Prevalence of C7 level anomalies at the C7 level: an important landmark for cervical nerve ultrasonography.

BACKGROUND: Recently, various examination and intervention techniques using cervical nerve ultrasonography have been developed. The specific shapes of the C7 transverse process and vertebral artery in front of the C7 transverse process have become landmarks. PURPOSE: To determine the prevalence of anomalies and anomalous vertebral artery entrances at the C7 transverse process. MATERIAL AND METHODS: The records of patients who underwent plain or contrast-enhanced neck or cervical spine computed tomography (CT) were reviewed. The examinations were scored for the anomalous presence of anterior tubercles or cervical ribs as well as vertebral artery entrances in the C7 transverse process. The prevalence of anomalies was compared based on patient sex and age. RESULTS: Evaluating the examinations from 2067 patients (1046 men; 1021 women), 1% of patients exhibited an anomalous presence of anterior tubercles, and 0.3% of patients displayed cervical ribs at the C7 transverse process. The prevalence of anomalies process was significantly higher in men aged less than 40 years than in older men (P < 0.001), whereas the prevalence was not higher in women aged less than 40 years than in older women. The prevalence of vertebral artery entry into the C7 transverse foramen was 0.6%. CONCLUSION: Although an anomalous vertebral artery entry into the C7 transverse foramen was rare, the prevalence of an anomaly at the C7 transverse process was higher in men aged less than 40 years. Therefore, we recommend performing CT in younger men before cervical nerve ultrasonographic intervention to avoid misinterpretations at the cervical level.

Diagnostic accuracy of multifidus muscle spontaneous activity by needle electromyography for the detection of lumbar foraminal and lateral exit-zone stenosis.

PURPOSE: The medial branch of the posterior ramus of the lumbar spinal nerve is well known to be innervated independently and to end in the multifidus muscle without anastomosis. This prospective cohort study aimed to determine the diagnostic specificity and sensitivity of multifidus muscle denervation (MMD) by needle electromyography (N-EMG) for lumbar foraminal and lateral exit-zone stenosis (LF/LEZS). METHODS: We enrolled 61 consecutive patients experiencing unilateral dysesthesia and/or leg pain in the L4 or L5 regions with suspicious LF/LEZS. The Japanese Orthopedic Association (JOA) score, Visual Analog Scale (VAS) for leg pain, and N-EMG were examined. In this study protocol, all patients received at least 3 months of conservative therapy. Surgery was performed on patients who experienced less than 50% VAS pain relief compared with their initial score after confirming the responsible level by lumbar nerve root block. The specificity of N-EMG was the proportion of patients who improved with conservative therapies (non-surgery) after 3 months. The sensitivity of N-EMG was the proportion of patients who improved with surgical therapies (surgery) after more than 12 months. RESULTS: Twenty-three patients underwent surgery. The initial lower JOA, positive Kemp test and motor weakness were significantly higher in the surgery group. The MMD by N-EMG indicated that 34 of 38 patients were negative in the non-surgery group. In the surgery group, 21 of 23 patients were positive. The diagnostic sensitivity and specificity were 91.3 and 92.1%, respectively. CONCLUSIONS: Needle electromyography is a simple and available additional method for the diagnosis of LF/LEZS.

Expression of suppressor of cytokine signaling 3 in cerebrospinal fluid after subarachnoid hemorrhage.

BACKGROUND: IL-6 is a proinflammatory cytokine reported to play an important role in the induction of cerebral vasospasm after subarachnoid hemorrhage (SAH). Suppressor of cytokine signaling 3 (SOCS3) is known to act as an inhibitor of signal transduction of IL-6. However, there have been no reports on the expression of SOCS3 in cerebrospinal fluid (CSF) after SAH. FINDINGS: The concentration of IL-6 was measured serially up until day 10, in CSF of eight patients with SAH. CSF samples obtained from patients suffering from an unruptured aneurysm were used as controls. The expression of SOCS3 in CSF was further examined by immunoprecipitation methods. Concentrations of IL-6 in CSF increased immediately after the onset of SAH and remained chronically elevated over control values. SOCS3 was significantly expressed in CSF on days 1 to 3 after SAH. CONCLUSIONS: Our findings suggest that SOCS3 regulates IL-6 signaling as an antagonist in CSF, immediately following SAH. As the expression of SOCS3 decreases after day 5, IL-6 signals might then be more easily transmitted, presumably resulting in cerebral vasospasm.

Platelet-derived Growth Factor Activates Pericytes in the Microvessels of Chronic Subdural Hematoma Outer Membranes.

Angiogenesis is one of the growth mechanisms of chronic subdural hematoma (CSDH). Pericytes have been implicated in the capillary sprouting during angiogenesis and are involved in brain ischemia and diabetic retinopathy. This study examined the pericyte expressions in CSDH outer membranes obtained during trepanation surgery. Eight samples of CSDH outer membranes and 35 samples of CSDH fluid were included. NG2, N-cadherin, VE-cadherin, Tie-2, endothelial nitric oxide synthase (eNOS), platelet-derived growth factor (PDGF) receptor-ß (PDGFR-ß), a well-known marker of pericytes, phosphorylated PDGFR-ß at Tyr751, and ß-actin expressions, were examined using western blot analysis. PDGFR-ß, N-cadherin, and Tie-2 expression levels were also examined using immunohistochemistry. The concentrations of PDGF-BB in CSDH fluid samples were measured using enzyme-linked immunosorbent assay kits. NG2, N-cadherin, VE-cadherin, Tie-2, eNOS, PDGFR-ß, and eNOS expressions in CSDH outer membranes were confirmed in all cases. Furthermore, phosphorylated PDGFR-ß at Tyr751 was also detected. In addition, PDGFR-ß, N-cadherin, and Tie-2 expressions were localized to the endothelial cells of the vessels within CSDH outer membranes by immunohistochemistry. The concentration of PDGF-BB in CSDH fluids was significantly higher than that in cerebrospinal fluid. These findings indicate that PDGF activates pericytes in the microvessels of CSDH outer membranes and suggest that pericytes are crucial in CSDH angiogenesis through the PDGF/PDGFR-ß signaling pathway.

Angiogenesis in the Outer Membrane of Chronic Subdural Hematomas through Thrombin-Cleaved Osteopontin and the Integrin α9 and Integrin ß1 Signaling Pathways.

BACKGROUND: A chronic subdural hematoma (CSDH) is considered to be an inflammatory and angiogenic disease. The CSDH outer membrane, which contains inflammatory cells, plays an important role in CSDH development. Osteopontin (OPN) is an extracellular matrix protein that is cleaved by thrombin, generating the N-terminal half of OPN, which is prominently involved in integrin signal transduction. We explored the expression of the N-terminal half of OPN in CSDH fluid and the expression of integrins α9 and ß1 and the downstream components of the angiogenic signaling pathways in the outer membrane of CSDHs. METHODS: Twenty samples of CSDH fluid and eight samples of CSDH outer membrane were collected from patients suffering from CSDHs. The concentrations of the N-terminal half of OPN in CSDH fluid samples were measured using ELISA kits. The expression levels of integrins α9 and ß1, vinculin, talin-1, focal adhesion kinase (FAK), paxillin, α-actin, Src and ß-actin were examined by Western blot analysis. The expression levels of integrins α9 and ß1, FAK and paxillin were also examined by immunohistochemistry. We investigated whether CSDH fluid could activate FAK in cultured endothelial cells in vitro. RESULTS: The concentration of the N-terminal half of OPN in CSDH fluid was significantly higher than that in the serum. Western blot analysis confirmed the presence of these molecules. In addition, integrins α9 and ß1, FAK and paxillin were localized in the endothelial cells of vessels within the CSDH outer membrane. FAK was significantly phosphorylated immediately after treatment with CSDH fluid. CONCLUSION: Our data suggest that the N-terminal half of OPN in CSDH fluid promotes neovascularization in endothelial cells through integrins α9 and ß1. The N-terminal half of OPN, which is part of the extracellular matrix, plays a critical role in the promotion of CSDHs.

Fructose induces tubulointerstitial injury in the kidney of mice.

Fructose induces several kinds of human metabolic disorders; however, information regarding fructose-induced kidney injury is still limited. This study examined fructose-induced kidney injury in mice and clarified the differential susceptibility of three mouse strains: C57Bl/6J, CBA/JN and DBA/2N. In this study all mice were fed with an equal calorie count for sixteen weeks to remove the influence of total energy intake from metabolic effects by fructose-feeding. Only DBA/2N mice, but not C57Bl/6J and CBA/JN mice, fed with fructose displayed tubulointerstitial fibrosis localized on the outer cortex of the kidney together with the increase of mRNA expression of Kim1 and Ngal in the absence of distinct glomerular lesions and albuminuria - decidedly different from diabetic nephropathy. In time-course study of DBA/2N mice fed with fructose diet, the inflammation and fibrosis in the outer cortex of the kidney were enhancing after eight weeks, in parallel with the accumulation of oxidative stress. This progression of renal damage in DBA/2N mice was accompanied with increasing mRNA expression of GLUT5. These results suggest that the responsiveness of GLUT5 expression to fructose at the kidney is one of pivotal roles for the progression of fructose-induced kidney injury.

Double Crush Syndrome of the Lower Limb in L5 Radiculopathy and Peroneal Neuropathy: A Case Report.

Double crush syndrome (DCS) is a clinical condition involving impingement of the spinal and peripheral nerves. DCS of the lower limbs has been recognized; however, no detailed reports have been published. Herein, we report a rare case of the coexistence of L5 radiculopathy and peroneal nerve entrapment neuropathy. The patient suffered from pain in the left lower leg and left foot combined with muscle weakness in the left leg without a Tinel-like sign in the peroneal tunnel area. MRI showed a deficit in the left L5 nerve root sleeve, and X-ray imaging revealed L5 spondylolysis. Lumbar fusion surgery was performed at L5-S1. Subsequently, the patient's symptoms were partially improved, but the pain and toe and ankle motor weakness persisted. In addition, a Tinel-like sign appeared at the entrapment point of the peroneal nerve. The entrapped peroneal nerve was decompressed, and the patient's symptoms improved. The patient had L5 radiculopathy owing to the improvement in his symptoms in the upper leg before and after lumbar surgery. It is unclear why no Tinel-like sign was detected before the first surgery, but we hypothesized that L5 nerve disorder may mask the symptoms triggered by compression of the peroneal nerve due to the complex pathology of DCS and dynamic factors. Distinguishing between radiculopathy and relative peripheral neuropathy should always be a consideration. DCS may mask characteristic symptoms, and it is important to carefully follow up the patient to detect changes in his or her condition.

Endotracheal Tube Obstruction Experienced during an Anterior Cervical Discectomy and Fusion.

During anterior cervical discectomy and fusion (ACDF), endotracheal tube difficulties are anticipated at the operative level but are unexpected elsewhere in the airway. We report the case of a 66-year-old woman who underwent C4/C5 ACDF to treat adjacent segment disease following a previous anterior cervical fixation surgery. Shortly after her lower jaw was elevated and the fusion cage was inserted, a rise in airway pressure was observed, indicating impaired breathing. Subsequent examination revealed a bent endotracheal tube in the oral cavity as the cause of the respiratory impairment. During anterior cervical surgery, elevating the lower jaw can cause the tongue root to press against the endotracheal tube. Reinforced endotracheal tubes, with a spiral-wound wire in the inner wall, would effectively prevent this issue. In the unlikely event of impaired breathing during such an operation, the oral cavity should be inspected for confirmation of an open airway.

Spinal Epidural Hematoma Associated with Epidural Metastasis After Minor Trauma.

BACKGROUND: Spinal epidural hematoma associated with epidural metastasis is very rare. Epidural hematoma is unusual in itself, and metastatic epidural tumors do not commonly occur. CASE DESCRIPTION: A 76-year-old man with a medical history of untreated stage III rectal cancer and chronic obstructive pulmonary disease underwent emergency spine surgery for acute development of severe quadriplegia due to cervical epidural hematoma after minor indirect trauma. Hemorrhagic lesions, such as yellow ligaments, were accompanied by hematomas that adhered to the dura mater and were confirmed on pathology to be small cell carcinoma. Some nodules were detected in the right pulmonary hilar lesion and pleural lesion on computed tomography, and stage IV small cell carcinoma was diagnosed. CONCLUSIONS: To our knowledge, spinal epidural hematoma accompanied by epidural metastasis has not previously been reported. We hypothesized that tissue invasion of malignant neoplasms may cause hemorrhagic conditions. The presence of a tumor should therefore be considered in the differential diagnosis of cases of epidural hematoma.

Growing skull fracture with an atypical mechanism: a case report.

Growing skull fractures (GSFs) are well-known but rare causes of pediatric head trauma. They generally occur several months after a head injury, and the main lesion is located under the periosteum. We herein report a case involving a 3-month-old boy with GSF that developed by a different mechanism than previously considered. It developed 18 days after the head injury. A large mass containing cerebrospinal fluid and brain tissue was present within the periosteum. A good outcome was obtained with early strategic surgery. Injury to the inner layer of the periosteum and sudden increase in intracranial pressure might be related to GSF in this case.

Expression of Autophagy Signaling Molecules in the Outer Membranes of Chronic Subdural Hematomas.

Chronic subdural hematoma (CSDH) is fundamentally treatable, although it sometimes recurs. We observed, however, several cases of spontaneous resolution of CSDH outer membranes, even in a trabecular type of CSDH, after a trepanation surgical procedure. In this study, we examined the expression of molecules of the autophagy signaling pathway in CSDH outer membranes. Eight patients whose outer membranes were obtained successfully during trepanation were included in this study. By Western blot analysis, we examined the expression of mammalian target of rapamycin (mTOR); GßL; UNC-51-like kinase-1 (ULK1); Beclin-1; autophagy-related genes (Atg) 3, 5, 7, 12, 13, and 16L1ß,α; the autophagy marker Light Chain3A/B (LC3A/B); and ß-actin, which constitute the autophagy signaling pathway. The expression levels of Beclin-1, Atg12, and LC3A/B were also examined by immunohistochemistry. Almost all of these molecules could be detected in all samples. Beclin-1, Atg12, and LC3A/B were found to be localized in the endothelial cells of vessels and fibroblasts in CSDH. We detected molecules of the autophagy signaling pathway in CSDH outer membranes. Autophagy contributes to the tissue homeostatic process, maintaining cellular integrity by clearing debris. Our data suggest that autophagy might play an important role in the spontaneous resolution of CSDH. Therefore, these molecules may be novel therapeutic targets for the treatment of those with CSDH.

Reliability of an Intraoperative Radiographic Anteroposterior View of the Spinal Midline for Detection of Pedicle Screws Breaching the Medial Pedicle Wall in the Thoracic, Lumbar, and Sacral Spine.

OBJECTIVE: The purpose of this study was to determine the sensitivity and specificity of using the spinal midline (M line) on a radiographic anteroposterior (AP) view for detecting pedicle screws (PSs) breaching the medial pedicle wall. METHODS: We retrospectively reviewed 145 patients who underwent fusion surgery using PSs between January 2006 and May 2017. We defined the M line as a line that connected the upper and lower spinous processes through the fixed vertebrae. The M line was positive if the tip of the PS crossed the M line. The reference standard was a computed tomography scan. The reliability of the M line was examined. RESULTS: The subjects included 145 patients (70 men and 75 women; mean age, 63.4 years). A total of 599 PSs were examined. Most cases were because of spondylolisthesis (66.9%). Most screws were inserted at a lower lumber level (77.6%). Analysis of the diagnostic accuracy of the M line yielded a sensitivity of 74.1% and a specificity of 95.3%. In addition, the positive predictive value of the M line was 42.6%, and the negative predictive value of the M line was 98.7%. CONCLUSIONS: Assessment of the M line via an intraoperative radiographic AP view is a simple, readily available, complementary method for detecting PSs that have breached the medial pedicle wall in the thoracic, lumbar, and sacral spine. In particular, the M line has a strong negative predictive value, which is much more meaningful.

Expressions of Eotaxin-3, Interleukin-5, and Eosinophil-Derived Neurotoxin in Chronic Subdural Hematoma Fluids.

Eosinophils induce inflammation by releasing cytokines and cytotoxic granule proteins. Infiltration of eosinophilic granulocytes occurs in the outer membrane of chronic subdural hematomas (CSDHs). Eosinophils play an important role in the growth of CSDHs. However, the manner in which eosinophils accumulate within CSDH fluid remains undetermined. In the current study, we assessed the expression of eosinophil chemoattractants in CSDH fluids according to growth stage of CSDHs and examined the correlation between the two. CSDH fluids were obtained from 38 patients during trepanation surgery. Ecalectin, eotaxin-3, interleukin-5 (IL-5), and eosinophil-derived neurotoxin (EDN) concentrations were measured using enzyme-linked immunosorbent assay kits. For use as controls, serum samples were collected from 5 healthy adults, and cerebrospinal fluid (CSF) samples were collected from 5 adults with unruptured aneurysms. The percentage of eosinophils (%eosinophil) in CSDH fluids was calculated using Giemsa staining. Concentrations of ecalectin, eotaxin-3, IL-5, and EDN were nearly equivalent in serum and CSF samples; however, their concentrations were high in CSDH fluids. In particular, ecalectin and EDN levels in CSDH fluids were significantly higher than those in serum and CSF. Levels of eotaxin-3, IL-5, EDN, and %eosinophil were significantly higher in laminar type of CSDH, whereas that of ecalectin was not. The correlations between eotaxin-3 and IL-5, IL-5 and EDN, and EDN and %eosinophil were statistically significant (p < 0.01). Our data suggest that eotaxin-3 is a chemoattractant of eosinophils. IL-5 induces the activation of eosinophils subsequent to degranulation of EDN into CSDH fluids. These factors may serve as novel therapeutic targets for managing CSDH.

Posterior inferior cerebellar artery with an extradural origin from the V3 segment: higher incidence on the nondominant vertebral artery.

OBJECTIVE The posterior inferior cerebellar artery (PICA) and the vertebral artery (VA) often exhibit anatomical variations at the craniovertebral junction (CVJ). An example of this is the PICA originating extradurally from the V3 segment of the VA. To date, some cadaveric investigations have been reported, but the incidence and relationship of this variation to the VA and the atlas as observed on clinical imaging have not been discussed. This study evaluated the prevalence of PICAs originating from the V3 on CT scanning. Other variations of the atlas and VA were also analyzed. METHODS CT images from a series of 153 patients who underwent 3D CT angiography (CTA) were analyzed, and variations of the PICA, VA, and atlas were investigated. RESULTS A total of 142 patients (284 sides) were analyzed; 11 patients (7.2%) were excluded due to poor image quality. The most common VA variation was the PICA originating from V3 (9.5% of 284 sides), which was more frequently observed on the nondominant VA than the dominant VA (22.5% vs 6.25%, p = 0.0005). A VA with a PICA end was identified in 4 sides (1.4%), which is the same incidence as observed in the persistent first intersegmental VA (1.4%). VA fenestration was only found in 1 side (0.35%). Regarding the atlas, ponticulus posticus was observed in 24 sides (8.5%). There was no relationship between the incidence of ponticulus posticus and the variations of the VA. CONCLUSIONS A PICA originating from V3 was the most common VA variation at the CVJ and was more common on the nondominant VA. Three-dimensional CTA is useful for the evaluation of this variance. Surgeons should be mindful of this variation during operations.

Contusional Cerebellar Hemorrhage Related to Placement in the Protrusion Position After Atlantoaxial Fusion.

BACKGROUND: Various complications after C1 lateral mass and C2 pedicle screw fusion surgery (C1LM-C2PSFS) have been reported. However, to our knowledge, this is the first report of contusional cerebellar hemorrhage caused by placement in the protrusion (chin-out) position after C1LM-2PSFS. CASE DESCRIPTION: An 81-year-old woman complaining of gait disturbance and clumsiness of both hands was diagnosed with cervical myelopathy with atlantoaxial subluxation. After we performed C1LM-C2PSFS, her neurologic deficits gradually improved, and there was no radiologic evidence of construct failure. One month after surgery, she had severe headache and vomiting immediately after taking some medications while in the protrusion position. Head computerized tomography scan showed left cerebellar hemorrhage, and titanium rods penetrated the occipital bone on both sides. Flexion/extension radiography showed no loosening of any screws or rods. However, protrusion radiography showed that the tip of the left titanium rod intruded into the intracranial region. We considered that the penetration of the occipital bone by the left titanium rod caused the contusional left cerebellar hemorrhage. We immediately performed revision surgery to replace the titanium rods on each side with shorter rods, and no cerebrospinal fluid leakage was observed. The headache disappeared after the revision surgery. CONCLUSIONS: We report a case of contusional cerebellar hemorrhage caused by the intrusion of a rod into the occipital bone when the patient was placed in the protrusion position. The rod length on the cranial side must be as short as possible, with careful consideration of placing the head in the protrusion position after C1LM-2PSFS surgery.

Expression of Caspase Signaling Components in the Outer Membranes of Chronic Subdural Hematomas.

Chronic subdural hematoma (CSDH) is fundamentally treatable through surgery, although CSDH recurs in some cases. We have observed several cases of spontaneous resolution of CSDH outer membranes, including in trabecular CSDH, after trepanation surgery. In this study, we examined the expression of molecules involved in caspase signaling in CSDH outer membranes. Eight patients whose outer membranes were obtained successfully during trepanation surgery were included in this study. The expression of Fas; Fas-associated death domain (FADD); tumor necrosis factor receptor type 1-associated death domain (TRADD); receptor-interacting protein (RIP); caspases 3, 7, 8, and 9; poly-(ADP-ribose) polymerase (PARP); DNA fragmentation factor 45 (DFF45) and ß-actin was examined by Western blot analysis. The expression levels of PARP, caspase-3, and cleaved caspase-3 were also examined by immunohistochemistry. Fas; FADD; TRADD; RIP; caspases 3, 7, 8, and 9; PARP, and DFF45 were detected in nearly all samples. Caspase-3 and PARP were localized in the endothelial cells of vessels and in fibroblasts in CSDH outer membranes. In addition, cleaved caspase-3 was detected in fibroblasts. We detected molecules of the caspase signaling pathway in CSDH outer membranes. In particular, cleaved caspase-3 was detected, which suggests that apoptosis may occur within these membranes. Thus, during the growth of CSDH outer membranes, the caspase signaling pathway may be restrained. Once the pathway is activated, gradual resolution of CSDH outer membranes may occur. Therefore, these molecules may be novel therapeutic targets for intractable CSDH.

Inhibitory Mechanism of the Outer Membrane Growth of Chronic Subdural Hematomas.

We previously demonstrated that the inflammatory cytokine interleukin-6 (IL-6) activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway in fibroblasts within the outer membranes of chronic subdural hematomas (CSDHs), and the activation of this pathway may induce CSDH outer membrane growth. The inhibitory system for this signal transduction pathway is unknown. CSDH fluids were obtained from 10 patients during trepanation surgery as the case group, and cerebrospinal fluid (CSF) samples were obtained from seven patients suffering from subarachnoid hemorrhage (SAH) on Day 1 as the control group. The concentrations of IL-6, soluble IL-6 receptor (sIL-6R), and soluble gp130 (sgp130) in CSDH fluid and CSF were measured using enzyme immunoassay kits. The co-localization of IL-6 and sgp130 in CSDH fluid was examined by immunoprecipitation. The expression levels of STAT3, JAK2, suppressor of cytokine signaling 3 (SOCS3), and protein inhibitor of activated Stat3 (PIAS3) in the outer membranes of CSDHs were examined by immunostaining. Soluble IL-6R and sgp130 concentrations in CSDH fluid were significantly higher than those in CSF after SAH. Sgp130 and IL-6 were co-immunoprecipitated from CSDH fluid. Immunostaining revealed STAT3, JAK2, SOCS3, and PIAS3 expression in fibroblasts located in the outer membranes of CSDHs. Soluble gp130 binds to IL-6/sIL-6R and acts as an antagonist of the JAK/STAT signaling pathway. SOCS3 also binds to JAK and inhibits its signaling pathway. In addition, PIAS3 regulates STAT3 activation. These factors might down-regulate the IL-6/JAK/STAT signaling pathway in fibroblasts within CSDH outer membranes. Therefore, these molecules may be novel therapeutic targets for the inhibition of CSDH growth.

Activation of Nuclear Factor-kappa B in Endothelial Cells of Chronic Subdural Hematoma Outer Membranes.

BACKGROUND: Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Nuclear factor-kappa B (NF-κB) induces the production of inflammatory cytokines and adhesion molecules, which play an essential role in angiogenesis and inflammation. Recently, the double-stranded RNA-activated protein kinase (PKR) was shown to directly interact with NF-κB subunits to influence its transcriptional activity. OBJECTIVE: To examine the expression of NF-κB signaling pathway components and PKR in CSDH outer membranes. METHODS: Eight patients whose outer membranes were successfully obtained during trepanation surgery were included in this study. The IκBα, IKKß, IKKγ, NF-κB, phosphorylated ( p )-NF-κB, and PKR expression levels were examined using western blotting analysis. NF-κB expression was also examined using immunohistochemistry. We investigated whether CSDH fluid could activate NF-κB in cultured endothelial cells in Vitro. RESULTS: The IκBα, IKKß, IKKγ, and NF-κB levels were approximately the same. Additionally, p -NF-κB and PKR were detected at similar levels. Immunostaining showed that NF-κB was expressed in the vascular endothelium. p -NF-κB expression in endothelial cells was significantly induced immediately after treatment with CSDH fluid. Furthermore, NF-κB activation was significantly inhibited by treatment with antibodies directed against vascular endothelial growth factor. CONCLUSION: PKR might activate NF-κB through vascular endothelial growth factor in endothelial cells, which might be associated with endothelial cell proliferation in the CSDH outer membrane. Thus, the NF-κB signaling pathway could play a critical role in CSDH growth.