| 1. |
- Ahnstedt, Hilda, et al.
(author)
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Human cerebrovascular contractile receptors are upregulated via a B-Raf/MEK/ERK-sensitive signaling pathway.
- 2011
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In: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 12
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Journal article (peer-reviewed)abstract
- ABSTRACT: BACKGROUND: Cerebral ischemia results in a rapid increase in contractile cerebrovascular receptors, such as the 5-hydroxytryptamine type 1B (5-HT1B), angiotensin II type 1 (AT1), and endothelin type B (ETB) receptors, in the vessel walls within the ischemic region, which further impairs local blood flow and aggravates tissue damage. This receptor upregulation occurs via activation of the mitogen-activated protein kinase pathway. We therefore hypothesized an important role for B-Raf, the first signaling molecule in the pathway. To test our hypothesis, human cerebral arteries were incubated at 37°C for 48 h in the absence or presence of a B-Raf inhibitor: SB-386023 or SB-590885. Contractile properties were evaluated in a myograph and protein expression of the individual receptors and activated phosphorylated B-Raf (p-B-Raf) was evaluated immunohistochemically. RESULTS: 5-HT1B, AT1, and ETB receptor-mediated contractions were significantly reduced by application of SB-590885, and to a smaller extent by SB-386023. A marked reduction in AT1 receptor immunoreactivity was observed after treatment with SB-590885. Treatment with SB-590885 and SB-386023 diminished the culture-induced increase of p-B-Raf immunoreactivity. CONCLUSIONS: B-Raf signaling has a key function in the altered expression of vascular contractile receptors observed after organ culture. Therefore, specific targeting of B-Raf might be a novel approach to reduce tissue damage after cerebral ischemia by preventing the previously observed upregulation of contractile receptors in smooth muscle cells.
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| 2. |
- Ahnstedt, Hilda, et al.
(author)
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Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries.
- 2013
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4
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Journal article (peer-reviewed)abstract
- Male-female differences may significantly impact stroke prevention and treatment in men and women, however underlying mechanisms for sexual dimorphism in stroke are not understood. We previously found in males that cerebral ischemia upregulates contractile receptors in cerebral arteries, which is associated with lower blood flow. The present study investigates if cerebral arteries from men and women differ in cerebrovascular receptor upregulation.
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| 3. |
- Anderberg, Leif, et al.
(author)
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Distribution patterns of transforaminal injections in the cervical spine evaluated by multi-slice computed tomography.
- 2006
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In: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 15:10, s. 1465-1471
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Journal article (peer-reviewed)abstract
- Transforaminal injections are sometimes used for the diagnosis and treatment of painful conditions in the lumbar and to a lesser degree in the cervical spine. The technique is most often used when investigating/treating radiculopathy caused by degenerative disease. But how selective are the nerve root blocks? What possible structures other than the intended nerve root are affected from such injections? This study was undertaken in order to try to answer these questions, as no study focusing on the possible spread from the transforaminal selective nerve root blocks in the cervical spine has been performed earlier. In three groups of patients, each group including three patients, we injected three different volumes (0.6, 1.1 and 1.7 ml) with a transforaminal technique in the cervical spine. In all the injections, a small amount of contrast media was added. The spread of the injections were then investigated using multi-slice computed tomography with reconstructions. The imaging revealed a possible effect on other nerve roots than the intended ones when a larger volume was used for the root blocks. The spread was related to the injected volume as well as to local anatomy (size of foraminal area). In this study, only 0.6-ml injections could be accepted for being selective enough for diagnostic investigations.
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| 4. |
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| 5. |
- Anderberg, Leif, et al.
(author)
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Selective diagnostic nerve root block for the evaluation of radicular pain in the multilevel degenerated cervical spine.
- 2006
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In: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 15:6, s. 794-801
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Journal article (peer-reviewed)abstract
- In patients with radiculopathy due to degenerative disease in the cervical spine, surgical outcome is still presenting with moderate results. The preoperative investigations consist of clinical investigation, careful history and most often magnetic resonance imaging (MRI) of the cervical spine. When MRI shows multilevel degeneration, different strategies are used for indicating which nerve root/roots are affected. Some authors use selective diagnostic nerve root blocks (SNRB) for segregating pain mediating nerve roots from non-pain mediators in such patients. The aim of the present study is to assess the ability of transforaminal SNRB to correlate clinical symptoms with MRI findings in patients with cervical radiculopathy and a two-level MRI degeneration, on the same side as the radicular pain. Thirty consecutive patients with cervical radiculopathy and two levels MRI pathology on the same side as the radicular pain were studied with SNRBs at both levels. All patients underwent clinical investigation and neck and arm pain assessment with visual analogue scales (VAS) before and after the blocks. The results from the SNRBs were compared to the clinical findings from neurological investigation as well as the MRI pathology and treatment results. Correlation between SNRB results and the level with most severe degree of MRI degeneration were 60% and correlation between SNRB results and levels decided by neurological deficits/dermatome radicular pain distribution were 28%. Twenty-two of the 30 patients underwent treatment guided by the SNRB results and 18 reported good/excellent outcome results. We conclude that the degree of MRI pathology, neurological investigation and the pain distribution in the arm are not reliable parameters enough when deciding the affected nerve root/roots in patients with cervical radiculopathy and a two-level degenerative disease in the cervical spine. SNRB might be a helpful tool together with clinical findings/history and MRI of the cervical spine when performing preoperative investigations in patients with two or more level of degeneration presenting with radicular pain that can be attributed to the degenerative findings.
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| 6. |
- Anderberg, Leif, et al.
(author)
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Transforaminal steroid injections for the treatment of cervical radiculopathy: a prospective and randomised study.
- 2007
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In: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 16:3, s. 321-328
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Journal article (peer-reviewed)abstract
- Steroid injections are often employed as an alternative treatment for radicular pain in patients with degenerative spinal disorders. Prospective randomised studies of the lumbar spine reveal contradictory results and non-randomised and most often retrospective studies of the cervical spine indicate pain reduction from steroid injections. No prospective randomised study on transforaminal steroid injections for the treatment of radicular pain in the cervical spine focusing on short-term results has been performed. Forty consecutive patients were employed for the study. The inclusion criteria were one-sided cervical radiculopathy with radicular distribution of arm pain distal to the elbow and corresponding significant degenerative pathology of the cervical spine at one or two levels on the same side as the radicular pain and visualised by MRI. A transforaminal technique was used for all injections. A positive response to a diagnostic selective nerve root block at one or two nerve roots was mandatory for all patients. The patients were randomised for treatment with steroids/local anaesthetics or saline/local anaesthetic. Only the neuroradiologist performing the blocks was aware of the content of the injection; all other persons involved in the study were blinded. Follow up was made 3 weeks after the randomised treatment by a clinical investigation and with a questionnaire focusing on the subjective effects from the injections. At follow up, there were no differences in treatment results in the two patient groups. Statistical analysis of the results confirmed the lack of difference in treatment effect. Further studies have to be performed before excluding steroids in such treatment and for evaluating the influence of local anaesthetics on radiculopathy in transforaminal injections.
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| 7. |
- Ansar, Saema, et al.
(author)
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MAPK signaling pathway regulates cerebrovascular receptor expression in human cerebral arteries
- 2013
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In: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 14
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Journal article (peer-reviewed)abstract
- Background: Cerebral ischemia results in enhanced expression of contractile cerebrovascular receptors, such as endothelin type B (ETB), 5-hydroxytryptamine type 1B (5-HT1B), angiotensin II type 1 (AT(1)) and thromboxane (TP) receptors in the cerebral arteries within the ischemic area. The receptor upregulation occurs via activation of the mitogen-activated protein kinases (MAPK) pathway. Previous studies have shown that inhibitors of the MAPK pathway diminished the ischemic area and contractile cerebrovascular receptors after experimental cerebral ischemia. The aim of this study was to examine if the upregulation of contractile cerebrovascular receptors after 48 h of organ culture of human cerebral arteries involves MAPK pathways and if it can be prevented by a MEK1/2 inhibitor. Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into ring segments and incubated for 48 h in the presence or absence of the specific MEK1/2 inhibitor U0126. The vessels were then examined by using in vitro pharmacological methods and protein immunohistochemistry. Results: After organ culture of the cerebral arteries the contractile responses to endothelin (ET)-1, angiotensin (Ang) II and thromboxane (TP) were enhanced in comparison with fresh human arteries. However, 5-carboxamidotryptamine (5-CT) induced decreased contractile responses after organ culture as compared to fresh arteries. Incubation with U0126 diminished the maximum contraction elicited by application of ET-1, Ang II and U46619 in human cerebral arteries. In addition, the MEK1/2 inhibitor decreased the contractile response to 5-CT. Immunohistochemistry revealed that organ culture resulted in increased expression of endothelin ETA, endothelin ETB angiotensin AT(2), 5-hydroxytryptamine 5-HT1B and thromboxane A2 receptors, and elevated levels of activated pERK1/2, all localized to the smooth muscle cells of the cerebral arteries. Co-incubation with U0126 normalized these proteins. Conclusion: The study demonstrated that there is a clear association between human cerebrovascular receptor upregulation via transcription involving activation of the MAPK pathway after organ culture. Inhibition of the MAPK pathways attenuated the vasoconstriction mediated by ET, AT and TP receptors in human cerebral arteries and the enhanced expression of their receptors. The results indicate that MAPK inhibition might be a novel target for treatment of cerebrovascular disorders.
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| 10. |
- Cronqvist, Mats, et al.
(author)
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Diffusion and perfusion MRI in patients with ruptured and unruptured intracranial aneurysms treated by endovascular coiling: complications, procedural results, MR findings and clinical outcome.
- 2005
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In: Neuroradiology. - : Springer Science and Business Media LLC. - 1432-1920 .- 0028-3940. ; 47:11, s. 855-873
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Journal article (peer-reviewed)abstract
- Our purpose was to evaluate treatment safety as well as complications frequency and management in endovascular coiling of intracerebral aneurysms using MR diffusion and perfusion imaging. In this prospective study, 77 MR examinations were performed in conjunction with 43 procedures in 40 patients, 14 patients presented with ruptured and 26 with unruptured aneurysms. Mean time interval between treatment and post-procedure MRI was 29 and 25 h for the ruptured and unruptured aneurysm group, respectively. Peri-procedural complications, including five major events and five minor transient events, occurred in 10/43 procedures (23%), necessitating thrombolytic therapy in two patients and angioplasty in one, all three within the unruptured aneurysm group. Fifty-one new lesions were found on post-treatment DWI and 47 of them were regarded as of ischemic origin. Most lesions were small (< 3 mm), ipsilateral to the treated aneurysm and asymptomatic (37/40 patients). Sixty-seven percent of the lesions were found in the ruptured and 33% in the unruptured aneurysm group. The ischemic lesions did occur more frequently in patients treated for aneurysm of large neck size and according to the remodelling technique. The overall morbidity and mortality rates were 14.6 and 7.3% whereas morbidity and mortality rates related to the technique were only 2.6 and 0%, respectively. Silent embolism seems to be more common than clinically evident and partially related to patient presentation, heparinazation and treatment strategy. The capability to depict early complications and analyse their potential causes by using MR with DWI has been of great importance in our modification and improvement of therapeutic protocols, evaluations and strategies.
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