Radiological predictive factors for regrowth of residual benign meningiomas.

The pre- and postoperative radiological predictive factors for the regrowth of residual benign meningiomas were investigated in 80 of 327 patients who underwent first surgery for intracranial meningioma, who met the following conditions: residual tumor observed on postoperative imaging, follow up for more than 5 years or until regrowth of the residual tumor, histological diagnosis of World Health Organization grade I, and no additional therapy performed within 1 month after surgery. These 80 patients were divided into those with no regrowth during the follow-up period (Group A, n = 54) and those with regrowth (Group B, n = 26), and the clinical characteristics and pre- and postoperative imaging findings were compared. Univariate analysis of factors influencing regrowth showed 6 factors were significant: tumor size ≥4 cm (p = 0.043), tumor volume ≥30 cm(3) (p = 0.026), presence of edema (p = 0.036), unclear brain-tumor interface (p < 0.001), presence of a pial-cortical blood supply (p = 0.031), and residual tumor volume ≥3.0 cm(3) (p < 0.001). Multivariate analysis showed only residual tumor volume ≥3.0 cm(3) was significant (p = 0.001). Generally, the significant imaging findings on univariate analysis suggest malignant meningioma. Similar findings may be observed even in grade I cases, and residual tumors may regrow in such cases. The possibility is particularly high if the residual tumor volume exceeds 3.0 cm(3), so early radiotherapy should be performed to prevent regrowth.

Post-operative dexmedetomidine-based sedation after uneventful intracranial surgery for unruptured cerebral aneurysm: comparison with propofol-based sedation.

BACKGROUND: Clinical applications of dexmedetomidine (DEX) for neurosurgical procedures have not been adequately investigated. This study aimed to test the use of DEX infusion, alone or as an adjunct to propofol infusion, as compared to propofol infusion in patients with an unruptured cerebral aneurysm after uneventful intracranial procedures. METHODS: In this retrospective observational study from a single institute, of 184 patients who underwent uneventful intracranial procedures for an unruptured cerebral aneurysm between January 2003 and March 2007, we reviewed 50 managed with DEX-based sedation (DEX alone or as an adjunct to propofol infusion) between April 2005 and March 2007, and 50 managed with propofol-based sedation (propofol alone) between January 2003 and April 2005. With DEX-based sedation, both intubated and extubated patients received DEX infusion at an initial dose of 0.4 µg/kg/h, followed by a maintenance dose of 0.2-0.7 µg/kg/h. Propofol was used in both groups at a dose range of 0.5-5.0 mg/kg/h. Hemodynamic variables, including heart rate (HR) and blood pressure (BP), and adverse events were recorded and compared between the groups. RESULTS: HR during sedation and systolic BP at 2 h after beginning sedation were significantly lower in the DEX group. No serious adverse events were observed. In the DEX group, 66% were sedated in combination with propofol, of whom 94% were intubated. CONCLUSIONS: DEX could be used safely for both intubated and extubated patients following uneventful intracranial procedures for an unruptured cerebral aneurysm, though it significantly reduced HR. Our findings also indicate that it is preferable to add low-dose propofol to DEX for management of intubated patients.

[Symptomatic radiation necrosis 10 years after gamma knife surgery for arteriovenous malformations: a case report].

We present a case of symptomatic radiation necrosis after gamma knife surgery for arteriovenous malformations (AVMs). Initially, at the age of 30 years the patient was treated with gamma knife surgery. Angiography performed 2 years after radiation therapy revealed that the AVMs were completely obliterated. Five years later, the patient had a generalized convulsion and a computed tomography (CT) scan showed a cystic formation in the irradiated area. The patient was treated with a cyst-peritoneal (CP) shunt. Thereafter, the patient seemed to be cured, but 5 years after CP shunt treatment, the patient had right hemiparesis, agraphia, and right hemianopsia. Magnetic resonance imaging (MRI) revealed radiation necrosis in the left parietooccipital region and midline shift of the brain. The patient was operated on and the hyalinized nidus and CP shunt tube were removed. The patient fully recovered from the symptoms and resumed work.

DNA ligase IV is a potential molecular target in ACNU sensitivity.

Nimustine (ACNU) is a chloroethylating agent which was the most active chemotherapy agent used for patients with high-grade gliomas until the introduction of temozolomide, which became the standard of care for patients with newly diagnosed glioblastomas in Japan. Since temozolomide was established as the standard first-line therapy for glioblastoma multiforme (GBM), ACNU has been employed as a salvage chemotherapy agent for recurrent GBM in combination with other drugs. The acting molecular mechanism in ACNU has yet to be elucidated. ACNU is a cross-linking agent which induces DNA double-strand breaks (DSBs). The work described here was intended to clarify details in repair pathways which are active in the repair of DNA DSBs induced by ACNU. DSBs are repaired through the homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways. Cultured mouse embryonic fibroblasts were used which have deficiencies in DNA DSB repair genes which are involved in HR repair (X-ray repair cross-complementing group 2 [XRCC2] and radiation sensitive mutant 54 [Rad54]), and in NHEJ repair (DNA ligase IV [Lig4]). Cellular sensitivity to ACNU treatment was evaluated with colony forming assays. The most effective molecular target which correlated with ACNU cell sensitivity was Lig4. In addition, it was found that Lig4 small-interference RNA (siRNA) efficiently enhanced cell lethality which was induced by ACNU in human glioblastoma A172 cells. These findings suggest that the down-regulation of Lig4 might provide a useful tool which can be used to increase cell sensitivity in response to ACNU chemotherapy.

Orbital schwannoma extending to the lateral wall of the cavernous sinus through the superior orbital fissure--case report.

A 58-year-old man presented with a rare orbitocavernous sinus schwannoma that originated from the orbital opthalmic nerve, and manifested as slowly progressive hypesthesia of the right side of the forehead, proptosis, and ocular pain with rapidly worsening visual acuity. Magnetic resonance imaging revealed a huge orbital tumor extending to the lateral wall of the cavernous sinus through the superior orbital fissure. Microsurgical total resection of the tumor was achieved using an epidural orbitofrontal approach with orbito-fronto-zygomatic craniotomy. The histological diagnosis was schwannoma with Antoni type A formation. The postoperative course was uneventful except for the hypesthesia on the right side of the forehead and transient oculomotor paralysis. Surgery was effective to relieve the symptoms and improve the activities of daily living.

Evaluation of posttetanic motor evoked potentials--the influences of repetitive use, the residual effects of tetanic stimulation to peripheral nerve, and the variability.

BACKGROUND: Recently, we developed a new technique to augment myogenic motor evoked potentials (MEPs), called as posttetanic MEPs (p-MEPs), in which tetanic stimulation is applied to peripheral nerve before transcranial stimulation. However, the data on p-MEPs are limited. This study was conducted; (1) to evaluate the influences of repetitive use of p-MEPs on p-MEP amplitudes, (2) to evaluate the residual effects of use of p-MEPs on subsequent conventional MEPs (c-MEPs), and (3) to compare the variability of p-MEPs with that of c-MEPs. METHODS: Sixty patients under propofol/fentanyl anesthesia with partial neuromuscular blockade were enrolled. For p-MEP measurements, tetanic stimulation was applied to posterior tibial nerve 1 second before transcranial stimulation. In study 1, p-MEPs were repetitively recorded with intervals of 10 or 60 seconds. In study 2, the amplitudes of c-MEPs recorded 15, 30, 60, and 120 seconds after p-MEP recordings were compared with those of control. In study 3, the coefficients of variation of c-MEP and p-MEP responses were compared. RESULTS: The repetitive use of p-MEP with an interval of 10 seconds, but not 60 seconds, induced a significant reduction of p-MEP amplitude. Amplitudes of c-MEP were significantly increased when applied within 60 seconds after p-MEP recordings. The coefficient of variations of p-MEPs was similar to those of c-MEPs. CONCLUSIONS: The results indicated that the amplitudes of p-MEP and c-MEP might be affected when applied with a short interval after p-MEP recording.

Artery-to-artery embolism with a mobile mural thrombus due to rotational vertebral artery occlusion.

Rotational vertebral artery (VA) occlusion can cause ischemic strokes due to hemodynamic insufficiency and possibly artery-to-artery (A-to-A) embolism. The former is known as bow hunter's stroke. The latter has been proposed only from indirect evidence. We have described a 7-year-old boy with cerebral infarction associated with A-to-A embolism due to repetitive rotational VA occlusion. He had a mobile mural thrombus at the VA occlusion site on head rotation. Surgical treatment may effectively prevent recurrences.

DNA ligase IV as a new molecular target for temozolomide.

Temozolomide (TMZ) is a methylating agent used in chemotherapy against glioblastoma. This work was designed to clarify details in repair pathways acting to remove DNA double-strand breaks (DSBs) induced by TMZ. Cultured mouse embryonic fibroblasts were used which were deficient in DSB repair genes such as homologous recombination repair-related genes X-ray repair cross-complementing group 2 (XRCC2)and radiation sensitive mutant54 (Rad54), non-homologous end joining repair-related gene DNAligase IV (Lig4). Cell sensitivity to drug treatments was assessed using colony forming assays. The most effective molecular target which was correlated with TMZ cell sensitivity was Lig4. In addition, it was found that small interference RNAs (siRNA) for Lig4 efficiently enhanced cell lethality induced by TMZ in human glioblastoma A172 cells. These findings suggest that down regulation of Lig4 might provide a useful tool for cell sensitization during TMZ chemotherapy.

Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells: necessity of immunosuppressive treatment for sustained improvement.

OBJECTIVE: The purpose of the present study was to examine the efficacy of transplantation of mouse embryonic stem (ES) into Parkinson's disease (PD) model mice as well as the necessity of immunosuppression in allogeneic donor-host combinations. MATERIALS AND METHODS: ES cells, derived from SvJ129 strain mice, were differentiated into tyrosine hydroxylase (TH)-positive neurons in vitro by an embryoid body (EB)-based multistep differentiation method and used as graft cells for PD mice, which were prepared by injection of 6-hydroxydopamine (OHDA) into C57BL/6, BALB/c and C3H/HeN strains. Mice from each strain were divided into Groups 1-3. Four weeks after the 6-OHDA injection, Group 1 received phosphate-buffered saline in the striatum wounds, while Group 2 received 2 x 10(4) graft cells, and Group 3 mice received 2 x 10(4) graft cells and were also treated with cyclosporine A. RESULTS: Apomorphine-induced rotational behavior was improved in Groups 2 and 3, but not in Group 1. However, the behavioral improvement ceased later in Group 2, whereas sustained improvement was observed in Group 3 throughout the 8 week observation period after transplantation. ES-derived TH(+) cells were found at the grafted sites at the end of the experiment in Groups 2 and 3, and tended to be more abundant in Group 3. CONCLUSION: Intra-striatum transplantation of ES-derived dopaminergic neurons was effective in treating PD mice, even in allogeneic donor-host combinations. Immunosuppressive treatment did not have an effect on initial behavioral restoration after transplantation; however, it was necessary for sustained improvement over a prolonged period.

Cotransplantation of mouse embryonic stem cells and bone marrow stromal cells following spinal cord injury suppresses tumor development.

Embryonic stem (ES) cells are a potential source for treatment of spinal cord injury (SCI). Although one of the main problems of ES cell-based cell therapy is tumor formation, there is no ideal method to suppress tumor development. In this study, we examined whether transplantation with bone marrow stromal cells (BMSCs) prevented tumor formation in SCI model mice that received ES cell-derived grafts containing both undifferentiated ES cells and neural stem cells. Embryoid bodies (EBs) formed in 4-day hanging drop cultures were treated with retinoic acid (RA) at a low concentration of 5 x 10(-9) M for 4 days, in order to allow some of the ES cells to remain in an undifferentiated state. RA-treated EBs were enzymatically digested into single cells and used as ES cell-derived graft cells. Mice transplanted with ES cell-derived graft cells alone developed tumors at the grafted site and behavioral improvement ceased after day 21. In contrast, no tumor development was observed in mice cotransplanted with BMSCs, which also showed sustained behavioral improvement. In vitro results demonstrated the disappearance of SSEA-1 expression in cytochemical examinations, as well as attenuated mRNA expressions of the undifferentiated markers Oct3/4, Utf1, Nanog, Sox2, and ERas by RT-PCR in RA-treated EBs cocultured with BMSCs. In addition, MAP2-immunopositive cells appeared in the EBs cocultured with BMSCs. Furthermore, the synthesis of NGF, GDNF, and BDNF was confirmed in cultured BMSCs, while immunohistochemical examinations demonstrated the survival of BMSCs and their maintained ability of neurotrophic factor production at the grafted site for up to 5 weeks after transplantation. These results suggest that BMSCs induce undifferentiated ES cells to differentiate into a neuronal lineage by neurotrophic factor production, resulting in suppression of tumor formation. Cotransplantation of BMSCs with ES cell-derived graft cells may be useful for preventing the development of ES cell-derived tumors.

[Case report of intrathecal baclofen administration in a child with severe spasticity attributable to traumatic brain injury].

We report a pediatric case of intrathecal baclofen therapy for severe spasticity following traumatic brain injury. A 14-year-old boy suffered from traumatic brain injury by traffic accident in 2005. Subsequently, he experienced tetraparesis and severe spasticity with spontaneous spasms. He underwent baclofen screening test, and his spasticity was improved. Thereafter intrathecal baclofen therapy was performed. Following baclofen pump implantation, Ashworth Score decreased from 4.0 points to 3.0 in lower limbs, and from 3.0 to 1.5 in upper limbs. His muscle tone was reduced and occurrence of spontaneous spasms stopped. Intrathecal baclofen therapy was observed to be an effective treatment for severe spasticity in childhood. Since children receiving the therapy demonstrated longer survival period than adults, long-term follow-up of this therapy is warranted.

"Sukeroku sign" and "dent internal-capsule sign"--identification guide for targeting the subthalamic nucleus for placement of deep brain stimulation electrodes.

INTRODUCTION: The purpose of this study was to assess the usefulness of signs ("Sukeroku sign" and "dent internal-capsule sign") for the recognition of subthalamic nucleus (STN). MATERIALS AND METHODS: Five Parkinson's disease cases in which there was a successful placement of deep brain stimulation (DBS) electrodes at the STN were retrospectively reviewed. Five radiologists who were not engaged in localization of STNs in clinical practice were asked to locate the STNs before and after instructions on the signs. We evaluated the deviation between the reader-located points and the location of the DBS electrode for which there had been a successful installation. RESULTS: After instruction, there was a significant reduction in the deviation between the reader-located points and the DBS electrode. The time required for localization was also reduced after the instructions. CONCLUSION: Sukeroku sign and dent internal-capsule sign are feasible indicators of STN and seem to be useful in helping to identify the STN.

Cotransplantation of Mouse Embryonic Stem Cells and Bone Marrow Stromal Cells following Spinal Cord Injury Suppresses Tumor Development.

Embryonic stem (ES) cells are a potential source for treatment of spinal cord injury (SCI). Although one of the main problems of ES cell-based cell therapy is tumor formation, there is no ideal method to suppress tumor development. In this study, we examined whether transplantation with bone marrow stromal cells (BMSCs) prevented tumor formation in SCI model mice that received ES cell-derived grafts containing both undifferentiated ES cells and neural stem cells. Embryoid bodies (EBs) formed in 4-day hanging drop cultures were treated with retinoic acid (RA) at a low concentration of 5 × 10-9 M for 4 days, in order to allow some of the ES cells to remain in an undifferentiated state. RA-treated EBs were enzymatically digested into single cells and used as ES cell-derived graft cells. Mice transplanted with ES cell-derived graft cells alone developed tumors at the grafted site and behavioral improvement ceased after day 21. In contrast, no tumor development was observed in mice cotransplanted with BMSCs, which also showed sustained behavioral improvement. In vitro results demonstrated the disappearance of SSEA-1 expression in cytochemical examinations, as well as attenuated mRNA expressions of the undifferentiated markers Oct3/4, Utf1, Nanog, Sox2, and ERas by RT-PCR in RA-treated EBs cocultured with BMSCs. In addition, MAP2-immunopositive cells appeared in the EBs cocultured with BMSCs. Furthermore, the synthesis of NGF, GDNF, and BDNF was confirmed in cultured BMSCs, while immunohistochemical examinations demonstrated the survival of BMSCs and their maintained ability of neurotrophic factor production at the grafted site for up to 5 weeks after transplantation. These results suggest that BMSCs induce undifferentiated ES cells to differentiate into a neuronal lineage by neurotrophic factor production, resulting in suppression of tumor formation. Cotransplantation of BMSCs with ES cell-derived graft cells may be useful for preventing the development of ES cell-derived tumors.

Carpal tunnel syndrome: electrophysiological grading and surgical results by minimum incision open carpal tunnel release.

The safety and effectiveness of the minimum incision technique were assessed in 138 hands of 108 consecutive patients with carpal tunnel syndrome treated from April 1, 1997 to March 31, 2006. Clinical and electrophysiological examinations were conducted before and after surgical decompression. All hands were divided into early, mild, moderate, and severe groups based on preoperative electrophysiological severity. We examined the surgical outcomes of the affected hands in each group. Nocturnal or daytime dysesthesia, which had been present in 132 (96%) of the 138 hands preoperatively, was completely relieved in 124 (94%) of the 132 hands. Complete relief was achieved in 7 (100%) of the 7 hands in the early group, 68 (99%) of the 69 hands in the mild group, and 45 (94%) of the 48 hands in the moderate group. Complete relief was achieved only in 4 (50%) of the 8 hands in the severe group, and 3 (38%) of the 8 hands did not show any improvement. No painful or hypertrophic scar formation was observed in this series. Only 2 patients complained of postoperative scar discomfort after more than 12 months, which completely disappeared by 14 months after surgery. Minimum incision open carpal tunnel release is a safe and reliable procedure with a high rate of functional improvement and patient satisfaction. Postoperative results were satisfactory regardless of the degree of preoperative electrophysiological severity if preoperative sensory nerve action potentials were detected.

CoCl(2) inhibits neural differentiation of retinoic acid-treated embryoid bodies.

The effects of CoCl(2) on retinoic acid (RA)-treated embryoid bodies (EBs) were investigated. Four-day EBs were treated with 5x10(-6) M of RA for 4 d, then subjected to attached culturing for 7 d in the presence of CoCl(2) at 0, 20, and 100 microM. Differentiation into MAP2- and GFAP-immunopositive cells was inhibited by CoCl(2) in a dose-dependent manner. Next, RA-treated EBs were dissociated into single cells and cultured for 7 d at an initial cell density of 1x10(3)/cm(2). The number of cells increased in a CoCl(2)-dose dependent fashion. In cultures with 100 microM of CoCl(2), more than 90% of the cells were immunopositive for nestin and nestin-immunopositive cells formed clusters, while there were few cells immunopositive for MAP2 or GFAP. These results suggest that CoCl(2) inhibits neural differentiation of RA-treated EB cells and promotes the proliferation of nestin-immunopositive cells, i.e., embryonic stem (ES)-derived neural stem-like cells.

[Surgical treatment of intrarcranial dural arteriovenous fistulas].

Surgical treatment is indicated in patients who present clinical symptoms for intracranial dural arteriovenous fistula and retrograde cortical venous filling on cerebral angiography. Further, surgery is indicated in those patients that cannot be cured by endovascular procedures. For dural arteriovenous fistulas in the anterior fossa, tentorium, craniovertebral junction or convex, surgery was considered as the first option. Morphologically, non-sinus dural arteriovenous fistulas and dural arteriovenous fistulas with isolated sinus should be treated with surgery. The surgical procedure for intracranial dural arteriovenous fistulas basically consisted of the coagulation and disconnection of the retrograde-flow cortical veins at the point of entry into the dural sinus, and the coagulation of the affected dura and dural sinus. The remaining affected dural sinus could be removed if the patient could tolerate the surgery. Preoperative transarterial embolization of the feeding artery is effective in reducing the amount of blood loss intraoperatively. During surgery, microvascular Doppler sonography is useful for confirming the retrograde-flow cortical veins, and stereotactic localization system and duplicated ultrasound sonography are also useful in detecting the shunting point of the dural arteriovenous fistula and the range of the affected dura and dural sinus. The surgical procedure for intracranial dural arteriovenous fistulas is a radical and invasive treatment. However, surgery is a reliable treatment because it can cure the intracranial dural arteriovenous fistula and correct the intracranial hemodynamics immediately after surgery due to the extirpation of the dural arteriovenous shunt and retrograde-flow cortical veins.

Protective effect of C1 esterase inhibitor on acute traumatic spinal cord injury in the rat.

OBJECTIVE: The complement system and activated neutrophils are thought to play a major role in initiating some of the inflammatory events that occur in spinal cord injury. The aim of the present study was to assess the effects of C1 esterase inhibitor (C1-INH) on traumatic spinal cord injury (SCI) in the rat. METHODS: Thirty-eight male Wistar rats were used. Just after SCI by a pneumatic impact device, C1-INH (n=16, C1-INH group) or saline (n=16, saline group) was administered. Sham operated animals (n=6, sham group) received only laminectomy. Eighteen (six from each group) rats were killed and an assessment of leukocyte infiltration by myeloperoxidase (MPO) activity and immunoreactivity of MPO were performed 24 hours after SCI. Twenty (ten from each of C1-INH and saline groups) rats were examined using behavioral function on post-operative days. They were also examined after 7 days by histologic analysis using Luxol fast blue for axons and myelin. Lesion volume was calculated by considering a lesion as being composed of two cones with juxtaposed bases. During the experiment, sequential changes in regional spinal cord blood flow (rSCBF) were measured using the laser Doppler (LD) scanning technique. RESULTS: The recovery of motor function was better in the C1-INH group than in the saline group. In the C1-INH group, immunoreactivity of MPO showed a tendency to be smaller than that of the saline group. Lesion volume was significantly smaller in the C1-INH group than in the control group (p<0.01) and MPO activity was also significantly smaller in the C1-INH group than in the control group (p<0.01). After SCI, the rSCBF value decreased gradually and significantly in both injured groups. Significant differences were observed from 30 to 120 minutes after SCI (p<0.05). DISCUSSION: The results of this study provided the first evidence that C1-INH reduced accumulation of polymorphonuclear leukocytes (PMLs) and neuronal damage in acute stage after SCI. This protection was not related to an improvement in rSCBF.

The effects of the neuromuscular blockade levels on amplitudes of posttetanic motor-evoked potentials and movement in response to transcranial stimulation in patients receiving propofol and fentanyl anesthesia.

BACKGROUND: Patient movement in response to transcranial stimulation during monitoring of myogenic motor-evoked potentials (MEPs) may interfere with surgery. We recently reported a new technique to augment the amplitudes of myogenic MEPs, called "post-tetanic MEPs (p-MEPs)," in which tetanic stimulation of a peripheral nerve was applied prior to transcranial stimulation. We conducted the present study to determine an appropriate level of neuromuscular blockade during the monitoring of p-MEPs with a focus on patient movement. METHODS: In 15 patients under propofol/fentanyl anesthesia, conventional MEPs (c-MEPs) and p-MEPs in response to transcranial electrical stimulation were recorded from the abductor hallucis muscle. For p-MEP recording, tetanic stimulation to the posterior tibial nerve at an intensity of 50 mA for 5 s was started 6 s prior to transcranial stimulation. The level of neuromuscular blockade was assessed by recording the amplitude of compound muscle action potentials (T1) from the abductor hallucis brevis muscle in response to supramaximal electrical stimulation of the median nerve at the wrist. After the baseline recordings of c-MEP and p-MEP at a T1 of 50% of control, 0.1 mg/kg of vecuronium was injected and the amplitudes of c-MEPs and p-MEPs were recorded. Patient movement was also assessed with the movement score ranging from 1 to 4 (1 = no movement, 4 = severe movement). RESULTS: T1, %T1, the amplitudes of c-MEPs and p-MEPs, and the movement score changed in parallel after the administration of vecuronium. The amplitudes of p-MEPs before and 15-45 min after the administration of vecuronium were significantly higher than those of c-MEPs. When T1 and %T1 were less than and equal to 1 mV and 10%, respectively, the movement score was 1 or 2 in all patients, indicating that microscopic surgery was possible without the interruption of surgical procedures. When T1 was around 1 mV (0.8-1.2 mV), the success rates of recording of c-MEPs and p-MEPs were 73% (11 of 15) and 100% (15 of 15), respectively. CONCLUSIONS: Under propofol/fentanyl anesthesia, p-MEP could be recorded at a T1 of 1 mV, in which patient movement in response to transcranial stimulation did not interfere with surgery. This technique may be used in patients without preoperative motor deficits, in which patient movement during surgical procedures is not preferable.

Expression of angiogenic growth factor in the rat DAVF model.

OBJECTIVE: The precise mechanisms responsible for the development and growth of dural arteriovenous fistula (DAVF) remain unclear, but it has been hypothesized that vascular endothelial growth factor (VEGF) might be involved in the pathogenesis. The aim of this study was to examine the expression of VEGF in the rat DAVF model. METHODS: Forty-five Sprague-Dawley rats were used in two experiments. In Experiment 1 (n = 20, including sham-operated controls), VEGF expression was analysed by Western blots in three different rat DAVF models: model I: common carotid artery-external jugular vein (CCA-EJV) anastomosis (n = 5); model II: sagittal sinus thrombosis and bipolar coagulation of the vein draining the transverse sinus (n = 5); model III: CCA-EJV anastomosis and bipolar coagulation of the vein draining the transverse sinus and sagittal sinus thrombosis to induce venous hypertension (n = 5). Based on the results of Experiment 1, Western blots were performed at weekly intervals 1, 2 and 3 weeks in Experiment 2 following induction of venous hypertension in model III (n = 5 at each time point and n = 5 sham controls); in addition, VEGF expression was immunohistochemically examined in the dura and the brain near the occluded sinus in five model III animals after 1 week. RESULTS: In Experiment 1, Western blot analysis showed barely detectable bands with molecular weights of 45 kD, corresponding to VEGF, in the sham group, but the highest level of VEGF was induced in model III, followed by models I and II (model III>model I>model II). In Experiment 2, the expression of VEGF peaked 1 week after induction of venous hypertension in model III, decreasing in a linear fashion over 2 and 3 weeks (week 1>weeks 2 and 3). The expression of immunoreactive VEGF was restricted in the connective tissue and the endothelial layer of the dura matter, cerebral cortical tissue and neurons of the basal ganglia. CONCLUSION: Our results strongly suggest a possible contribution of an angiogenic factor to the growth of DAVF. Venous ischemia by venous hypertension might be a mechanism for inducing up-regulation of angiogenic factor expression.