An alternative method to evaluate lumbar interbody fusion status focusing on position change of screw-rod constructs.

OBJECTIVES: The evaluation of lumbar interbody fusion status is generally subjective and may differ among raters. The authors examined whether the assessment of position change of screw-rod constructs could be an alternative method for the evaluation of fusion status. METHODS: Sixty-three patients undergoing lumbar interbody single-level fusion were retrospectively reviewed. Three-dimensional images of screw-rod constructs were created from baseline CT examination on the day after surgery and follow-up CT examinations (3-5 months, 6-11 months, and ≥ 12 months) and superposed, with position change of screw-rod constructs being evaluated by the distance between the 3-dimensional images at baseline and follow-up. The evaluation was repeated twice to confirm the reproducibility. Fusion status on follow-up CT examinations was assessed by three raters, where inter-rater reliability was evaluated with Fleiss' kappa. The results of the fusion status were classified into fusion and incomplete fusion groups in each timing of follow-up CT examinations, where the amount of position change was compared between the two groups. RESULTS: The evaluation of position change was completely reproducible. The Fleiss' kappa (agreements) was 0.481 (69.4%). The medians of the amount of position change in fusion and incomplete fusion groups were 0.134 mm and 0.158 mm at 3-5 months (p = 0.21), 0.160 mm and 0.190 mm at 6-11 months (p = 0.02), and 0.156 mm and 0.314 mm at ≥ 12 months (p = 0.004). CONCLUSIONS: The assessment of position change of screw-rod constructs at 6 months or more after surgery can be an alternative method for evaluating lumbar interbody fusion status. KEY POINTS: • Lumbar interbody fusion status (satisfactory, incomplete, or failed) is associated with the quantification of position change of screw-rod in this study. • Reference values for the evaluation of position change in identifying interbody fusion status are provided. • Position change of screw-rod could be a supportive method for evaluating interbody fusion status.

A screw position change at an early postoperative stage preceding the subsequent occurrence of screw loosening.

PURPOSE: The authors recently proposed the novel radiologic assessment method to measure chronological screw position changes precisely. The aim of this study was to predict the late occurrence of screw loosening, which was diagnosed by the radiographic lucent zone, by evaluating screw position changes at an early postoperative stage using the novel method. METHODS: Forty-three patients who underwent thoracolumbar screw fixation and follow-up computed tomography (CT) scans on the day, between 1 and 5 weeks, and at more than 6 months after surgery were retrospectively evaluated. Screw images were generated from CT data. Screw position changes were evaluated by superposing screw images on the day and between 1 and 5 weeks after surgery. Screw loosening was diagnosed by the radiographic lucent zone on CT images at 6 months or later post-surgery, and patients were classified into screw loosening and non-loosening groups. The early screw position changes were compared between the two groups. RESULTS: Significant differences in early screw position changes were found between the screw loosening and non-loosening groups in Mann-Whitney U test (p = 0.001). On the receiver operating characteristic (ROC) curve analysis, the area under the ROC curve was 0.791, and the best cutoff value of early screw position change for the prediction of screw loosening was 0.83 mm with a sensitivity of 64.0% and a specificity of 88.9%. CONCLUSION: We calculated a cutoff value of the screw position changes at an early postoperative stage for the prediction of subsequent development of screw loosening with the radiographic lucent zone.

Tenascin-C in brain injuries and edema after subarachnoid hemorrhage: Findings from basic and clinical studies.

Subarachnoid hemorrhage (SAH) by a rupture of cerebral aneurysms remains the most devastating cerebrovascular disease. Early brain injury (EBI) is increasingly recognized to be the primary determinant for poor outcomes, and also considered to cause delayed cerebral ischemia (DCI) after SAH. Both clinical and experimental literatures emphasize the impact of global cerebral edema in EBI as negative prognostic and direct pathological factors. The nature of the global cerebral edema is a mixture of cytotoxic and vasogenic edema, both of which may be caused by post-SAH induction of tenascin-C (TNC) that is an inducible, non-structural, secreted and multifunctional matricellular protein. Experimental SAH induces TNC in brain parenchyma in rats and mice. TNC knockout suppressed EBI in terms of brain edema, blood-brain barrier disruption, neuronal apoptosis and neuroinflammation, associated with the inhibition of post-SAH activation of mitogen-activated protein kinases and nuclear factor-kappa B in mice. In a clinical setting, more severe SAH increases more TNC in cerebrospinal fluid and peripheral blood, which could be a surrogate marker of EBI and predict DCI development and outcomes. In addition, cilostazol, a selective inhibitor of phosphodiesterase type III that is a clinically available anti-platelet agent and is known to suppress TNC induction, dose-dependently inhibited delayed cerebral infarction and improved outcomes in a pilot clinical study. Thus, further studies may facilitate application of TNC as biomarkers for non-invasive diagnosis or assessment of EBI and DCI, and lead to development of a molecular target drug against TNC, contributing to the improvement of post-SAH outcomes.

Toll-Like Receptor 4 and Tenascin-C Signaling in Cerebral Vasospasm and Brain Injuries After Subarachnoid Hemorrhage.

Toll-like receptor 4 (TLR4) is expressed in various cell types in the central nervous system and exerts maximal inflammatory responses among the TLR family members. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of a cerebral aneurysm, and therefore its activation is reasonable as an initial step of cascades to brain injuries after aneurysmal subarachnoid hemorrhage (SAH). TLR4 activation induces tenascin-C (TNC), a representative of matricellular proteins that are a class of inducible, nonstructural, secreted, and multifunctional extracellular matrix glycoproteins. TNC is also an endogenous activator and inducer of TLR4, forming positive feedback mechanisms leading to more activation of the signaling transduction. Our studies have demonstrated that TLR4 as well as TNC are involved in inflammatory reactions, blood-brain barrier disruption, neuronal apoptosis, and cerebral vasospasm after experimental SAH. This article reviews recent understanding of TLR4 and TNC in SAH to suggest that the TLR4-TNC signaling may be an important therapeutic target for post-SAH brain injuries.

Role of Periostin in Early Brain Injury After Subarachnoid Hemorrhage in Mice.

BACKGROUND AND PURPOSE: A matricellular protein tenascin-C is implicated in early brain injury after experimental subarachnoid hemorrhage (SAH). This study first evaluated the role of another matricellular protein periostin and the relationships with tenascin-C in post-SAH early brain injury. METHODS: Wild-type (n=226) and tenascin-C knockout (n=9) C57BL/6 male adult mice underwent sham or filament perforation SAH modeling. Vehicle, anti-periostin antibody, or recombinant periostin was randomly administrated by an intracerebroventricular injection at 30 minutes post-modeling. Neuroscores, SAH grading, brain water content, immunostaining, and Western blotting were blindly evaluated at 24 to 48 hours post-SAH. RESULTS: Periostin was induced in brain capillary endothelial cells and neurons at 24 hours post-SAH. Anti-periostin antibody improved post-SAH neurobehavior, brain edema, and blood-brain barrier disruption associated with downregulation of tenascin-C, inactivation of p38, extracellular signal-related kinase 1/2 and matrix metalloproteinase-9, and subsequent preservation of zona occludens-1. Recombinant periostin aggravated post-SAH brain edema and tenascin-C induction. Tenascin-C knockout prevented post-SAH neurobehavioral impairments and periostin induction. CONCLUSIONS: Periostin may cause post-SAH early brain injury through activating downstream signaling pathways and interacting with tenascin-C, providing a novel approach for the treatment of early brain injury.

Impact of Rehabilitation on Outcomes in Patients With Ischemic Stroke: A Nationwide Retrospective Cohort Study in Japan.

BACKGROUND AND PURPOSE: We aimed to examine the concurrent effects of timing and intensity of rehabilitation on improving activities of daily living (ADL) among patients with ischemic stroke. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database, we retrospectively analyzed consecutive patients with ischemic stroke at admission who received rehabilitation (n=100 719) from April 2012 to March 2014. Early rehabilitation was defined as that starting within 3 days after admission. The average rehabilitation intensity per day was calculated as the total units of rehabilitation during hospitalization divided by the length of hospital stay. A multivariable logistic regression analysis with multiple imputation and an instrumental variable analysis were performed to examine the association of early and intensive rehabilitation with the proportion of improved ADL score. RESULTS: The proportion of improved ADL score was higher in the early and intensive rehabilitation group. The multivariable logistic regression analysis showed that significant improvements in ADL were observed for early rehabilitation (odds ratio: 1.08; 95% confidence interval: 1.04-1.13; P<0.01) and intensive rehabilitation of >5.0 U/d (odds ratio: 1.87; 95% confidence interval: 1.69-2.07; P<0.01). The instrumental variable analysis showed that an increased proportion of improved ADL was associated with early rehabilitation (risk difference: 2.8%; 95% confidence interval: 2.0-3.4%; P<0.001) and intensive rehabilitation (risk difference: 5.6%; 95% confidence interval: 4.6-6.6%; P<0.001). CONCLUSIONS: The present results suggested that early and intensive rehabilitation improved ADL during hospitalization in patients with ischemic stroke.

Vascular Endothelial Growth Factor in Brain Edema Formation After Subarachnoid Hemorrhage.

Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of brain edema formation after experimental subarachnoid hemorrhage (SAH). In this study, we evaluated the effect of anti-VEGF antibody neutralization on brain edema formation after experimental SAH in mice. Mice underwent sham operation or filament puncture SAH and were assigned to sham, SAH + vehicle, or SAH + anti-VEGF antibody groups. Vehicle or anti-VEGF antibody was administrated by an intracerebroventricular injection at 30 min post-SAH. After 24 h of SAH modeling, neurological score was recorded to evaluate neurobehavioral functions, brain water content was calculated to assess the level of brain edema, and immunohistochemistry of immunoglobulin (Ig) G was performed to evaluate the permeability of the blood-brain barrier (BBB). Anti-VEGF antibody significantly ameliorated neurological score and brain edema after SAH compared with the SAH + vehicle group. Immunohistochemistry showed that post-SAH IgG extravasation in brain tissue was suppressed by anti-VEGF antibody. This study suggests that VEGF is involved in brain edema formation after SAH, and that anti-VEGF antibody can decrease BBB permeability, suppress brain edema formation, and improve functional outcome after 24 h of SAH.

The Role of Matricellular Proteins in Brain Edema after Subarachnoid Hemorrhage.

Accumulated evidence suggests that blood-brain barrier disruption or brain edema is an important pathologic manifestation for poor outcome after aneurysmal subarachnoid hemorrhage. Many molecules may be involved, acting simultaneously or at different stages during blood-brain barrier disruption via multiple independent or interconnected signaling pathways. Matricellular protein is a class of nonstructural, secreted, and multifunctional extracellular matrix proteins, which potentially mediates brain edema formation. This study reviews the role of osteopontin and tenascin-C, representatives of matricellular proteins, in the context of brain edema formation after subarachnoid hemorrhage in both clinical and experimental settings.

Aneurysm Organization Effects of Gellan Sulfate Core Platinum Coil with Tenascin-C in a Simulated Clinical Setting and the Possible Mechanism.

BACKGROUND: This study aimed to deliver gellan sulfate core platinum coil with tenascin-C (GSCC-TNC) into rabbit side-wall aneurysms endovascularly and to evaluate the organization effects in a simulated clinical setting. METHODS: Elastase-induced rabbit side-wall aneurysms were randomly coiled via a transfemoral route like clinical settings with platinum coils (PCs), gellan sulfate core platinum coils (GSCCs), or GSCC-TNCs (n = 5, respectively). Aneurysm-occlusion status was evaluated angiographically and histologically at 2 weeks post coiling. As each rabbit coiled aneurysm provided only 2-3 tissue slices due to technical limitations and prevented immunohistochemical evaluations, a PC, GSCC, or GSCC-TNC was randomly implanted in a rat blind-ended model (n = 3, respectively) and the organization effects were immunohistochemically evaluated for expressions of tenascin-C (TNC), transforming growth factor-beta (TGF-ß), and matrix metalloproteinase-9 (MMP-9) 2 weeks later. RESULTS: Coil handling was similar among the 3 kinds of coils. GSCCs showed a significantly higher ratio of organized area to the aneurysmal cavity than PCs, but GSCC-TNCs had the greatest organization-promoting effects on aneurysms (the ratio of organized area/aneurysmal luminal area: PC, 17.9 ± 7.1%; GSCC, 54.2 ± 18.3%; GSCC-TNC, 82.5 ± 5.8%). GSCC-TNCs had intense immunoreactivities for TNC, TGF-ß, and MMP-9 in the organized thrombosis and tunica media. GSCCs also showed intense immunoreactivities for TNC, TGF-ß, and MMP-9, although the extent was less than GSCC-TNCs. The immunoreactivities were hardly found in unorganized thrombus and the tunica media of aneurysm wall in the PC group. CONCLUSIONS: This study first showed that GSCC-TNCs promote intra-aneurysmal clot organization in simulated clinical settings using rabbits possibly through the TGF-ß and MMP-9 upregulation.

Effects of tenascin-C on early brain injury after subarachnoid hemorrhage in rats.

BACKGROUND AND PURPOSE: We previously reported that tenascin-C (TNC), a matricellular protein, was involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), but the role of TNC in early brain injury (EBI) is unknown. This study assessed whether inhibition of TNC upregulation in brain by imatinib mesylate (imatinib), an inhibitor of the tyrosine kinases of platelet-derived growth factor receptors, prevents EBI after experimental SAH. METHODS: Rats were assigned to sham, SAH plus vehicle, and SAH plus imatinib groups (n = 4 per group). Imatinib (50 mg/kg body weight) was administered intraperitoneally to rats undergoing SAH by endovascular perforation, and EBI was evaluated using terminal deoxynucleotidyl transferase-mediated uridine 5-triphosphate-biotin nick end-labeling staining at 24 h after SAH. Imatinib-treated SAH rats were also treated by a cisternal injection of recombinant TNC. RESULTS: SAH upregulated TNC and caused EBI. Imatinib treatment suppressed both TNC upregulation and EBI at 24 h. Recombinant TNC reinduced EBI in imatinib-treated SAH rats. CONCLUSIONS: TNC may be involved in the pathogenesis of EBI after SAH.

Tenascin-C is a possible mediator between initial brain injury and vasospasm-related and -unrelated delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Tenascin-C (TNC), a matricellular protein, exerts diverse functions, including tissue remodeling and apoptosis, and is induced in cerebrospinal fluid (CSF) after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to examine the relationships among CSF TNC levels, initial brain injury, delayed cerebral ischemia (DCI), and vasospasm after SAH. METHODS: CSF TNC levels were measured in 30 patients with aneurysmal SAH of Fisher computed tomography (CT) group III who were treated microsurgically or endovascularly with CSF drainage within 24 h of SAH. Admission World Federation of Neurosurgical Societies (WFNS) grade was supposed to indicate the severity of initial brain injury. Cerebral vasospasm was defined as narrowed (≥ 25 %) cerebral arteries demonstrated by angiography. DCI was defined as any neurological deterioration presumed related to ischemia that persisted for ≥ 1 h. RESULTS: Higher CSF TNC levels were correlated with worse admission WFNS grades. Vasospasm was aggravated with higher TNC levels. DCI occurred regardless of the degree of vasospasm but was associated with TNC induction. Multivariate analyses showed that higher TNC levels and vasospasm were independent predictors of DCI occurrence. CONCLUSIONS: SAH (initial brain injury) that is more severe induces more TNC, which may cause the subsequent development of both vasospasm and vasospasm-unrelated secondary brain injury, leading to DCI.

Vasoconstrictive effect of tenascin-C on cerebral arteries in rats.

BACKGROUND AND PURPOSE: The authors have reported that tenascin-C (TNC), a matricellular protein, is induced after subarachnoid hemorrhage (SAH), associated with cerebral vasospasm. In this study, we examined whether TNC alone causes cerebral vasospasm-like constriction of the intracranial internal carotid arteries (ICAs) in rats, focusing on the p38 mitogen-activated protein kinase (MAPK)-mediated mechanisms. METHODS: First, we injected 10 µg of TNC into the cisterna magna of healthy rats and studied morphologically whether TNC caused constriction of the left ICA at 24-72 h after administration. Second, we examined the effect of SB203580 (a p38 MAPK inhibitor) on the vessel diameter of the left ICA in healthy rats at 24 h. Third, we evaluated the effect of SB203580 on TNC-induced constriction of the left ICA in healthy rats at 24 h. RESULTS: TNC significantly induced cerebral vasospasm-like angiographic constriction of the left ICAs, which continued at least for 72 h. SB203580 itself had no effect on the diameter of normal ICAs, but abolished the TNC-induced vasoconstrictive effect on the left ICA. CONCLUSION: These findings show that TNC causes left ICA constriction via activation of p38 MAPK, resembling post-SAH vasospasm, and suggest the possible involvement of TNC in the pathogenesis of cerebral vasospasm.

A novel approach to evaluation of lumbar bone density using Hounsfield units in volume of interest on computed tomography imaging.

OBJECTIVE: The purpose of this retrospective study was to evaluate the relationship between bone mineral density (BMD), as assessed with dual-energy x-ray absorptiometry (DEXA), and Hounsfield units (HU) measured in volumes of interest (VOIs) and regions of interest (ROIs) on lumbar spine CT. METHODS: A retrospective analysis was performed on data of lumbar vertebrae obtained from patients who underwent both DEXA and lumbar spine CT scan within a 6-month period. Vertebrae with a history of compression fracture, infectious spondylitis, cement reinforcement, or lumbar surgery were excluded. HU measurements were performed in the VOI and ROI (midaxial, midcoronal, and midsagittal sections) with CT, whereas BMD was assessed with DEXA. Statistical analyses, including correlation assessments and receiver operating characteristic (ROC) curve analyses, were performed. RESULTS: This analysis included 712 lumbar vertebrae, with a median patient age of 72.0 years. BMD values and HU measurements in the VOI increased sequentially from L1 to L4, whereas HU values in the ROI did not show a consistent pattern. HU values in the VOI consistently showed a stronger correlation with BMD than those in the ROI. ROC analysis revealed patient-level cutoff values for the diagnosis of osteoporosis at different lumbar vertebral levels with high sensitivity and specificity, as well as an excellent area under the curve. CONCLUSIONS: This is the first study to introduce a novel approach using the HU value in the VOI to assess bone health at the lumbar spine. There is a strong correlation between the HU value in the VOI and BMD, and the HU value in the VOI can be used to predict osteoporosis.

Temporal Shape Changes of Pedicle screw-rod Constructs After Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: To examine the shape change of screw-rod constructs over time following short-segment lumbar interbody fusion and to clarify its relationship to clinical characteristics. SUMMARY OF BACKGROUND DATA: No study has focused on the shape change of screw-rod constructs after short-segment fusion and its clinical implications. METHODS: One hundred and eight patients who had single-level lumbar interbody fusion with pedicle screws and cages were enrolled. Three-dimensional (3D) images of screw-rod constructs were generated from baseline CT on the day after surgery and follow-up CT, and were superposed on the right and left side, respectively, using the iterative closest point algorithm. The shape change was quantitatively assessed by computing the median distance between the 3D images, which was defined as the shape change value. Among the five time-course categories of follow-up CT (≤1 month, 2-3 months, 4-6 months, 7-12 months, ≥13 months), the shape change values were compared. The relationships between the shape change values and clinical characteristics, such as age, CT-derived vertebral bone mineral density, screw and rod materials, and postoperative interbody fusion status, cage subsidence, and screw loosening, were evaluated. RESULTS: A total of 237 follow-up CTs were included (≤1 month [34 scans], 2-3 months [33 scans], 4-6 months [80 scans], 7-12 months [48 scans], ≥13 months [42 scans]) because many patients underwent multiple follow-up CTs. There were significant differences in shape change values among the time-course categories (P<0.001 in Kruskal-Wallis test). Most shape changes occurred within 6 months postoperatively, with no significant changes observed at 7 months or more. There were no significant relationships between the shape change values and each clinical characteristic. CONCLUSION: The temporal shape changes of screw-rod constructs following short-segment lumbar interbody fusion progressed up to 6 months after surgery but not significantly thereafter.

Cilostazol May Improve Outcomes Even in Patients with Aneurysmal Subarachnoid Hemorrhage Aged 75 Years and Older: Multicenter Cohort Study and Propensity Score-Matched Analyses.

BACKGROUND: The opportunities to treat elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) are increasing globally, but the outcome remains poor. This study seeks to investigate treatment-related factors that can modify functional outcomes in patients with aSAH aged ≥75 years. METHODS: A total of 202 patients with aSAH aged ≥75 years prospectively enrolled in 9 primary stroke centers from 2013 to 2021 were retrospectively analyzed. Clinical variables including treatments for hydrocephalus, angiographic vasospasm, and delayed cerebral ischemia were compared between patients with good (modified Rankin Scale [mRS] score 0-2) and poor (mRS score 3-6) outcomes at 90 days from onset, followed by multivariate analyses to find independent outcome determinants. A modifiable treatment-related variable was evaluated after propensity score matching with adjustments for age, sex, pre-onset mRS score, aSAH severity, and treatment modality. RESULTS: More than half of patients showed World Federation of Neurological Societies grades IV-V on admission. Univariate analyses showed that advanced age, worse pre-onset mRS score, more severe neurologic status on admission, higher modified Fisher grade on admission computed tomography scans, and acute and chronic hydrocephalus were associated with poor outcomes. In contrast, administration of a phosphodiesterase type III inhibitor, cilostazol, was associated with good outcomes in both univariate (P = 0.036) and multivariate analyses (adjusted odds ratio, 0.305; 95% confidence interval, 0.097-0.955; P = 0.042). Propensity score matching analyses showed that patients treated with cilostazol had better outcomes (P = 0.016) with fewer incidences of delayed cerebral infarction (P = 0.008). CONCLUSIONS: Even in patients with aSAH aged ≥75 years, cilostazol administration may lead to better outcomes by suppressing the development of delayed cerebral infarction.

Tenascin-C induces prolonged constriction of cerebral arteries in rats.

Tenascin-C (TNC), a matricellular protein, is induced in association with cerebral vasospasm after subarachnoid hemorrhage. The aim of this study was to assess the vasoconstrictive effects of TNC and its mechanisms of action on cerebral arteries in vivo. Two dosages (1 and 10µg) of TNC were administered intracisternally to healthy rats, and the effects were evaluated by neurobehavioral tests and India-ink angiography at 24, 48, and 72h after the administration. Western blotting and immunohistochemistry were performed to explore the underlying mechanisms on constricted cerebral arteries after 24h. The effects of toll-like receptor 4 (TLR4) antagonists (LPS-RS), c-Jun N-terminal kinase (JNK), and p38 inhibitors (SP600125 and SB203580) on TNC-induced vasoconstriction were evaluated at 24h. Higher dosages of TNC induced more severe cerebral arterial constriction, which continued for more than 72h. TNC administration also upregulated TLR4, and activated JNK and p38 in the smooth muscle cell layer of the constricted cerebral artery. LPS-RS blocked TNC-induced TLR4 upregulation, JNK and p38 activation, and vasoconstrictive effects. SP600125 and SB203580 abolished TNC-induced TLR4 upregulation and vasoconstrictive effects. TNC may cause prolonged cerebral arterial constriction via TLR4 and activation of JNK and p38, which may upregulate TLR4. These findings suggest that TNC causes cerebral vasospasm and provides a novel therapeutic approach against it.

Matricellular protein: a new player in cerebral vasospasm following subarachnoid hemorrhage.

INTRODUCTION: Matricellular protein (MCP) is a class of nonstructural and secreted extracellular matrix proteins that exert diverse functions, but its role in vascular smooth muscle contraction has not been investigated. MATERIAL AND METHODS: First, rat subarachnoid hemorrhage (SAH) models were produced by endovascular perforation and examined for tenascin-C (TNC) and osteopontin (OPN) induction (representatives of MCPs) in vasospastic cerebral arteries using immunostaining. Second, recombinant TNC (r-TNC), recombinant OPN (r-OPN), or both were injected into a cisterna magna in healthy rats, and the effects on the diameter of basilar arteries were determined using India ink angiography. RESULTS: In SAH rats, TNC immunoreactivity was markedly induced in the smooth muscle cell layers of spastic cerebral arteries on day 1 but not in control animals. The TNC immunoreactivity decreased on day 3 as vasospasm improved: OPN immunoreactivity, on the other hand, was more induced in the arterial wall on day 3. r-TNC injections caused prolonged contractions of rat basilar arteries, which were reversed by r-OPN, although r-OPN itself had no effect on the vessel diameter. CONCLUSIONS: MCPs, including TNC and OPN, may contribute to the pathophysiology of cerebral vasospasm and provide a novel therapeutic approach against it.

Role of platelet-derived growth factor in cerebral vasospasm after subarachnoid hemorrhage in rats.

BACKGROUND AND PURPOSE: The role of platelet-derived growth factor (PDGF) remains unknown in cerebral vasospasm after subarachnoid hemorrhage (SAH). In this study, we examined the effects of PDGF receptor (PDGFR) inactivation on cerebral vasospasm in the endovascular perforation model of SAH in rats. METHODS: Rats were assigned to sham, SAH plus vehicle, and SAH plus imatinib mesylate (imatinib) groups (n = 4 per group). Imatinib (50 mg/kg body weight), an inhibitor of the tyrosine kinases of PDGFR, or vehicle was administered intraperitoneally 30 min post-SAH. Vasospasm was evaluated in the left (perforation-sided) internal carotid artery by means of neurobehavioral tests, India ink angiography, and immunohistochemistry at 24 h after SAH. RESULTS: Imatinib significantly inhibited post-SAH PDGFR activation in the left internal carotid artery, in which vasospasm was significantly prevented. Animal's neurobehavior also showed a tendency to improve by imatinib treatment. CONCLUSIONS: PDGF may play an important role in the pathogenesis of vasospasm after SAH.

Development of new measurement system of thoracic excursion with biofeedback: reliability and validity.

BACKGROUND: Respiratory rehabilitation reduces breathlessness from patient with respiratory dysfunction. Chest expansion score, which represents the circumference magnitude of the thoracic cage, is used for a target when treating patients with respiratory disease. However, it is often difficult for patients to understand the changes in the respiratory status and be motivated for therapy continuously. We developed a new measurement system with biofeedback named BREATH which shows chest expansion scores in real time. The purpose of this study was to determine the reliability and validity of the novel system in advance of clinical application. METHODS: Three evaluators measured chest expansion in 33 healthy individuals using tape measure, which is used for the measurement traditionally, and BREATH. The wire for BREATH system was threaded over the thoracic continuously and the data was recorded automatically; whereas the tape was winded and measured each maximal expiration and inspiration timing by evaluator. All participants were performed both measurement simultaneously for three times during deep breath. In this study, we studied chest expansion score without using biofeedback data of BREATH to check the validity of the result. To confirm intra- and inter-evaluator reliability, we computed intra-class correlations (ICCs). We used Pearson's correlation coefficient to evaluate the validity of measurement result by BREATH with reference to the tape measure results. RESULTS: The average (standard deviation) chest expansion scores for all, men and women by the tape measure were 5.53 (1.88), 6.40 (1.69) and 5.22 (1.39) cm, respectively, and those by BREATH were 3.89 (2.04), 4.36 (1.83) and 2.89 (1.66) cm, respectively. ICC within and among the three evaluators for BREATH and the tape measure were 0.90-0.94 and 0.85-0.94 and 0.85 and 0.82, respectively. The correlation coefficient between the two methods was 0.76-0.87. CONCLUSION: The novel measurement system, BREATH, has high intra- and inter-evaluator reliabilities and validity; therefore it can lead us more effective respiratory exercise. Using its biofeedback data, this system may help patients with respiratory disease to do exercises more efficiently and clinicians to assess the respiratory exercise more accurately.

Plasma SPARC Elevation in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Matricellular proteins have been implicated in pathologies after subarachnoid hemorrhage (SAH). To find a new therapeutic molecular target, the present study aimed to clarify the relationships between serially measured plasma levels of a matricellular protein, secreted protein acidic and rich in cysteine (SPARC), and delayed cerebral ischemia (DCI) in 117 consecutive aneurysmal SAH patients with admission World Federation of Neurological Surgeons (WFNS) grades I-III. DCI developed in 25 patients with higher incidences of past history of hypertension and dyslipidemia, preoperative WFNS grade III, modified Fisher grade 4, spinal drainage, and angiographic vasospasm. Plasma SPARC levels were increased after SAH, and significantly higher in patients with than without DCI at days 7-9, and in patients with VASOGRADE-Yellow compared with VASOGRADE-Green at days 1-3 and 7-9. However, there were no relationships between plasma SPARC levels and angiographic vasospasm. Receiver-operating characteristic curves differentiating DCI from no DCI determined the cut-off value of plasma SPARC ≥ 82.1 ng/ml at days 7 - 9 (sensitivity, 0.800; specificity, 0.533; and area under the curve, 0.708), which was found to be an independent determinant of DCI development in multivariate analyses. This is the first study to show that SPARC is upregulated in peripheral blood after SAH, and that SPARC may be involved in the development of DCI without angiographic vasospasm in a clinical setting.