Biomedical subjects

Rui Li

Publications and source records attributed to Rui Li.

At least 91 records · Page 5Linked to original sources

PubMed2005

[Effects of Bacillus Calmette-Guerin vaccination on immune functional development of splenic T cell in neonatal mice].

OBJECTIVE: Almost every neonate receives Bacillus Calmette-Guerin (BCG) vaccination in China. The authors' previous study showed that BCG promoted cord blood monocyte-derived dendritic cells maturation and induced high level of interleukin (IL)-10, medium level of interferon (IFN)-gamma, but low level of IL-4 production by cord naive T cells. The experiments in the present study were designed to explore the effects of neonatal BCG vaccination on immune functional development of splenic T cells in mice in vivo. METHODS: Neonatal BALB/c mice were inoculated with BCG intraperiotoneally. Four weeks later, spleen cells of mice were isolated and surface molecular markers of CD4, CD25 and CD44 and intracellular IFN-gamma, IL-10, and IL-4 in CD3(+) T cells were detected by flow cytometry. Furthermore, mRNA expression of transcription factor T-bet, Foxp3 and GATA-3 were analyzed by RT-PCR. RESULTS: The percentage of total CD4(+) T cells decreased [(23.50 +/- 2.59)% vs. (47.38 +/- 10.41)%, P < 0.01] but the percentage of CD25(+) [(24.92 +/- 2.74)% vs. (20.27 +/- 2.85)%, P < 0.05] and CD44(+) [(89.29 +/- 2.56)% vs. (82.98 +/- 5.51)%, P < 0.05] T cells in CD4(+) T cells was higher in BCG-vaccinated mice than that in controls. Meanwhile, the percentage of IFN-gamma positive [(6.52 +/- 2.40)% vs. (3.13 +/- 2.03)%, P < 0.05] and IL-10 positive [(14.81 +/- 3.65)% vs. (10.90 +/- 1.61)%, P < 0.05] but not IL-4 positive [(1.17 +/- 0.46)% vs (1.51 +/- 0.75)%, P > 0.05] cells in CD3(+) T cells of BCG-vaccinated mice was significantly higher than that of non-BCG-vaccinated mice. In comparison with BCG-naive mice, T-bet was significantly high in BCG-vaccinated mice [T-bet/beta-actin 0.44 +/- 0.11 vs. 0.28 +/- 0.06, P < 0.05], but there was no significant difference in GATA-3 [GATA-3/beta-actin 0.46 +/- 0.08 vs. 0.50 +/- 0.10,P > 0.05] and Foxp3 [Foxp3/beta-actin vs. 0.27 +/- 0.11 and 0.30 +/- 0.16, P > 0.05] mRNA expression between the two groups. CONCLUSION: Neonatal BCG vaccination could induce strong Th1 but weak Th2 response as reported previously. Though neonatal BCG vaccination was not capable of inducing CD4(+)CD25(+) regulatory T cell response with Foxp3 expression, it caused increase of IL-10(+) CD3(+) cells which might represent some regulatory T cells producing IL-10.

Animals↗

PubMed2005

[The outcome analysis of different treatment regimens in 206 patients with multiple myeloma].

OBJECTIVE: To analyse the outcome of different regimens for the treatment of patients with multiple myeloma (MM). METHODS: Response rate, median survival time and overall survival rate of 206 MM patients treated with different protocols were retrospectively analysed. RESULT: The median survival time, 3- and 5-year overall survival (OS) of 200 MM patients treated with conventional therapy were 30.5 months, 32.0% and 15.8%, respectively. The total response rate and complete response (CR) rate of 195 patients treated with MP regimen and combination chemotherapy (CCT) were 45.6% and 14.9%, respectively. The response rates were higher for the patients treated with CCT than for those treated with MP (50.3% versus 30.4%, P < 0.05). The median survival time, 3- and 5- year OS in MP versus CCT group were 30.0 versus 30.5 months, 22.0% versus 35.0%, 13.2% versus 16.7%, respectively, but all of them have no statistical difference. Compared with those without IFN alpha maintenance therapy, patients received IFN alpha therapy showed a higher response rate (34.4% versus 53.6%, P < 0.05) and a longer median survival time (27 versus 52 months, P < 0.01). The total response in patients received thalidomide was 65.5%. Of the 6 patients received hematopoietic stem cell transplantation (HSCT), 5 remained alive in CR or PR with a mean survival time of (73.0 +/- 12.5) months. CONCLUSIONS: CCT yields higher response rates, but not longer survival time than MP does for the treatment of MM. The response rate as well as the overall survival rate increased when IFN alpha was used as maintenance therapy. Thalidomide can improve response rate as well. HSCT could prolong survival time in patients aged < 60 years with good status.

Adult↗

PubMed2005

[A meta-analysis of treatment of infantile diarrhea with bifid triple viable bacterial tablet].

OBJECTIVE: To assess the efficacy and safety of bifid triple viable bacterial tablet in treatment of infantile diarrhea. METHODS: According to the requirements of Cochrane systematic review, a thorough literature search was performed among Chinese Digital Hospital Library (www.chkd.cnki.net) and Chinese Biomedical Literature Disk Database (CBMdisk). A meta analysis was performed on a total of 1326 patients involved in 12 papers which met the inclusion criteria. RESULTS: Publication bias analysis showed that the funnel plot was symmetrical. Test for heterogeneity showed that the groups treated with bifid triple viable bacterial tablet and antibiotics or anti-viral agents or placebo control had clinical homogeneity and statistical homogeneity (P = 0.66, 0.67, 0.85, respectively, I(2) = 0%), which allowed to use fixed effect model analysis. The bifid triple viable bacterial tablet and Smecta did not have statistical homogeneity (P = 0.02, I(2) = 70.9%), therefore random effect model analysis was applied. Incorporation analysis showed that in comparison of the bifid triple viable bacterial tablet versus antibiotics or anti-viral agents or placebo control, the odds ratios were 5.34, 4.74 and 6.43, respectively, and 95% CIs were [2.81, 10.16], [2.47, 9.09], and [2.61, 15.83], on test for overall effect, Z = 5.11, 4.67 and 4.04, P < 0.00001. In the forest plot the 95% CI horizontal line of incorporation odds ratio droped to the right side of the vertical line indicating the border of effectiveness. However, no statistically significant difference was found between bifid triple viable bacterial tablet and Smecta. CONCLUSION: The clinical evidences available so far indicated that treatment of infantile diarrhea with bifid triple viable bacterial tablet is safe and effective although rigorously designed large sample size randomized double blind clinical trials are required to further demonstrate and support the conclusion.

Administration, Oral↗

PubMed2005

[Research on the Cun-Guan-Chi Pulse Detecting System].

The paper introduces the designing concept of the Cun-Guan-Chi Pulse Detecting System and its basic principles, and structural features. The system comprises 3 independent pressure sensors with same design parameters. It provides a scientific and quantitative method of detecting the pulses, which tallies well with the diagnostic method of the traditional Chinese medicine.

Biosensing Techniques↗

PubMed2005

[The in situ analysis of cytokine mRNA expression in immunological microenvironment about non-small cell lung cancer].

AIM: Using Non-small cell lung cancer (NSCLC) as subject, to explore the characteristics of immune response in immunological microenvironment at the tumor site and its effect on anti-tumor immunity. METHODS: Using in situ hybridization (ISH), the expressions of IL-2, INF-gamma, IL-12 (p40), IL-18, IL-4, IL-10, TGF-beta1, IL-1, IL-3, IL-8, GM-CSF, TNF-alpha and TGF-alpha mRNAs in lymphocytes and tumor cells from five fresh pleural effusion samples and 18 tumor tissue samples of NSCLC patients were detected by in situ hybridization with digoxin end-labeled oligonucleotide probe, using 5 tuberculous pleurisy patients as control. RESULTS: In pleural effusion and tumor tissue of NSCLC patients, the expression levels of IL-4, IL-10, TGF-alpha, and TGF-beta1 mRNAs were significantly higher than those of IL-2, IL-12, IL-18 and INF-gamma mRNAs. In contrast, the analysis of tuberculous pleural effusion samples revealed lower levels of above-mentioned cytokine mRNA. There was no significant difference among expression levels of these cytokine mRNAs. CONCLUSION: The expressions of type II cytokine mRNAs and immunosuppressive cytokine mRNAs in pleural effusion and tumor tissue of NSCLC patients occupied a dominant position, suggesting that the immunological microenvironment about tumor be in an immunosuppressive state. The present study has contributed to a better understanding the mechanisms of tumor escape and provides important experimental basis for working out the scheme for an effective immunomodulatory treatment of NSCLC patients.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

(-)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury.

Microglial activation is believed to play a pivotal role in the selective neuronal injury associated with several neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease. We provide evidence that (-)-epigallocatechin gallate (EGCG), a major monomer of green tea polyphenols, potently inhibits lipopolysaccharide (LPS)-activated microglial secretion of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) through the down-regulation of inducible NO synthase and TNF-alpha expression. In addition, EGCG exerted significant protection against microglial activation-induced neuronal injury both in the human dopaminergic cell line SH-SY5Y and in primary rat mesencephalic cultures. Our study demonstrates that EGCG is a potent inhibitor of microglial activation and thus is a useful candidate for a therapeutic approach to alleviating microglia-mediated dopaminergic neuronal injury in PD.

Analysis of Variance↗

PubMed2004

Accounting for leadtime in cohort studies: evaluating when to initiate HIV therapies.

Commonly reported comparisons of differences in disease progression according to disease staging at therapy initiation may be subject to bias if they do not account for the time it took the deferred group to reach the latter stage (that is, leadtime) and for previous events in those who initiate therapy at late stage (that is, unseen fast progressors). To estimate the impact of deferring initiation of highly active antiretroviral therapies (HAART) on time to clinical AIDS in the context of data from observational cohort studies, we describe a method that capitalizes on data from a pre-HAART period to multiply impute estimated leadtimes and the unseen events among fast progressors. After accounting for leadtime and the unseen events, data from two large cohort studies (N=739) indicate that deferring HAART initiation until CD4 is below 200 cells/mm3 was detrimental compared to initiating between 201 and 350 (hazard ratio=1.97; 95 percent confidence interval [CI] 1.09, 3.54), and that failure to account for leadtime resulted in a 38 per cent higher hazard ratio. In contrast, initiating HAART between 201 and 350 did not increase the hazard of AIDS compared to initiating with CD4 between 351 and 500 cells/mm3 (hazard ratio=0.70; 95 per cent CI 0.35, 1.42). Methods presented here offer an approach to analysing prevalent cohort studies and provide procedures to maximize the usefulness of observational data.

Adult↗

PubMed2004

Slowly developing depression of N-methyl-D-aspartate receptor mediated responses in young rat hippocampi.

BACKGROUND: Activation of N-methyl-D-aspartate (NMDA) type glutamate receptors is essential in triggering various forms of synaptic plasticity. A critical issue is to what extent such plasticity involves persistent changes of glutamate receptor subtypes and many prior studies have suggested a main role for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in mediating the effect. Our previous work in hippocampal slices revealed that, under pharmacological unblocking of NMDA receptors, both AMPA and NMDA receptor mediated responses undergo a slowly developing depression. In the present study we have further addressed this phenomenon, focusing on the contribution via NMDA receptors. Pharmacologically isolated NMDA receptor mediated excitatory postsynaptic potentials (EPSPs) were recorded for two independent synaptic pathways in CA1 area using perfusion with low Mg2+ (0.1 mM) to unblock NMDA receptors. RESULTS: Following unblocking of NMDA receptors, there was a gradual decline of NMDA receptor mediated EPSPs for 2-3 hours towards a stable level of ca. 60-70 % of the maximal size. If such an experimental session was repeated twice in the same pathway with a period of NMDA receptor blockade in between, the depression attained in the first session was still evident in the second one and no further decay occurred. The persistency of the depression was also validated by comparison between pathways. It was found that the responses of a control pathway, unstimulated in the first session of receptor unblocking, behaved as novel responses when tested in association with the depressed pathway under the second session. In similar experiments, but with AP5 present during the first session, there was no subsequent difference between NMDA EPSPs. CONCLUSIONS: Our findings show that merely evoking NMDA receptor mediated responses results in a depression which is input specific, induced via NMDA receptor activation, and is maintained for several hours through periods of receptor blockade. The similarity to key features of long-term depression and long-term potentiation suggests a possible relation to these phenomena. Additionally, a short term potentiation and decay (<5 min) were observed during sudden start of NMDA receptor activation supporting the idea that NMDA receptor mediated responses are highly plastic.

Animals↗

PubMed2004

Highly active antiretroviral therapy and cervical squamous intraepithelial lesions in human immunodeficiency virus-positive women.

BACKGROUND: Women infected with human immunodeficiency virus (HIV) have an increased risk of persistent squamous intraepithelial lesions (SILs) of the cervix. We assessed the association between use of highly active antiretroviral therapy (HAART) and regression of SIL in HIV-infected women enrolled in the Women's Interagency HIV Study, a large, multicenter, prospective cohort study. METHODS: Of 2059 HIV-infected participants, 312 HIV-infected women had normal cervical cytology at baseline and were subsequently diagnosed during 7 years of follow-up with incident SIL. Pap smears, CD4+ T-cell counts, and information regarding use of HAART were obtained every 6 months. The outcome of interest was lesion regression, defined as two consecutive normal Pap smears 6 months apart. Incidence rates of SIL regression were computed among person-years at risk, both before and after HAART initiation. All statistical tests were two-sided. RESULTS: Of 312 women, 141 had lesions that regressed to normal cytology, with a median time to regression of 2.7 years. Overall, the incidence of regression increased (P(trend) =.002) over time after HAART was introduced. At incident SIL, median CD4+ T-cell counts were lower in women whose lesions did not regress than in women whose lesions regressed (230 versus 336 cells/microL; P<.01). Before HAART was introduced, the rate of lesion regression was 0.0% (95% confidence interval [CI' = 0.0% to 2.4%). After HAART was introduced, the rate was 12.5% (95% CI = 9.9% to 15.1%) and was related to post-HAART CD4+ T-cell counts (P(trend) =.002). CONCLUSIONS: HAART use was associated with increased regression of SIL among HIV-infected women, and among women who used HAART, increased CD4+ T-cell counts were associated with a greater likelihood of regression. However, the majority of cervical lesions among HIV-infected women, even among individuals who used HAART, did not regress to normal.

AIDS-Related Opportunistic Infections↗

PubMed2004

Protein preparation, crystallization and preliminary X-ray analysis of human adrenal gland protein AD-004.

The adrenal gland protein AD-004 was identified in the human adrenal gland. Full-length AD-004 contains 172 amino acids, with a predicted molecular weight of about 20 kDa. In attempts to crystallize human AD-004, the gene was subcloned into a modified pET vector, pET21-DEST, with an N-terminal His(5) tag using the Gateway cloning system, followed by protein expression in Escherichia coli strain BL21(DE3). The protein was purified in two steps to near-homogeneity and was crystallized. The crystals belong to space group P6(1) or P6(5), with unit-cell parameters a = b = 99.56, c = 57.19 A. A complete 2.0 A data set has been collected at a rotating-anode X-ray source and structure determination is under way.

Adrenal Glands↗

PubMed2004

Characterization of NMDA induced depression in rat hippocampus: involvement of AMPA and NMDA receptors.

The involvement of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) vs. N-methyl-d-aspartate (NMDA) receptor mediated changes in NMDA-induced long-term depression (LTD) was assessed by monitoring isolated AMPA, isolated NMDA and composite field excitatory postsynaptic potentials (EPSP) in the CA1 area of acute rat hippocampal slices. Application of NMDA (20-50 microM) for 3-5 min led to LTD of both AMPA and NMDA receptor mediated EPSPs with near equal changes of the responses. However, AMPA EPSPs displayed a faster initial recovery than NMDA EPSPs. In addition, during the first 15-25 min after NMDA application, there was a superimposed potentiation of the later, but not early, part of AMPA EPSPs, implying a prolongation of waveform. In contrast, the NMDA EPSP waveform remained unaltered throughout the experiments. While it has been maintained that NMDA-induced depression is equivalent to stimulus-induced LTD, our results reveal additional complexity, suggesting a multitude of changes, most likely at the postsynaptic receptor level.

Animals↗

PubMed2004

Targeting and amplification of immune killing of tumor cells by pro-Smac.

Overexpression of inhibitors of apoptosis (IAP) is one potential mechanism for tumor cells to evade immune surveillance. To determine whether immune-mediated killing of tumor cells can be enhanced by neutralization of IAP proteins, 2 novel eGFP-Smac fusion proteins (pro-Smac) were introduced into the poorly immunogenic mouse melanoma cell line, B16BL6-D5 (D5). Each fusion protein contained Smac and a cleavage site specific for granzyme B (GrB) or caspase 8, thereby targeting the 2 major killing mechanisms of cytotoxic T-lymphocyte (CTL) and NK cells. Expression of a pro-Smac fusion protein by D5 tumor cells greatly enhanced the susceptibility to killing by lymphokine-activated killer (LAK) cells or purified GrB. GrB-mediated killing was increased to a much greater extent when tumor cells expressed the eGFP-Smac fusion protein with a GrB cleavage site compared to a caspase 8 cleavage site. In contrast, perforin-deficient LAK cells, which lack GrB-mediated cytotoxicity but process normal ligands for death receptors, killed D5 tumor cells expressed pro-Smac with caspase 8 cleavage site more efficiently. Enhanced killing by GrB was also accompanied by processing of the fusion protein and increased caspase-3-like activity. These results indicate that killing of tumor cells can be amplified by targeting cell-mediated cytotoxic mechanisms via expression of pro-Smac fusion proteins.

Animals↗

PubMed2004

Registration of medical images using an interpolated closest point transform: method and validation.

Image registration is an important procedure for medical diagnosis. Since the large inter-site retrospective validation study led by Fitzpatrick at Vanderbilt University, voxel-based methods and more specifically mutual information-based registration methods (see for instance [IEEE Trans. Med. Imag. 22 (8) (2003) 986] for a review on these methods) have been regarded as the method of choice for rigid-body intra-subject registration problems. In this study we propose a method that is based on the Iterative Closest Point algorithm and a pre-computed closest point map obtained with a slight modification of the fast marching method proposed by Sethian. Pre-computing the closest point map speeds up the process because at each iteration point correspondence can be established by table lookup. We also show that because the closest point map is defined on a regular grid it introduces a registration error and we propose an interpolation scheme that addresses this issue. The method has been tested both on synthetic and real images, and registration results have been assessed quantitatively using the data set provided by the Retrospective Registration Evaluation Project. For these volumes, MR and CT head surfaces were extracted automatically using a level-set technique. Results show that on these data sets this registration method leads to accuracy numbers that are comparable to those obtained with voxel-based methods.

Algorithms↗

PubMed2004

Characterizing changes in MR images with color-coded Jacobians.

Image registration is the process of establishing spatial correspondence between two images or between two image volumes. Registration can be achieved by rigid, elastic, or a combination of rigid and elastic transforms that attempt to bring the two images into coincidence. A rigid transform accounts for differences in positioning and an elastic transform describes deformations due to differences in tissue properties, temporal changes due to growth or atrophy, or differences between individuals. Deformation-based morphometry uses the resulting deformation fields from these transforms to evaluate differences between the images being registered. Three methods of registration were evaluated: rigid (affine) transformation, elastic optical flow transformation, and elastic spline transformation. All three methods produce vector deformation fields that map each point in one image to a point in the other image. A 12-color map of the transformation Jacobian was used to represent local volume changes. Using the three registration methods, color-mapped Jacobians were determined using a simulated three-dimensional block with known translation, rotation, expansion, contraction, and intensity modulations. Color-coded Jacobians were also generated for experimentally measured magnetic resonance image volumes of water-filled balloons and 7-year-old twin boys. Color-coded Jacobians overlaid on anatomical images provide a convenient method to identify regional tissue expansion and contraction.

Algorithms↗

PubMed2004

Regression of bone metastases following adoptive transfer of anti-CD3-activated and IL-2-expanded tumor vaccine draining lymph node cells.

As many as 80% of patients with breast, prostate, or lung cancer develop bone metastases during the course of their illness. However, thus far, no attempts have been made to explore the potential value of adoptive immunotherapy with antigen-specific T lymphocytes specifically for the treatment of skeletal metastases. Here, we demonstrate tumor regression in a preclinical model of bone metastases from the murine B16BL6 melanoma following adoptive transfer of effector T lymphocytes obtained from tumor vaccine draining lymph nodes. The antitumor effect required transfer of high number of effector cells, which was dependent on CD8+ cells as demonstrated by in vivo depletion of different T cell subsets, and was magnified if effector cells were administered to the arterial supply of the bone/bone marrow. Using flow cytometric analysis, CFSE-labelled Thy1.1+ donor T cells were isolated from the bone marrow of tumor-bearing mice at 24 h and 6 days following adoptive transfer. At the latter time point cell division of the transferred effector cells was detectable. Currently, no curative treatment is known for skeletal metastases in clinical practice. Considering the promising early findings in the present study, further studies exploring the therapeutic potential of adoptive immunotherapy for metastatic disease to the skeleton are warranted.

Animals↗

PubMed2004

Novel endothelial cell markers in hepatocellular carcinoma.

Hepatocellular carcinoma is characterized by hypervascularity and a propensity for vascular invasion. Detailed analysis of complementary DNA (cDNA) microarray global gene expression data and further validation on a smaller independent sample set by reverse transcription-polymerase chain reaction established the presence of two endothelial gene clusters in hepatocellular carcinoma. Cluster I, consists of 20 cDNA clones, representing 15 unique genes. Cluster II consists of nine unique genes. The expression of the cluster I genes appeared to be significantly upregulated in hepatocellular carcinoma compared with normal liver, cirrhotic liver, or nontumor liver tissues adjacent to the hepatocellular carcinoma. The pattern of gene expression of cluster I genes correlated positively with the 'proliferation gene cluster' and 'stromal cells cluster 2'. Expression of cluster II genes, in contrast, was not significantly different between hepatocellular carcinoma and non-neoplastic liver tissues. Studies conducted to localize the protein products of these genes by immunohistochemical staining of tissue arrays with up to 350 cores of tissues, and by in situ hybridization led to the discovery of novel sinusoidal endothelial cell markers in hepatocellular carcinoma: podocalyxin-like and regulator of G protein signaling-5. Our results underscore fundamental differences not only between neoplastic vs non-neoplastic liver cells but also between the hepatic sinusoidal endothelium of hepatocellular carcinoma and normal liver.

Antigens, CD34↗

PubMed2004

Expression profiling identifies chemokine (C-C motif) ligand 18 as an independent prognostic indicator in gastric cancer.

BACKGROUND & AIMS: Gastric cancer is one of the major cancers worldwide. Expression profiling has proven useful in delineating novel prognostic markers in various cancer types. We previously analyzed gene-expression patterns in 90 gastric adenocarcinomas by using complementary DNA microarrays and prioritized a list of genes whose expression levels predict patient outcome. METHODS: We identified a specific gene of interest, chemokine (C-C motif) ligand 18 (CCL18), on the basis of a high absolute standardized log Cox hazard ratio, a high variance in expression among all tumor samples, and putative biologic function. Detailed analysis of CCL18 expression with clinicopathologic and survival data was performed (n = 89). Quantitative reverse-transcription polymerase chain reaction was used to verify the microarray expression data and was further applied to analyze an independent cohort of tumor samples (n = 59). The cellular source of CCL18 was determined with immunohistochemistry and in situ hybridization. RESULTS: High CCL18 expression levels were associated with prolonged overall (P = 0.001; hazard ratio, 0.586) and disease-free (P = 0.002; hazard ratio, 0.416) patient survival in the array-based data set by univariate analysis. The observations were confirmed in an independent set of 59 patients by using quantitative reverse-transcription polymerase chain reaction. In multivariate analysis, tumor stage and CCL18 levels were independent prognostic factors for predicting both overall and disease-free survival. We found that CCL18 was expressed by a subpopulation of tumor-associated macrophages that were preferentially located at the tumor invasion front. CONCLUSIONS: Macrophage-derived CCL18 may function as a local antitumor immunomodulator that affects patient outcome. Our study suggests CCL18 as a novel candidate for antitumor therapeutics and risk stratification in gastric cancer patients.

Adenocarcinoma↗

PubMed2004

Perivascular innervation of penetrating brain parenchymal arterioles.

We investigated the functional heterogeneity of cerebral pial arteries that are extrinsically innervated versus penetrating brain parenchymal arterioles (PA) that are intrinsically innervated by comparing myogenic activity and reactivity to neurotransmitter. Pial middle cerebral arteries (MCA, n = 6) and PA (n = 6) that branched off the MCA and penetrated the brain tissue were isolated from male Wistar rats and studied in vitro under pressurized conditions for reactivity to serotonin (5-hydroxytryptamine, 5-HT), noradrenaline (NA), and indolactam-V (IL-V), a protein kinase C (PKC) agonist. In a separate group of vessels from the same locations (n = 12), perivascular nerve density was determined after staining for protein gene product 9.5 (PGP 9.5). PAs were significantly smaller than MCAs, and possessed greater myogenic tone at all pressures studied. MCAs reacted to both 5-HT and NA with concentration-dependent contraction, however, PA had little to no response to either neurotransmitter. The percent constriction to 5-HT and NA for MCA versus PA at the maximum concentration was: 31 +/- 6% versus 1.0 +/- 1.0% and 13 +/- 5% versus 2.6 +/- 1.8% (P < 0.01). However, both types of vessels contracted with similar reactivity to PKC activation with IL-V (41 +/- 4% versus 37 +/- 7%, ns). Perivascular nerve density correlated with reactivity such that MCAs were densely innervated with varicose fibers within the adventitia; however, PA had very few or no adventitial fibers. The differential response to neurotransmitter suggests that there is significant heterogeneity in the cerebral circulation. It appears that in PA, the dominant vasoconstricting stimulus is intrinsic myogenic tone and that the role of neurotransmitter and intrinsic innervation is beyond that of controlling CBF.

Animals↗