The Application of Pneumatic Arm in Neuroendoscopic Transsphenoidal Pituitary Adenoma Resection.

OBJECTIVE: To summarize the application experience of the pneumatic arm in transnasal sphenoidal pituitary adenoma resection under neuroendoscope. METHODS: A retrospective analysis was conducted on the clinical data of 52 patients with pituitary adenoma who underwent endoscopic transsphenoidal surgery with pneumatic arm fixation in the Neurosurgery Department of the First Affiliated Hospital of Anhui Medical University from July 2021 to March 2024. Among them, there were 5 cases of pituitary microadenoma, 35 cases of macroadenoma, and 12 cases of giant adenoma. Head CT and a full set of hormones were re-examined within 24 hours after surgery to evaluate the surgical effect. Follow-up was conducted by the outpatient department after surgery to assess the clinical symptoms, hormone level, and imaging of all patients. RESULTS: Among 52 patients, gross total resection was achieved in 48 cases (92.3%), subtotal resection in 3 cases (5.8%), and partial resection in 1 case (1.9%). Preoperatively, 43 patients had diminished vision, with 40 showing improvement postoperatively, 1 worsening, and 2 having no significant improvement. Thirty-eight patients had headaches preoperatively, and all showed varying degrees of improvement postoperatively. Routine hormone examination within 24 hours after surgery showed that all 20 prolactinoma patients had restored normal hormone levels, 10 of 12 growth hormone-secreting adenoma patients normalized, and 4 of 6 cases of adrenocorticotropic hormone-secreting adenoma immediately relieved after surgery. Postoperative complications included intracranial hematoma in 1 case, cerebrospinal fluid leakage in 2 cases, transient diabetes insipidus in 6 cases, intracranial infection in 1 case, and no death cases. The median follow-up time of 52 patients was 18.6 months (range: 1-32 mo). During the follow-up period, the initial clinical symptoms of all patients improved to varying degrees, and they were able to work and live normally. At the last follow-up, 1 patient had recurrent tumor and 1 patient had progression. CONCLUSION: Transnasal sphenoidal resection of pituitary adenoma using a pneumatic arm-fixed neuroendoscope allows the operator to perform the surgery with both hands, resulting in satisfactory overall tumor resection and fewer surgical complications. This technique has good clinical value for promotion.

Evidence for an intra-tumoral microbiome in pituitary neuroendocrine tumors with different clinical phenotypes.

PURPOSE: Bacteria have been observed in the tumor environment for decades and have been demonstrated to play important roles in the pathogenesis and development of several different tumors. So far there is a clear lack of specific studies relating to the presence of bacteria in pituitary neuroendocrine tumors (PitNETs). METHODS: In this study, we performed five region-based amplification and bacterial 16 S rRNA sequencing to identify the microbiome of PitNET tissues across four clinical phenotypes. Multiple filter procedures were performed to inhibit the risk of contamination with bacteria and bacterial DNA. Histological analysis was also conducted to validate the localization of bacteria in the intra-tumoral region. RESULTS: We identified common and diverse bacterial types across the four clinical phenotypes of PitNET. We also predicted the potential functions of these bacteria in tumor phenotypes and found that these functions were reported in certain previous mechanistic studies. Our data indicate that the pathogenesis and development of tumors may correlate with the behavior of intra-tumoral bacteria. Histological results, including lipopolysaccharide (LPS) staining and fluorescence in situ hybridization (FISH) for bacterial 16 S rRNA clearly demonstrated the localization of bacteria in the intra-tumoral region. Staining for Iba-1 suggested that the proportion of microglia was more abundant in FISH-positive regions than in FISH-negative regions. Furthermore, in FISH-positive regions, the microglia exhibited a longitudinally branched morphology that was different to the compact morphology observed in FISH-negative regions. CONCLUSION: In summary, we provide an evidence for the existence of intra-tumoral bacteria in PitNET.

"Rapid Formation, Acute Rupture" Course of Intracranial Aneurysm.

Intracranial aneurysm (IA) is a devastating cerebrovascular disease characterizing with a potential rupturing risk. In previous studies, the formation of IA was considered to be in a chronic manner, and the ruptured aneurysms might merely derived from the already formed unruptured IA. A 61-year-old male presented to the hospital complaining of a headache. The patient received neuroimage tests, including head computed tomography and digital substraction angiography, to examine the underlying cerebrovascular diseases. Interestingly, we found a newborn ruptured IA with 9-day intervals between 2 whole-cerebral digital subtraction angiography examinations. In summary, the case in our report provides a clue for the natural course that the IA is probably in a "rapid formation, acute rupture" manner.

Intracranial Infiltration of a Scalp Neoplasm After Hair Dyeing 10 Years Ago.

ABSTRACT: Cosmetics with unknown chemical components may cause unexpected cancers. Here, we report a rare case of hair dye-induced intracranial communicating scalp sebaceous carcinoma in a young female who dyed her hair 10 years ago. The histological origin of the intracranial communicating neoplasm was of priority for subsequent therapeutic decisions, therefore, requiring comprehensive diagnostic strategy. In conclusion, this case report emphasizes careful evaluation of the long-term risks for unlabeled cosmetics.

CSF1 expression in nongynecological leiomyosarcoma is associated with increased tumor angiogenesis.

Leiomyosarcoma (LMS) is a malignant tumor of smooth muscle cells for which few effective therapies exist. A subset of LMS cases express macrophage colony-stimulating factor (CSF1) and the resultant tumor-associated macrophage (TAM) infiltration predicts poor clinical outcome. Further, TAMs have been shown to increase tumor angiogenesis. Here, we analyzed 149 LMS cases by immunohistochemistry for vascular marker CD34 and show that high microvessel density (MVD) in nongynecological LMS cases significantly predicts poor patient outcome. The majority of high MVD cases were also CSF1-positive, and when combining high MVD with CSF1 expression, an even stronger prognostic correlation with patient outcome was obtained. Gene expression profiling revealed that MVD has a stronger correlation with CSF1 expression than with expression of vascular endothelial growth factor isoforms, which have traditionally been used as markers of angiogenesis and as anti-angiogenic therapeutic targets. Finally, patterns of CSF1 expression and TAM recruitment remained consistent between primary tumors and their metastases, and between primary tumors and those grown as xenografts in mice, highlighting the stability of these features to the biology of LMS tumors. Together, these findings suggest an important role for CSF1 and the resulting TAM infiltration in the pathological neovascularization of LMS tumors and provide a rationale for CSF1-targeted therapies in LMS.

Nanosensitizers for sonodynamic therapy for glioblastoma multiforme: current progress and future perspectives.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood-brain barrier (BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy (SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.

High Expression of CISD2 in Relation to Adverse Outcome and Abnormal Immune Cell Infiltration in Glioma.

Glioma is a serious disease burden globally, with high mortality and recurrence rates. CDGSH iron sulfur domain 2 (CISD2) is an evolutionarily conserved protein that is involved in several cancers. However, its role in the prognosis and immune infiltration in glioma remains unclear. In our research, RNA-seq matrix and clinicopathological relevant data for CISD2 were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Human Protein Atlas was used to verify the CISD2 protein level in glioma, and STRING was used to establish relative coexpression gene network. The Kaplan-Meier plotter was adopted to analyze the effect of CISD2 on prognosis. The connection between CISD2 expression and immune infiltration was analyzed using single-sample GSEA (ssGSEA), TIMER, and GEPIA. In contrast to normal tissues, CISD2 expression was significantly higher in glioma tissues, and CISD2 presented a certain diagnostic value in distinguishing glioma tissues from normal tissues. Furthermore, the CISD2 level was correlated with age, histologic grade, histological type, isocitrate dehydrogenase (IDH) status, 1p/19q codeletion status, and primary therapy outcome of glioma, while high CISD2 mRNA expression was correlated with grave overall survival. Multivariate analysis demonstrated that CISD2 was an independent risk factor for patients with glioma. Functional enrichment analysis indicated that CISD2 could regulate proliferation, immune reaction, and mitochondrial function. The results from the ssGSEA and TIMER databases confirmed that CISD2 acts a prominent role in immune cell infiltration in the tumor microenvironment, especially in low-grade glioma (LGG). Furthermore, CISD2 expression was observably correlated to M2 polarization in macrophages with glioma progression. This is the first research to investigate the immune role of CISD2 in glioma. CISD2 may be an innovative prognostic biomarker and can act as a potential target for future therapy for glioma.

Engineering nanotheranostic strategies for liver cancer.

The incidence and mortality of hepatocellular carcinoma have continued to increase over the last few years, and the medicine-based outlook of patients is poor. Given great ideas from the development of nanotechnology in medicine, especially the advantages in the treatments of liver cancer. Some engineering nanoparticles with active targeting, ligand modification, and passive targeting capacity achieve efficient drug delivery to tumor cells. In addition, the behavior of drug release is also applied to the drug loading nanosystem based on the tumor microenvironment. Considering clinical use of local treatment of liver cancer, in situ drug delivery of nanogels is also fully studied in orthotopic chemotherapy, radiotherapy, and ablation therapy. Furthermore, novel therapies including gene therapy, phototherapy, and immunotherapy are also applied as combined therapy for liver cancer. Engineering nonviral polymers to function as gene delivery vectors with increased efficiency and specificity, and strategies of co-delivery of therapeutic genes and drugs show great therapeutic effect against liver tumors, including drug-resistant tumors. Phototherapy is also applied in surgical procedures, chemotherapy, and immunotherapy. Combination strategies significantly enhance therapeutic effects and decrease side effects. Overall, the application of nanotechnology could bring a revolutionary change to the current treatment of liver cancer.

A simple lectin-based biochip might display the potential clinical value of glycomics in patients with spontaneous intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a cerebrovascular disease with extremely high disability and mortality rates. Glycans play critical roles in biological processes. However, whether glycans can serve as potential biomarkers for determining clinical diagnosis and prognosis in ICH remains determined. METHODS: In this study, we established a lectin-biochip to measure serum glycans levels in ICH patients (n=48) and healthy controls (n=16). An enzyme-linked immunosorbent assay (ELISA) was carried out to determine serum levels of IL-10 and TNF-α in the patients. Correlation analyses of the serum glycan and cytokine levels and the clinicopathological parameters of patients were performed. RESULTS: The biochip-based data revealed that the serum levels of α-Man/α-Glc (ConA), Galß3GalNAc (PNA), GalNAc (VVA), Fucα6GlcNAc (AAL), α-Fuc (LTL), and Galß3GalNAc-Ser/Thr (AIL) significantly increased in the super-acute phase of ICH in comparison with healthy controls. Clinicopathological analysis indicated the serum levels of ConA, VVA, and LTL had significant associations with the National Institute of Health Stroke Scale (NIHSS), and serum VVA levels had a significant association with the Mini-Mental State Examination (MMSE) at day 90 after ICH. Correlation coefficient analysis revealed significant correlations between TNF-α and ConA (P<0.001) as well as between IL-10 and ConA (P<0.001), PNA (P=0.02), VVA (P<0.001), and MAL (P=0.04), respectively. CONCLUSIONS: We established a proof-of-concept platform for detecting serum glycomics and highlighted their potential value in diagnosing and predicting ICH patients' outcomes.

Neurotoxic role of interleukin-17 in neural stem cell differentiation after intracerebral hemorrhage.

Interleukin 17 (IL-17) and its main producer, T cell receptor γδ cells, have neurotoxic effects in the pathogenesis of intracerebral hemorrhage (ICH), aggravating brain injuries. To investigate the correlation between IL-17 and ICH, we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients. There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients (r = -0.498, P < 0.01). To study the neurotoxic role of IL-17, C57BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus. Subsequently, the mice were treated with mouse neural stem cells (NSCs) and/or IL-17 neutralizing antibody for 72 hours. Flow cytometry, brain water content detection, Nissl staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue, but there was no difference in T cell receptor γδ cells. Compared with the ICH group, there were fewer apoptotic bodies and more Nissl bodies in the ICH + NSC group and the ICH + NSC + IL-17 group. To investigate the potential effect of IL-17 on directional differentiation of NSCs, we cultured mouse NSCs (NE-4C) alone or co-cultured them with T cell receptor γδ cells, which were isolated from mouse peripheral blood mononuclear cells, for 7 days. The results of western blot assays revealed that IL-17 secreted by T cell receptor γδ cells reduced the differentiation of NSCs into astrocytes and neurons, while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons. In conclusion, serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients. Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of NSCs. The application of IL-17 neutralizing antibody may promote the directional differentiation of NSCs into astrocytes. This study was approved by the Clinical Research Ethics Committee of Anhui Medical University of China (For human study: Approval No. 20170135) in December 2016. All animal handling and experimentation were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University (approval No. 20180248) in December 2017.

Cerebral hemodynamics and brain functional activity during lower body negative pressure.

INTRODUCTION: Exposure to high +Gz acceleration forces on a centrifuge or in an aircraft can severely decrease cerebral blood perfusion and cause rapid G-induced loss of consciousness. However, milder acceleration may gradually reduce cerebral blood flow and affect cognitive function in subtler ways. This study used lower body negative pressure (LBNP) to mimic +Gz circulatory effects in order to study cerebral hemodynamics and brain function. METHODS: Subjects were 15 healthy men, 19-21 yr of age. They were exposed to LBNP at two levels for 5 min each separated by a 10-min recovery period. The conditions were low (LO), -4.00 kPa (-30 mmHg) and high (HI), -6.67 kPa (-50 mmHg).Variables measured before, during, and after LBNP included cerebral blood flow velocity (CBFV) in the middle cerebral artery, blood oxygen saturation (SaO2), heart rate (HR), blood pressure, P300 of event-related EEG potentials, reaction time, and tracking error. RESULTS: LO significantly reduced CBFV at 4 and 5 min, increased HR, and decreased the amplitude of P300, but none of the other variables changed from baseline. In contrast, HI produced significant changes in most variables: CBFV decreased at 2 min and then fell further at 4 and 5 min, HR increased, and SaO2 decreased. Significant neurocognitive changes included increased latency and reduced amplitude of P300, slower reaction time, and greater tracking error. CONCLUSION: The higher level of LBNP used here reduced cerebral perfusion sufficiently to impair neurocognitive function. This model may be useful for further studies of these and other variables under closely controlled conditions.

[Changes in voltage-dependent calcium channel currents of vascular smooth muscle cells isolated from small mesenteric arteries of simulated weightless rats].

The aim of the present study was to examine the changes in the function of voltage-dependent calcium channels (VDC) of vascular smooth muscle cells (VSMCs) isolated from small mesenteric arteries of rats subjected to 1-week or 4-week simulated weightlessness. The whole-cell recording mode was used to record current densities and Ba(2+) was used as charge carrier. Curves and fitting parameters describing steady-state activation and inactivation characteristics of VDC were thus obtained. The inward currents recorded from the VSMCs of small mesenteric arteries were mainly the Ba(2+) currents through the long-lasting type VDC (L-VDC). Compared with that of the control rats, the L-VDC current density of VSMCs from small mesenteric arteries showed a trend toward a decrease in the rats after 1-week , while a significant decrease was observed in the rats after 4-week simulated weightlessness. However, there were no significant differences in the opening and closing rates of L-VDCs, the position of steady-state activation and inactivation curves, and in the parameters, V(0.5) and k, between either of the two groups and its respective control group. The membrane capacitance and the reversal potential of the VSMCs from the small mesenteric arteries of rats after simulated weightlessness also showed no significant changes. These findings suggest that the decreased function of the L-VDC in hindquarter VSMCs might be one of the electrophysiological mechanisms that mediate the depressed vasoreactivity and atrophic change in hindquarter arteries during adaptation to simulated weightlessness in rats.

[Enhanced BK(Ca) single-channel activities in cerebrovascular smooth muscle cells of simulated microgravity rats.].

The aim of the present study was to investigate the changes in single-channel currents of large conductance calcium-activated potassium channels (BK(Ca) channels) in cerebral vascular smooth muscle cells (VSMCs) of rats after 1-week simulated microgravity. Sprague-Dawley rats were subjected to tail-suspension (SUS) to simulate cardiovascular deconditioning due to microgravity. Cytosolic calcium ([Ca(2+)](i)) was examined by laser-scanning confocal microscopy with calcium-sensitive-dye Fluo-3/AM as fluorescent probe. Single-channel currents of BK(Ca) channels were measured with cell-attached membrane patches bathed in symmetrical high potassium solution. The [Ca(2+)](i)i level was significantly higher in cerebrovascular myocytes of SUS than that of control (CON) rats. The probability of open (Po) and the mean open time (To) of BK(Ca) channels in cerebral VSMCs significantly increased in SUS as compared with CON. However, there were no significant differences in the unitary conductance and mean close time (Tc) between the two groups. The results obtained suggest that both the elevated [Ca(2+)](i) and enhanced single-channel activities of BK(Ca) channels in cerebral VSMCs might be among the electrophysiological mechanisms that mediate the increased vasoreactivity and hypertrophic change in cerebral arteries during adaptation to simulated microgravity in rats.

[Changes in potassium currents of vascular smooth muscle cells isolated from hindquarter arteries of rats after 4 weeks simulated weightlessness].

The changes in potassium currents of vascular smooth muscle cells (VSMCs) isolated from saphenous arteries and the 2nd-6th order branches of the mesenteric arteries of 4-week tail-suspended rats (SUS) were examined using whole cell patch clamp technique. The resting potential (RP) of the VSMCs from SUS group was more negative compared with that of the control group (CON).The whole cell potassium current densities of VSMCs isolated from the saphenous arteries and small mesenteric arteries in SUS group were significantly larger than those of the CON group.The BK(Ca) and K(V) current densities of VSMCs from saphenous arteries and small mesenteric arteries from SUS group were also significantly larger than those from the CON group.It is speculated that the hyperpolarization of VSMCs and decreased calcium influx through voltage-dependent calcium channels might be one of the electrophysiological mechanisms involved in the depressed vasoreactivity of hindquarter arteries induced by simulated weightlessness.

[Changes of human cerebral blood flow velocity and blood oxygen saturation under lower body negative pressure in upright seated position].

Objective. To investigate the effect of lower body negative pressure (LBNP) in upright seated position on cerebral blood flow velocity, heart rate (HR), and blood oxygen saturation (SaO2) in human. Method. Fifteen young men were selected as subjects. Blood flow velocity in middle cerebral artery (VMCA), HR and SaO2 were measured at 0.5, 1, 2, 3, 4, and 5 min during LBNP and 1, 3, 5 min after -4.00 kPa and -6.67 kPa LBNP in upright seated position respectively. Result. Under -4.00 kPa LBNP, VMCA slowed down at 4, 5 min during LBNP (P<0.05), and HR speeded up at 3, 4, 5 min during LBNP (P<0.05). There were no significant changes of SaO2. Under -6.67 kPa LBNP, VMCA became slow at 2, 3 min (P<0.05), and at 4 and 5 min (P<0.01) during LBNP. At 1 min after release of LBNP, VMCA did not recover, after which it recovered to control level. HR significantly increased (P<0.01) and SaO2 decreased at 5 min (P<0.05) during LBNP. Conclusion. LBNP can cause blood pooling in lower body so that VMCA and brain blood volume decrease. Then it causes loss of consciousness. The results of this experiment may provide experimental data for diagnosis of flight syncope and orthostatic intolerance.

[Changes of potassium channel activity of hindlimb arterial smooth muscle cells in tail-suspended rats].

OBJECTIVE: To examine the change of potassium channel function in hindlimb arterial smooth muscle cells in tail-suspended rats and to elucidate the underlying electro-physiological mechanisms responsible for the depressed vascular responsiveness of hindlimb arteries induced by simulated weightlessness. METHOD: The contractile responsiveness of femoral arterial rings of 1-wk and 4-wk tail-suspended rats to potassium channel blockers, tetraethylammonium chloride (TEA) and 4-aminopyridine (4-AP), were recorded, and the currents of large conductance calcium-dependent potassium channel (BK(Ca)) and voltage activated potassium channel (Kv) of vascular smooth muscle cells (VSMCs) in saphenous arteries from 1-wk tail-suspended rats were recorded using the whole cell recording mode of patch clamp technique. RESULT: The femoral arteries from of 1-wk and 4-wk tail-suspended rats showed a decreased contractile response to 60 mM KCl, and the ratio of their contractile responses induced by TEA or 4-AP to their responses induced by 60 mM KCl increased significantly after 1-wk and 4-wk simulated weightlessness. However no difference was found between 1-wk and 4-wk tail-suspended rats. The whole cell current recording showed that BK(Ca) current densities and K(v) current densities of VSMCs in saphenous artery increased significantly after 1-wk simulated weightlessness. CONCLUSION: The contractile response of hindlimb arteries to KCl decreased after simulated weightlessness. The activities of BK(Ca) and K(v) of smooth muscle cells in hindlimb arteries from tail-suspended rats increased, and these changes might be among the electro-physiological mechanisms involved in the depressed vasoreactivity of hindlimb arteries due to simulated weightlessness.

Synuclein-γ suppression mediated by RNA interference inhibits the clonogenicity and invasiveness of MCF-7 cells.

The aim of the present study was to investigate the effects of synuclein-γ (SNCG) downregulation by RNA interference (RNAi) on the clonogenicity and invasiveness of MCF-7 breast cancer cells. This study used four pairs of SNCG-specific siRNAs which were designed and cloned into the pGPU6 plasmid for introduction into an MCF-7 cell line. The SNCG knockdown efficacies of the four siRNAs were compared using the reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. The cells' clonogenic and invasive phenotypes were examined with clonogenic and Boyden chamber assays. In comparison with the non-specific siRNA and empty vector controls, all four SNCG siRNAs were observed to significantly inhibit SNCG expression at the mRNA and protein levels (F=481.06, P<0.001; F=147.42, P<0.0001). SNCG suppression mediated by RNAi successfully inhibited the clonogenicity (P=0.002) and invasiveness (P<0.001) of transfected MCF-7 cells. According to the results of the present study, we concluded that SNCG suppression mediated by RNAi significantly suppressed SNCG expression at the mRNA and protein levels, suggesting that SNCG suppression mediated by an RNAi strategy may become a novel approach for treating advanced breast cancer.

Functional alterations in cerebrovascular K(+) and Ca(2+) channels are comparable between simulated microgravity rat and SHR.

Exposure to microgravity leads to a sustained elevation in transmural pressure across the cerebral vasculature due to removal of hydrostatic pressure gradients. We hypothesized that ion channel remodeling in cerebral vascular smooth muscle cells (VSMCs) similar to that associated with hypertension may occur and play a role in upward autoregulation of cerebral vessels during microgravity. Sprague-Dawley rats were subjected to 4-wk tail suspension (Sus) to simulate the cardiovascular effect of microgravity. Large-conductance Ca(2+)-activated K(+) (BK(Ca)), voltage-gated K(+) (K(V)), and L-type voltage-dependent Ca(2+) (Ca(L)) currents of Sus and control (Con) rat cerebral VSMCs were investigated with a whole cell voltage-clamp technique. Under the same experimental conditions, K(V), BK(Ca), and Ca(L) currents of cerebral VSMCs from adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were also investigated. K(V) current density decreased in Sus rats vs. Con rats [1.07 +/- 0.14 (n = 22) vs. 1.31 +/- 0.28 (n = 16) pA/pF at +20 mV (P < 0.05)] and BK(Ca) and Ca(L) current densities increased [BK(Ca): 1.70 +/- 0.37 (n = 23) vs. 0.88 +/- 0.22 (n = 19) pA/pF at +20 mV (P < 0.05); Ca(L): -2.17 +/- 0.21 (n = 35) vs. -1.31 +/- 0.10 (n = 26) pA/pF at +10 mV (P < 0.05)]. Similar changes were also observed in SHR vs. WKY cerebral VSMCs: K(V) current density decreased [1.03 +/- 0.33 (n = 9) vs. 1.62 +/- 0.64 (n = 9) pA/pF at +20 mV (P < 0.05)] and BK(Ca) and Ca(L) current densities increased [BK(Ca): 2.54 +/- 0.47 (n = 11) vs. 1.12 +/- 0.33 (n = 12) pA/pF at +20 mV (P < 0.05); Ca(L): -3.99 +/- 0.53 (n = 12) vs. -2.28 +/- 0.20 (n = 10) pA/pF at +20 mV (P < 0.05)]. These findings support our hypothesis, and their impact on space cardiovascular research is discussed.

Differential activation of potassium channels in cerebral and hindquarter arteries of rats during simulated microgravity.

The purpose of this study was to test the hypothesis that differential autoregulation of cerebral and hindquarter arteries during simulated microgravity is mediated or modulated by differential activation of K(+) channels in vascular smooth muscle cells (VSMCs) of arteries in different anatomic regions. Sprague-Dawley rats were subjected to 1- and 4-wk tail suspension to simulate the cardiovascular deconditioning effect due to short- and medium-term microgravity. K(+) channel function of VSMCs was studied by pharmacological methods and patch-clamp techniques. Large-conductance Ca(2+)-activated K(+) (BK(Ca)) and voltage-gated K(+) (K(v)) currents were determined by subtracting the current recorded after applications of 1 mM tetraethylammonium (TEA) and 1 mM TEA + 3 mM 4-aminopyridine (4-AP), respectively, from that of before. For cerebral vessels, the normalized contractility of basilar arterial rings to TEA, a BK(Ca) blocker, and 4-AP, a K(v) blocker, was significantly decreased after 1- and 4-wk simulated microgravity, respectively. VSMCs isolated from the middle cerebral artery branches of suspended rats had a more depolarized membrane potential (E(m)) and a smaller K(+) current density compared with those of control rats. Furthermore, the reduced total current density was due to smaller BK(Ca) and smaller K(v) current density in cerebral VSMCs after 1- and 4-wk tail suspension, respectively. For hindquarter vessels, VSMCs isolated from second- to sixth-order small mesenteric arteries of both 1- and 4-wk suspended rats had a more negative E(m) and larger K(+) current densities for total, BK(Ca), and K(v) currents. These results indicate that differential activation of K(+) channels occur in cerebral and hindquarter VSMCs during short- and medium-term simulated microgravity. It is further suggested that different profiles of channel remodeling might occur in VSMCs as one of the important underlying cellular mechanisms to mediate and modulate differential vascular adaptation during microgravity.