative of iNOS exerting anti-tumor activity which may protract the progression from low-grade oligodendrogliomas to more anaplastic types.

Nitric oxide synthase activity and expression in experimental diabetic neuropathy.

The changes of nitric oxide synthase (NOS) activity and expression in experimental diabetic neuropathy have not been examined. Increases in ganglia NOS might be similar to those that follow axotomy, whereas declines in endothelial NOS (eNOS) and immunological NOS (iNOS) might explain dysfunction of microvessels or macrophages. In this work, we studied NOS activity in lumbar dorsal root ganglia (DRG) of rats with both short- and long-term experimental streptozotocin-induced diabetes and correlated it with expression of each of the 3 NOS isoforms. NOS enzymatic activity in DRG increased after 12 months of diabetes. This increase, however, was not accompanied by an increase in neuronal NOS immunohistochemistry or mRNA. Immunohistochemical and RT-PCR studies did not identify changes of eNOS expression in 12-month sciatic nerves or DRG from diabetics. Two-month diabetic DRG had increased eNOS mRNA and there was novel eNOS labeling of capsular DRG and perineurial cells. iNOS mRNA levels were lower in diabetics at both time points in peripheral nerves but were unchanged in DRG. Diabetic ganglia showed an increase in NOS activity not explained by novel NOS isoform synthesis. The increases may compensate for NO "quenching" by endproducts of glycosylation. Declines in iNOS may indicate impaired macrophage function.

In vivo mechanisms of acetylcholine-induced vasodilation in rat sciatic nerve.

We examined the importance of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and neurogenic activity in agonist-induced vasodilation and baseline blood flow [i.e., nerve microvascular conductance (NMVC)] in rat sciatic nerve using laser Doppler flowmetry. Agonists were acetylcholine (ACh) and 3-morpholinosydnonimine (SIN-1). Vasodilation occurring despite NO synthase (NOS) and cyclooxygenase inhibition and showing dependence on K(+) channel activity was taken as being mediated by EDHF. NOS and cyclooxygenase inhibition with N(omega)-nitro-L-arginine (L-NNA) + indomethacin (Indo) revealed two phases of ACh-induced vasodilation: an initial, transient L-NNA + Indo-resistant vasodilation, peaking at 23 +/- 6 s and lasting 145 +/- 69 s, followed by sustained L-NNA + Indo-sensitive vasodilation. L-NNA alone did not affect sustained ACh-induced vasodilation but decreased baseline NMVC by 55%. In the presence of L-NNA + Indo, the K(+) channel blocker tetraethylammonium (TEA) inhibited transient ACh-induced vasodilation by 58% and reduced baseline NMVC by 25%. SIN-1-induced vasodilation increased fourfold in the presence of L-NNA, whereas the specific guanylyl cyclase inhibitor 1H-(1, 2, 4)oxadiazolo(4,3-alpha)quinoxalin-1-one abolished it. However, in homogenates of rat sciatic nerve, SIN-1-stimulated soluble guanylyl cyclase (sGC) activity was unaffected by L-NNA. TTX affected neither SIN-1- nor ACh-induced vasodilation. In conclusion, ACh-induced vasodilation consisted of two components, the first partially mediated by EDHF and the second by a vasodilatory prostanoid + NO. Baseline NMVC was dependent on NO and EDHF. Although L-NNA enhanced SIN-1-induced vasodilation, it had no effect on sGC-activity.

Diagnostic value of electrophysiological tests in patients with sciatica.

OBJECTIVES: To assess the diagnostic value of electrophysiological tests in patients with sciatica. MATERIALS AND METHODS: The diagnostic value of electrophysiological tests were evaluated in 25 patients with monoradicular sciatica. The electrophysiological study included dermatomal somatosensory evoked potentials, electromyography, F-wave latencies, H-reflexes and motor and sensory nerve conduction determinations. The results of the electrophysiological examinations were evaluated blindly, and the test results were analysed separately by a receiver operating characteristic (ROC) analysis. Furthermore, the 5 modalities were evaluated jointly and analysed by a decision-analytic regret function. RESULTS: A high predictive value was found for the H-reflex examination, but low for the other modalities. When the 5 modalities were evaluated jointly, a non-significant decrease in expected regret from the pre-test situation of 0.96 to a value of 0.93 in post-test situation was revealed. CONCLUSION: Electrophysiological testing is not sufficient as stand-alone examination in patients with sciatica.

Regulation of cerebral microcirculation--update.

The present symposium during Brain 99 was convened to explore the current aspects of the neural (extrinsic and intrinsic) and chemical control of the microvasculature in the brain with specific relevance to stimuli and rapid flow responses. N. Suzuki demonstrated the presence of neurokinin-1 receptors along the axons of vasoactive intestinal polypeptide-containing cerebrovascular parasympathetic nerves. Since the receptors were activated by substance P, calcitonin gene-related peptide and neurokinin released from coexisting sensory nerve fibers, the parasympathetic (vasodilating) fibers could effect rapid local flow increases. N. Suzuki, however, considered this as part of an elaborate defensive network protecting the brain from invasions by noxious substances. E. Hamel discussed the responses of the microvessels to neurotransmitters and suggested that nitric oxide (NO) released from intrinsic neurons may serve as a relay in the flow activation responses by intracerebral cholinergic fibers originating in the basal forebrain nuclei. D. Busija summarized a vasodilating system of activated N-methyl-D-asparate receptors located on neurons involving Ca influx-NO production, and activated ATP-sensitive potassium channels located in the vascular system. According to Busija, such interactions were disrupted during hypoxia and ischemia due to cyclooxygenase-derived superoxide anion. M. Lauritzen observed a 10 times larger increase in blood flow on stimulation of the climbing nerve as compared with that following the parallel nerve stimulation. The former transmitters are considered by him to be NO and K, and the latter NO and adenosine. Each speaker singled out NO as a common mediator for the microvasculature in the rapid local flow increases.

Temporal coupling between neuronal activity and blood flow in rat cerebellar cortex as indicated by field potential analysis.

1. Laser-Doppler flowmetry and extracellular recordings of field potentials were used to examine the temporal coupling between neuronal activity and increases in cerebellar blood flow (CeBF). 2. Climbing fibre-evoked increases in CeBF were dependent on stimulus duration, indicating that increases in CeBF reflected a time integral in neuronal activity. The simplest way to represent neuronal activity over time was to obtain a running summation of evoked field potential amplitudes (runSigmaFP). RunSigmaFP was calculated for each stimulus protocol and compared with the time course of the CeBF responses to demonstrate coupling between nerve cell activity and CeBF. 3. In the climbing fibre system, the amplitude and time course of CeBF were in agreement with the calculated postsynaptic runSigmaFP (2-20 Hz for 60 s). This suggested coupling between CeBF and neuronal activity in this excitatory, monosynaptic, afferent-input system under these conditions. There was no correlation between runSigmaFP and CeBF during prolonged stimulation. 4. Parallel fibre-evoked increases in CeBF correlated with runSigmaFP of pre- and postsynaptic potentials (2-15 Hz for 60 s). At higher stimulation frequencies and during longer-lasting stimulation the time course and amplitudes of CeBF responses correlated with runSigmaFP of presynaptic, but not postsynaptic potentials. This suggested a more complex relationship in this mixed inhibitory-excitatory, disynaptic, afferent-input system. 5. This study has demonstrated temporal coupling between neuronal activity and CeBF in the monosynaptic, excitatory climbing-fibre system. In the mixed mono- and disynaptic parallel fibre system, temporal coupling was most clearly observed at low stimulation frequencies. We propose that appropriate modelling of electrophysiological data is needed to document functional coupling of neuronal activity and blood flow.

Scanning laser-Doppler flowmetry of rat cerebral circulation during cortical spreading depression.

Scanning laser-Doppler flowmetry (SLDF) generates two-dimensional images of blood flow. This study compared SLDF to conventional laser-Doppler flowmetry (LDF) in the cerebral circulation. Test stimuli were episodes of cortical spreading depression (CSD) elicited in brains of halothane anaesthetised rats (n = 9). The LDF instrument used two wavelengths of laser light to record relative changes of cerebral blood flow (CBF) up to an approximate depth of 250 microm (543 nm) and 500 microm (780 nm). Under resting conditions, SLDF images showed a heterogeneous pattern of flow in pial vessels with high flow rates in arterioles, and lower rates in venules and small vessels (<30 microm). Arterioles constituted about 6%, venules 12% and small vessels 2% of the image area, while approximately 80% were background with a laser-Doppler signal corresponding to zero calibration. During CSD, the relative increase of area was largest for small vessels and less for venules and arterioles. Similar changes were observed for blood flow in the three vessel structures. For both wavelengths of LDF, flow changes correlated with SLDF (r approximately 0.7). In conclusion, SLDF provides images of flow in pial vessels and capillaries at, or just beneath the cortical surface. SLDF and LDF are complementary, but cannot substitute for one another as they measure flow in different layers of the cortex.

Functional recruitment of red blood cells to rat brain microcirculation accompanying increased neuronal activity in cerebellar cortex.

Scanning laser-Doppler flowmetry (SLDF) combines laser-Doppler flowmetry and laser scanning to provide images of cerebral blood flow (CBF) with high spatial and temporal resolution. We investigated the contribution of single vascular elements to the local increase of CBF accompanying increased neuronal activity in halothane-anesthetized rats. CBF was examined in the cerebellar cortex under control conditions and in response to electrical stimulation of parallel and climbing fibers. At rest, arterioles contributed 9%, venules 11-13% and small vessels (< 20 microm) 8-14%, while the background constituted 64-72% of the total SLDF signal. During activation the background signal decreased to 55-60% while the signal from arterioles increased to 11-12%, from venules to 14-15% and from small vessels to 14-19%. The signal increase in small vessels that did not give any laser-Doppler signal at rest was due to functional recruitment of red blood cells to the capillary bed. We conclude that functional recruitment may be an integral part of the hemodynamic response accompanying neuronal activity.