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Results for “Microvessels”

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PubMed1996

Optimized microvessel density analysis improves prediction of cancer stage from prostate needle biopsies.

OBJECTIVES: Clinical staging of prostate cancer is inaccurate, often with significant upstaging on final pathologic review. We previously demonstrated the ability to predict extraprostatic extension of cancer by use of the Gleason score and serum prostate-specific antigen (PSA) measurements. Herein we present an interim analysis of data from an ongoing multi-institutional study to determine the predictive power of an enhancement of microvessel density analysis in combination with Gleason score and serum PSA to predict extraprostatic extension. METHODS: We evaluated a total of 186 randomly selected biopsy samples and matched totally embedded radical prostatectomy samples with preoperative PSA concentrations and patient demographics. Gleason score and optimized microvessel density (OMVD) were determined from the needle biopsy samples; pathologic stage was verified by independent review of the radical prostatectomy samples. An automated digital image analysis system measured microvessel morphology and calculated the OMVD in the biopsy samples (Biostage; Bard Diagnostic Sciences, Seattle, Wash). RESULTS: Prediction of extraprostatic extension was increased significantly when OMVD analysis was added to Gleason score and serum PSA concentration (P = 0.003). CONCLUSIONS: Optimized microvessel density analysis significantly increases the ability to predict extraprostatic extension of cancer preoperatively when combined with Gleason score and serum PSA concentration. This method appears to be a useful tool that can assist with treatment decisions in selected patients.

Aged↗

PubMed1999

Role of microvessel density in predicting recurrence in pathologic Stage T3 prostatic adenocarcinoma.

OBJECTIVES: Extraprostatic extension of prostatic adenocarcinoma (pathologic Stage T3) increases the risk of recurrence after radical prostatectomy compared with organ-confined prostate cancer. Use of microvessel density in predicting cancer recurrence in Stage pT3 cancer is poorly understood. We evaluated known predictors of recurrence, including Gleason grade, preoperative serum prostate-specific antigen (PSA), DNA ploidy, seminal vesicle involvement, and surgical margin status in comparison with optimized microvessel density (OMVD) and area-weighted microvessel density (AWMVD) in patients with Stage pT3 prostate cancer. METHODS: Between 1987 and 1989, 290 previously untreated patients underwent radical prostatectomy and were found to have pathologic Stage T3 adenocarcinoma. No patient received adjuvant therapy. Embedded prostatectomy specimens from 211 patients with sufficient tissue for immunohistochemical staining with factor VIII-related antigen were studied by computer-assisted digital image analysis for OMVD and AWMVD. The correlation of Gleason grade, preoperative PSA, DNA ploidy, seminal vesicle involvement, surgical margin positivity, OMVD, and AWMVD with clinical or biochemical failure was assessed using the Cox proportional hazards model. Biochemical failure was defined as a postoperative increase in PSA greater than 0.2 ng/mL, and clinical failure was defined as a positive biopsy or metastasis on bone scan. RESULTS: The mean follow-up +/- SD for all patients was 7.1 +/- 1.8 years, with 43 deaths (9 due to prostate cancer) and 124 cases of clinical and/or biochemical recurrence. The mean OMVD was 65.0 +/- 17.3, and the mean AWMVD was 8.2 +/- 5.3. OMVD and AWMVD were not predictors of cancer recurrence or significantly associated with DNA ploidy or preoperative PSA. AWMVD was associated with Gleason grade (P = 0.003). The estimated relative risk (adjusted for other cancer variables) of clinical and biochemical recurrence associated with a change in OMVD from the 25th percentile (53.5) to the 75th percentile (75.4) was 1.14 (95% confidence interval 0.92 to 1.42). The estimated relative risk (adjusted) of clinical and biochemical recurrence associated with a change in AWMVD from the 25th percentile (4.8) to the 75th percentile (10.4) was 1.17 (95% confidence interval 0.97 to 1.42). Gleason grade, preoperative PSA, DNA ploidy, and seminal vesicle involvement were predictors of clinical and/or biochemical recurrence in univariate and multivariate analyses. CONCLUSIONS: Microvessel density, assessed by OMVD and AWMVD, did not predict recurrence in patients with pathologic Stage T3 adenocarcinoma of the prostate (TNM Stage T3N0M0). DNA ploidy, Gleason grade, preoperative PSA, and seminal vesicle involvement remained the best predictors of clinical and/or biochemical recurrence in this group of patients.

Adenocarcinoma↗

PubMedDate not supplied

Ultrastructural and permeability features of microvessels in the hippocampus, cerebellum and pons of senescence-accelerated mice (SAM).

We previously reported that the accumulation of blood-borne radiolabelled serum albumin in brain parenchyma increased with aging, especially in senescence-accelerated mice (SAMP8), which showed age-related deficits in learning and memory. In this study, in order to examine morphological events related to the age-related increase of the brain accumulation of serum albumin, the transvascular passage of blood-borne horseradish peroxidase (HRP) and ultrastructural features of microvessels were examined in the hippocampus, cerebellum and pons of SAMP8 and SAMR1 (control) mice. Ultrastructural examination of the hippocampus showed that the staining for HRP was occasionally spreading throughout the parajunctional cytoplasm of the endothelial cell of aged SAMP8 mice, but not in young SAMP8 mice nor in SAMR1 mice. The number of vessels showing the staining reaction for HRP in the parajunctional cytoplasm of the endothelial cells in aged SAMP8 mice increased significantly compared with that in the others. Electron microscopic morphometry showed that there were no significant differences among the number of HRP-positive vesicles per unit area of the endothelial cell cytoplasm in young and old mice of both strains. The staining reaction for HRP was not seen in the basal lamina of microvessels and the perivascular neuropil in all mice examined. Perivascular lipofuscin-like granules and collagen deposits, swelling of astroglial perivascular endfeet and perivascular cells containing foamy, lipid-like droplets were frequently found in several brain regions of aged SAMP8 mice. The perivascular cells with a few lipid-like droplets and more electron-homogeneous lysosomes were occasionally seen in SAMR1 and young SAMP8, while the other findings were scarcely observed in SAMR1 and young SAMP8 mice. These findings suggest that the blood-brain barrier to HRP was preserved in microvessels in three brain regions of SAM mice but the blood microvessels showed some age-related ultrastructural alterations in SAMP8 brains. Uncontrolled passage of HRP through the parajunctional cytoplasm of the endothelial cells may partly contribute to the age-related increase of accumulation of serum albumin in SAMP8 brains.

Aging↗

PubMed2001

Aquaporin subtypes in rat cerebral microvessels.

We investigated the expression of aquaporin (AQP) subtypes in the rat cerebral microvessels by reverse transcription-polymerase chain reaction, immunoblotting and immunohistochemistry. mRNA for AQP4, but not for AQP1, 2, 3 or 5, was detected in the microvessels. Immunoblot analysis showed that AQP4 protein was detected as a 30 kDa band with higher molecular weight bands. Immunohistochemical staining showed that AQP4 was located on cell surface of the cerebral microvessels. These results suggest that AQP4 in the cerebral microvessels is involved in the regulation of water transport between blood and brain.

Animals↗

PubMed1998

Protein kinase C-zeta activity but not level is decreased in Alzheimer's disease microvessels.

While there is considerable evidence demonstrating altered activity of the major isoforms of protein kinase C (PKC) in the vasculature and neurons of Alzheimer disease (AD) brains, little is known about the activity and/or levels of the atypical PKC isoforms. The objective of this study is to compare PKC-zeta activity and level in cerebral microvessels isolated from AD brains with microvessels from the brains of nondemented age-matched controls. Measurements of the kinase activity reveals that the PKC-zeta activity is significantly (P < 0.01) lower in AD brain microvessels compared with vessels from control brain. Despite this decrease in enzyme activity, the level of PKC-zeta, assessed by Western blot, is significantly (P < 0.01) elevated in AD microvessels. These data demonstrate significant and divergent changes in the PKC-zeta activity and level in the microcirculation of the AD brain and suggest that aberrant regulation of microvascular PKC-zeta could contribute to the abnormal signaling mechanisms at the blood-brain barrier in the AD brain.

Aged↗

PubMed1998

Endothelial expression of the 5-hydroxytryptamine1B antimigraine drug receptor in rat and human brain microvessels.

In addition to triggering vasoconstriction of peripheral blood vessels, which led to its discovery as a circulating neurohormone 50 years ago, serotonin (5-hydroxytryptamine) acts as a neurotransmitter/ modulator in the central nervous system and regulates local cerebral blood flow and vascular permeability through direct and indirect effects on intraparenchymal microvessels. Among the various 5-hydroxytryptamine receptors which mediate these effects, particular attention has been paid to the 5-hydroxytryptamine1B and 5-hydroxytryptamine1D subtypes, as the preferred targets of modern antimigraine agents. Immunoelectron microscopic labeling of the 5-hydroxytryptamine1B receptor in rat brain parenchyma has revealed a distinct localization to the endothelium of microvessels, which was predominantly cytoplasmic as opposed to membrane-bound, contrary to that on preterminal unmyelinated axons [Riad et al. (1997) Soc. Neurosci. Abstr. 23, 1214]. Similar observations have now been made in human cortical tissue, in which the expected localization of the vascular 5-hydroxytryptamine1B receptor to periarteriolar myocytes was also confirmed. Such a dual localization in human brain microvessels suggests that the 5-hydroxytryptamine1B receptor might mediate opposite effects, vasodilatory and contractile, depending upon its activation by circulating or centrally released 5-hydroxytryptamine. It raises new possibilities as regards 5-hydroxytryptamine effects on human brain microvessels in health and disease, and notably the triggering of migraine headache.

Animals↗

PubMed1999

Regional cholinergic denervation of cortical microvessels and nitric oxide synthase-containing neurons in Alzheimer's disease.

In the present study, we investigated in the human cerebral cortex whether, as in the rat, basal forebrain cholinergic neurons innervate cortical microvessels and nitric oxide synthase-containing neurons and, further, we compared the status of this innervation between aged controls and neuropathologically confirmed cases of Alzheimer's disease. Using immunocytochemistry of choline acetyltransferase coupled to reduced nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry, we show in young human subjects the presence of a cholinergic input to the cortical microcirculation, and of numerous perisomatic and peridendritic contacts between cholinergic nerve terminals and reduced nicotinamide adenine dinucleotide phosphate-diaphorase neurons. A regional cholinergic denervation of both cortical microvessels and reduced nicotinamide adenine dinucleotide phosphate-diaphorase neurons was found in Alzheimer's disease patients as compared to aged controls, and it paralleled the loss of total cholinergic nerve terminals in the corresponding areas of the cerebral cortex. The vascular denervation was more severe in the temporal (77%, P < 0.05) than in the frontal (48%, not significant) cortex, and the reduced nicotinamide adenine dinucleotide phosphate-diaphorase intracortical neurons were similarly deprived of their cholinergic input (P < 0.01) in both regions. Interestingly, a significant increase in luminal diameter (48%, P < 0.01) and area (> 160%, P < 0.01) of perfused microvessels was found in Alzheimer's tissues, possibly a consequence of both loss of neurogenic input and structural changes in blood vessel walls. The data indicate that intracortical microvessels and nitric oxide neurons in Alzheimer's disease are deprived of a cholinergic neurogenic control, a situation which is likely to result in a compromised ability to adapt cortical perfusion to neuronal activation during functional tasks related to cognition, arousal and attention. We conclude that such deficits in neurovascular regulation are likely to be an important pathogenic factor underlying cerebral blood flow dysfunctions in Alzheimer's disease.

Adult↗

PubMed2003

Correlation between the arthroscopic diagnosis of synovitis and microvessel density in synovial tissues in patients with internal derangement of the temporomandibular joint.

OBJECTIVE: To elucidate the correlation between the arthroscopic diagnosis of synovitis and microvessel density in synovial tissues in patients with internal derangement of the temporomandibular joint (TMJ). STUDY DESIGN: Forty-three joints in 41 patients with internal derangement were examined and biopsies taken. Microvessel density was evaluated using the immunohistochemical method for CD 34 antibody. Arthroscopically diagnosed synovitis was evaluated according to Murakami's criteria. RESULTS: In patients with internal derangement, arthroscopically diagnosed synovitis scores averaged 5.2+/-2.0, according to Murakami et al. (1991). Small to large blood vessels were observed clearly with CD 34 stain. The mean microvessel density was 22.7+/-15.6 per two high power fields (magnification x200). Synovitis scores correlated significantly with microvessel density (p=0.002, r=0.43). CONCLUSION: Synovitis evaluated using Murakami's scores correlated well with the number of blood vessels in synovial tissues in patients with internal derangement of the TMJ. This demonstrates that synovitis is linked to inflammation-related blood vessel density of the synovial tissues.

Adolescent↗

PubMed2002

Recovery of radial PO(2) profiles from phosphorescence quenching measurements in microvessels.

Work by previous investigators has indicated that a substantial amount of oxygen diffuses from the precapillary circulation. These losses imply that there should be radial gradients of oxygen tension (PO(2)) in arterioles, leading to a non-uniform distribution of oxygen within these microvessels. We have employed the phosphorescence quenching method to measure oxygen, allowing us to evaluate the heterogeneity of PO(2) inside short segments of microvessels. The phosphorescence decay curve contains information about the distribution of oxygen within the excited volume and the distribution can be represented as a histogram, by decomposing the decay curve into several components with weights proportional to the volume fraction of plasma with different PO(2), under the condition of a high signal-to-noise ratio. Furthermore, the histogram can be converted into a radial profile of PO(2), based on the assumptions of a circular vascular lumen, axisymmetric distribution of oxygen and monotonic PO(2) profile. Albumin-bound Pd-porphyrin phosphor was infused into the circulation of hamsters and excited by flash illumination at 10 Hz, with a square region of excitation light just covering the entire lumen, (i.e. width of region equaled luminal diameter) of microvessels in the hamster mesentery. A set of 50 curves (5 s of data) was averaged to obtain a decay curve with low noise. Curves were analyzed with the above histogram procedure, and this analysis allowed us to distinguish between PO(2) values originating from intra and extravascular subvolumes. The intravascular PO(2) in these microvessels was very heterogeneous, which could be explained by the existence of significant radial PO(2) gradients. The radial PO(2) gradients were estimated to be approximately 1 mmHg/microm.

Animals↗

PubMed1997

Influence of investigator experience and microscopic field size on microvessel density in node-negative breast carcinoma.

In this study on the determination of intratumoral microvessel density (MVD) in breast cancer, we have investigated the influence of the observer experience and the microscopic field size. We have used the sample set reported on earlier in the J Natl Cancer Inst 87: 1797-1798, 1995. This case-control study has shown a positive association of high MVD and unfavorable outcome when comparing node-negative pT1-2 breast carcinoma (NNBC) patients with a disease-free period of over ten years with those with an early distant relapse. Tumor sections of both outcome groups (favorable: n = 19; unfavorable: n = 19) were immunostained for factor VIII related-antigen (FVIII r-Ag). Microvessels were counted in the areas of most intense vascularization ('hot spots'), both at magnification x 200 (field size of 0.61 square mm) and x 400 (field size of 0.15 square mm), by one inexperienced and three experienced observers. Microphotographs of individual vascular hot spots were analyzed using overlays resembling the two field sizes. The main results obtained are: i) a confirmation of the prognostic value of microvessel density in the case-control sample set (n = 38) was established by all experienced but not by the unexperienced investigator; ii) both at x 200 and x 400 magnification, angiogenesis quantification in vascular hot spots contained prognostic information. The results of this study indicate that the selection of vascular hot spots in tumor sections immunostained for an antigen expressed on endothelial cells is more prone to inter-observer variability and more dependent on training than the counting of the microvessels within predefined hot spots itself. The microscopic magnification and resulting field size do not influence the prognostic significance of MVD in NNBC. This information validates the development of more objective methods of measuring the amount of angiogenesis within malignant tissue. This will allow more accurate implementation of the angiogenesis parameter in multiparametric and prospective prognostic factor studies in NNBC.

Adenocarcinoma↗

PubMed1997

Distribution of stromelysin-3 mRNA transcripts and microvessels in human breast carcinomas.

Several proteinases, implicated in tumor invasion, are expressed in fibroblastic cells surrounding neoplastic cells, and are believed to be induced by paracrine stimulation. Such stimulation, by the local release of angiogenic factors, is also responsible for the induction of new capillary blood vessels, a crucial aspect of tumor growth and metastasis. We have here compared the expression of a matrix metalloproteinase, stromelysin-3 (ST3), with the distribution of tumor microvessels in invasive breast carcinomas. The highest level of ST3 mRNA in each tumor was recorded and compared to the highest microvessel density. No correlation between these two parameters was observed by analysis of 63 tumors. Detailed examination of 19 individual tumors did not reveal any correlation between the distribution of ST3 mRNA and microvessels. In the material studied here, ST3 expression was observed to correlate with long-term survival of the patients, whereas microvessel density did not correlate.

Breast Neoplasms↗

PubMed1999

The methodology of quantitation of microvessel density and prognostic value of neovascularization associated with long-term survival in Japanese patients with breast cancer.

The present study updates results on methodology of quantitation of tumor neovascularization and those on the prognostic value of microvessel density (MVD) in breast cancer tissue previously published in the World J. Surg. 21: 49-56, 1997. The follow-up period of observation of the series was extended to 20 years, and new biological indicators (i.e., proliferating cell nuclear antigen (PCNA), c-erbB-2, and p53) were included in the analysis. There were 109 patients with primary breast cancer, from 1971 to 1979, followed up for a median of 14 years (range, 1-20). A representative median longitudinal section of each breast tumor was immunohistochemically stained with factor VIII-related antigen and analyzed. The three methods of identifying MVD were: (1) average microvessel count (AMC)/mm2, (2) central microvessel count (CMC)/mm2, and (3) highest microvessel count (HMC)/mm2. Thirty-one patients (28.4%) died of breast cancer. There was a relationship between MVD and peritumor blood vessel invasion (AMC: p = 0.0114, CMC: p = 0.0319, and HMC: p = 0.0009). However, there was no relationship between MVD and other factors. Univariate analysis showed that node status (p < 0.0001), histological grade (p < 0.0001), clinical tumor size (T) (p = 0.0002), PCNA (p = 0.0033), p53 (p = 0.0043), mitotic grade (p = 0.0092), AMC (p = 0.0214), and peritumor lymphatic vessel invasion (p = 0.0467) were significantly predictive of overall survival. HMC was borderline significant (p = 0.0702), while CMC and c-erbB-2 were not significant. Multivariate analysis showed that T (p = 0.0005), node status (p = 0.0053), and AMC (p = 0.0485) were independent factors, but neither CMC nor HMC was independent. AMC, a significant independent prognostic factor, might be a better method than the others for evaluating angiogenesis, but further and larger studies are warranted.

Adult↗

PubMed1999

Pediatric medulloblastoma: prognostic value of p53, bcl-2, Mib-1, and microvessel density.

The aim of this study was to retrospectively assess the prognostic value of p53 and bcl-2 protein expression, cell proliferation index (Mib-1 index), and tumor microvessel density (factor VIII-related antigen) in pediatric medulloblastoma patients. Tumor specimens of 55 patients (age 2-18 years) with medulloblastoma treated with a curative intent between 1972 and 1991 were studied. Slides of paraffin embedded tissue were stained with monoclonal antibodies (mAb) and examined under high power light microscopy for the presence of immunoreactivity. Microvessel density was scored both in the area of most intense staining ('Angio-max') and in 3 additional randomly selected areas. The sum of these 4 scores was termed 'Angio-total'. 'Angio-max' and 'Angio-total' were evaluated separately by two independent investigators to assess reproducibility. None of the parameters studied, i.e. p53 or bcl-2 expression, Mib-1 index or microvessel density scores were associated with patient survival. Microvessel scores between observers were significantly but weakly correlated, with correlation coefficients (r) < 0.5 for both 'Angio-max' and 'Angio-total'. Leptomeningeal spread at diagnosis was the only independent factor associated with a poor survival (p = 0.003). There was no association of leptomeningeal metastasis with any of the biological markers tested in this study.

Adolescent↗

PubMed1998

Gamma-glutamyl transpeptidase does not act as a cystine transporter in brain microvessels.

Gamma-glutamyl transpeptidase (GGTP) is highly enriched in blood-brain barrier (BBB) microvessels. According to the most cited hypothesis its functional role is amino acid transport across the BBB. To test this hypothesis the influence of GGTP inhibition on cystine uptake was measured in isolated brain microvessels. Adult porcine brain microvessels were enzymatically isolated, resulting in an enrichment of GGTP from 3 to 85 U/mg protein. The inhibitors 0.1 mM AT-125 combined with 20 mM hippurate reduced the GGPT enzyme activity by more than 98%. However this inhibition did not influence the uptake of [35S]-cystine, which is the substrate with the highest affinity in the GGTP-reaction. Instead increased glutathione (GSH) levels and elevated [35S] release were found. These results show that GGTP does not mediate the transport of cystine into brain microvessels in vitro and suggest that GGTP plays a role in cellular GSH metabolism.

Amino Acids↗

PubMed1998

Arecoline stimulation of radiolabeled arachidonate incorporation from plasma into brain microvessels of awake rat.

The cholinergic agonist, arecoline, was used to examine the effects of cholinergic stimulation upon incorporation of radiolabeled arachidonic acid from blood into cerebral microvessels of awake rats. Animals received a single i.p. injection of arecoline (1 mg/kg) followed 3 to 5 minutes later by a 5 minute intravenous infusion of [1-14C]arachidonic acid (AA) (170 microCi/kg) via the femoral vein. Timed arterial blood samples were collected over 20 minutes following the start of infusion, after which the animal was killed, and the brain was removed. The incorporation coefficient k* for [1-14C]AA was approximately 2-fold higher in microvessels isolated from arecoline-injected than from sham-injected animals. The data demonstrate in an in vivo paradigm, that activation of cholinergic pathways within the rat CNS stimulates arachidonic acid turnover in cerebral microvessels. This suggests a direct involvement of this fatty acid in second messenger function within microvessel endothelial cells and possibly attached pericytes.

Animals↗

PubMed1998

Independent prognostic importance of microvessel density in endometrial carcinoma.

Angiogenesis is thought to be an important factor for tumour growth and metastatic spread, and microvessel counts may provide useful prognostic information for several tumour types. To investigate the prognostic impact of angiogenesis in endometrial carcinoma patients, the intratumour microvessel density, which was determined immunohistochemically, has been related to survival. Sixty patients with endometrial carcinoma with long (median 19 years) and complete follow-up have been studied. Patients with increased mean microvessel density (MVDmean > 68 mm2) had a significantly shorter 5-year survival compared with the rest (57% vs 90%, P = 0.004). In multivariate survival analyses, MVDmean had an independent prognostic impact (P = 0.03) when FIGO stage, histological type, histological grade as well as nuclear p53 protein expression was adjusted for. These findings indicate that intratumour microvessel density may contribute additional prognostic information to that obtained from the known risk factors and may be helpful in identifying endometrial carcinoma patients at high risk for disease progression.

Adult↗

PubMed1985

Specific ouabain binding to brain microvessels and choroid plexus.

The energy-dependent transport of ions across the blood-brain barrier and the blood-cerebrospinal fluid barrier by Na+, K+-ATPase is credited with an important role in brain homeostasis. In this study, we have assessed the relative enrichment of Na+, K+-ATPase in regional brain capillary preparations and in the choroid plexus by the quantitative determination of the cardiac glycoside binding sites in these preparations using [3H]ouabain as a ligand. We find that ouabain binds specifically to brain microvessels of the rat and the pig and to the choroid plexus of the pig in a saturable manner. The maximum density of ouabain binding sites in brain microvessels of both species is about one-fourth that of the crude membranes of the cerebrum and cerebellum. The density of ouabain binding sites in the pig choroid plexus is intermediate between that of the brain and brain microvessels. We do not find regional differences in ouabain binding to membrane fractions of the cerebrum and cerebellum, nor any significant differences in ouabain binding to cerebral and cerebellar microvessels. These findings provide quantitative estimates of Na+, K+-ATPase in brain capillaries and choroid plexus.

Animals↗

PubMed1988

Absence of N-methyl-D-aspartate receptors on ovine cerebral microvessels.

Radioreceptor methods were used to quantitate the N-methyl-D-aspartate (NMDA) receptor-complex of ovine cerebral microvessels and cerebral gray matter. Specific binding of D[3H]2-amino-5-phosphono-pentanoate and [3H]1-[1-(2-thienyl)cyclohexyl]piperidine, ligands for the NMDA primary acceptor site and ionophore, respectively, was found in cerebral gray matter but was not detectable in membranes prepared from brain microvessels enriched in capillaries. Sigma receptors, another locus of action for phencyclidine congeners, were also not present on microvessels but were found in cortical homogenates. On the other hand, cerebral microvessels and gray matter contained significant numbers of beta-adrenoceptors. Our results indicate the NMDA receptors and NMDA antagonists are unlikely to regulate the function of the cerebral microvasculature.

Animals↗