Borax induces ferroptosis of glioblastoma by targeting HSPA5/NRF2/GPx4/GSH pathways.

Glioblastoma multiforme (GBM) is a highly aggressive and lethal form of primary brain tumour. Borax has been demonstrated to exhibit anti-cancer activity through cell death pathways. However, the specific impact of borax on ferroptosis in GBM is not well-established, and the underlying regulatory mechanisms remain unclear. Initially, the effective concentration of borax on cell viability and proliferation in U251 and A172 cells was determined. Subsequently, the effects of borax on the wound healing were analysed. Nuclear factor erythroid 2-related factor 2 (NRF2), glutathione peroxidase 4 (GPx4), glutathione (GSH), HSP70 protein 5 (HSPA5), malondialdehyde (MDA) levels and caspase-3/7 activity were determined in borax-treated and untreated cells. Finally, the protein expression levels of HSPA5, NRF2 and GPx4 were analysed. Borax suppressed cell viability and proliferation in U251 and A172 cells in a concentration- and time-dependent manner. In addition, borax treatment decreased GPx4, GSH, HSPA5 and NRF2 levels in U251 and A172 cells while increasing MDA levels and caspase-3/7 activity. Moreover, borax reduced mRNA and protein levels of HSPA5, NRF2 and GPx4 in U251 and A172 cells. Consequently, borax may induce ferroptosis in GBM cells and regulate the associated regulatory mechanisms targeting NRF2 and HSPA5 pathways. This knowledge may contribute to the development of novel therapeutic approaches targeting ferroptosis in GBM and potentially improve patient outcomes.

Borax regulates iron chaperone- and autophagy-mediated ferroptosis pathway in glioblastoma cells.

Glioblastoma (GBM) is classified as a stage-IV glioma. Unfortunately, there are currently no curative treatments for GBM. Poly(rC)-binding protein 1 (PCBP1) is a cytosolic iron chaperone with diverse functions. PCBP1 is also known to regulate autophagy, but the role of PCBP1 in ferroptosis, iron-dependent cell death pathway, remains unrevealed in GBM cells. Here, we investigated the effects of borax, a boron compound, on the ferroptosis signaling pathway mediated by PCBP1 and autophagy. The study analyzed cell viability, proliferation, and cell cycle on U87-MG and HMC3 cells to investigate the effects of borax. After determining the cytotoxic concentrations of borax, morphological analyzes and measurement of PCBP1, Beclin1, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPx4) and acyl-CoA synthetase long chain family member 4 (ACSL4) levels were performed. Finally, expression levels of PCBP1, Beclin1, GPx4 and ACSL4, and caspase-3/7 activity were determined. We found that borax reduced U87-MG cell viability in a concentration- and time-dependent manner. Additionally, borax altered cell proliferation and remarkably reduced S phase in the U87-MG cells and exhibited selectivity by having an opposite effect on normal cells (HMC3). According to DAPI staining, borax caused nuclear deficits in U87-MG cells. The result showed that borax in U87-MG cells induced reduction of the PCBP1, GSH, and GPx4 and enhancement of Beclin1, MDA, and ACSL4. Furthermore, borax triggered apoptosis by activating caspase 3/7 in U87-MG cells. Our study indicated that the borax has potential as an anticancer treatment for GBM via regulating PCBP1/Beclin1/GPx4/ACSL4 signaling pathways.

Successful endoscopic third ventriculostomy in children depends on age and etiology of hydrocephalus: outcome analysis in 51 pediatric patients.

PURPOSE: Endoscopic third ventriculostomy (ETV) has become the method of choice in the treatment of hydrocephalus. Age and etiology could determine success rates (SR) of ETV. The purpose of this study is to assess these factors in pediatric population. METHODS: Retrospective study on 51 children with obstructive hydrocephalus that underwent ETV was performed. The patients were divided into three groups per their age at the time of the treatment: < 6, 6-24, and > 24 months of age. All ETV procedures were performed by the same neurosurgeon. RESULTS: Overall SR of ETV was 80% (40/51) for all etiologies and ages. In patients < 6 months of age SR was 56.2% (9/16), while 6-24 months of age was 88.9% (16/18) and > 24 months was 94.1% (16/17) (p = 0.012). The highest SR was obtained on aqueductal stenosis. SR of posthemorrhagic, postinfectious, and spina bifida related hydrocephalus was 60% (3/5), 50% (1/2), and 14.3% (1/7), respectively. While SR rate at the first ETV attempt was 85.3%, it was 76.9% in patients with V-P shunt performed previously (p = 0.000). CONCLUSIONS: Factors indicating a potential failure of ETV were young age and etiology such as spina bifida, other than isolated aqueductal stenosis. ETV is the method of choice even in patients with former shunting. Fast healing, distensible skulls, and lower pressure gradient in younger children, all can play a role in ETV failure. Based on our experience, ETV could be the first method of choice for hydrocephalus even in children younger than 6 months of age.

Radiologic and histopathologic effects of favipiravir and hydroxychloroquine on fracture healing in rats.

Fracture healing is a process in which many factors interact. In addition to many treatments, physical and biological therapy methods that affect different steps of this process, there are many biological and chemical agents that cause fracture union delay. Although the number of studies on fracture healing is increasing day by day, the mechanism of fracture healing, which is not fully understood, still attracts the attention of all researchers. In this study, we aimed to investigate the effects of favipiravir and hydroxychloroquine used in the treatment of COVID-19. In this study, 48 male Wistar rats weighing 300 ± 50 g were used. Each group was divided into eight subgroups of six rats each to be sacrificed at the 2nd and 4th weeks and evaluated radiologically and histologically. Favipiravir (group 1), hydroxychloroquine (group 2), favipiravir + hydroxychloroquine (group 3), and random control (group 4) were used. A statistically significant difference was observed between the 15th day histological scoring averages of the groups (p < 0.05). Although there was no statistically significant difference between the 15th day radiological score distributions of the groups (p > 0.05), we obtained different results in terms of complete bone union distributions and radiological images of the fracture line. Although favipiravir has a negative effect on fracture union in the early period, favipiravir may have a positive effect on fracture union in the late period. We did not find any effect of hydroxychloroquine on fracture union.

Boric acid Increases Susceptibility to Chemotherapy by Targeting the Ferritinophagy Signaling Pathway in TMZ Resistant Glioblastoma Cells.

Glioblastoma (GBM) is a common and highly lethal form of brain cancer. Temozolomide (TMZ) is the primary chemotherapy used for GBM, but it has limited effectiveness, with about half of the patients developing resistance. Iron regulatory proteins (IRPs) modulate genes involved in iron metabolism, while the nuclear receptor coactivator 4 (NCOA4) controls iron metabolism through a process called ferritinophagy. In this study, we investigated whether boric acid increases chemosensitivity mediated by ferritinophagy via the NCOA4 and IRP2 signaling pathways in TMZ-resistant GBM cells. First, we generated TMZ-resistant GBM cells (A172-R and T98G-R cells). Next, we investigated the effects of boric acid on cell viability, proliferation, cell cycle, and cell morphology in these cells. Additionally, following boric acid treatment, we analyzed the expression and protein levels of various biochemical markers in these cells. Boric acid treatment in A172-R and T98G-R cells suppressed cell viability and proliferation, arrested these cells in the G1/G0 cell cycle, and induced morphological differences. Boric acid increased NCOA4, IRP2, iron, and malondialdehyde (MDA) levels in A172-R and T98G-R cells, while glutathione (GSH) and glutathione peroxidase 4 (GPx4) levels decreased. Moreover, boric acid treatment increased intracellular iron levels and lipid peroxidation by inducing NCOA4 and IRP2 expression levels in TMZ-resistant cells. According to our results, boric acid may regulate chemosensitivity in A172-R and T98G-R cells mediated by NCOA4 and IRP2. In conclusion, the manipulative effects of boric acid on the ferritinophagy pathway hold the potential to sensitize TMZ-resistant GBM cells to chemotherapy.

Blocking VEGF by Bevacizumab Attenuates VEGF-Induced Vasospasm After Experimental Subarachnoid Hemorrhage in Rabbits.

OBJECTIVE: Vasospasm after subarachnoid hemorrhage (SAH) plays a vital role in the development of delayed cerebral ischemia. Anti- vascular endothelial growth factor (VEGF) antibodies, like bevacizumab (BEV), may attenuate VEGF-stimulated angiogenesis, reduced vascular cell proliferation, and improve vasospasm after SAH. METHODS: Thirty-two adult male New Zealand white rabbits were randomly divided into 4 groups of 8 rabbits in each group: group 1 (control); group 2 (SAH); group 3 (SAH + vehicle); and group 4 (SAH + BEV). BEV (5 mg/kg, intraperitoneally) was administered 5 minutes after the intracisternal blood injection and continued for 72 hours once per day in the same dose for group 4. Animals were sacrificed 72 hours after SAH. Basilar artery cross-sectional areas, arterial wall thicknesses, and hippocampal degeneration scores were evaluated in all groups. RESULTS: VEGF is associated with the narrowing of the basilar artery. Treatment with BEV statistically significantly increased the cross-sectional area of the basilar artery when compared with the SAH and the vehicle groups. Basilar artery wall thicknesses in the BEV group was statistically significant smaller than in the SAH and vehicle groups. The hippocampal degeneration scores for the BEV and control groups were similar and significantly lower than those for the SAH and vehicle groups. CONCLUSIONS: Cellular proliferation and subsequent vessel wall thickening is a reason to delay cerebral ischemia and deterioration of the neurocognitive function. Intraperitoneal administration of BEV was found to attenuate cerebral vasospasm and prevent delayed cerebral ischemia and improve neurocognitive function after SAH in rabbits.

Multiple intracranial hydatid cysts in a boy.

Multiple hydatid cysts of the brain are uncommon and may be either primary or secondary. A 15-year-old boy with a huge mass of intracranial hydatid cysts (95x85x80 mm) is presented. The first manifestation was headache and vomiting, which was followed by symptoms of raised intracranial pressure. The patient underwent an urgent operation due to rapidly deteriorating neurological status, and 19 hydatid cysts were removed. Unfortunately, the patient's neurological status did not improve and he died. Hydatid cyst is a benign lesion. Surgery is the standard and most effective treatment for intracranial hydatid cysts. Appropriate and timely management is mandatory for reducing the mortality and morbidity.

Is IL-8 level an indicator of clinical and radiological status of traumatic brain injury?

BACKGROUND: Since understanding the fact that traumatic brain injury includes an inflammatory process, the number of studies of cytokines has increased. The objective of this study was to analyze and discuss the association of interleukin (IL)-8 level with the clinical and radiological status of patients with head trauma. METHODS: Patients who were admitted to our hospital due to head trauma were included in the study. Findings of clinical and laboratory examinations were analyzed. Data regarding patient age, gender, available clinical findings, Glasgow Coma Scale (GCS) score, trauma cause, brain tomography findings, and biochemical laboratory test results were recorded. The patients were divided into 3 groups according to their GCS score: Group I: GCS ≥13, Group II: GCS = 9-12, and Group III: GCS = 3-8. RESULTS: A total of 23 (76.7%) patients were male and 7 (23.3%) were female. Overall, 17 (56.7%) patients were admitted due to a fall, 8 (26.7%) due to a traffic accident, and 5 (16.7%) due to assault. Each group comprised 10 patients. As the GCS score increased, the IL-8 level decreased. The mean IL-8 level was 1.2 pg/mL in Group I, 6.6 pg/mL in Group II, and 4.7 pg/mL in Group III; however, there was no statistically significant difference between the groups (p=0.147). Moreover, the IL-8 level was significantly greater in patients who demonstrated an abnormal tomography finding (p=0.023). CONCLUSION: IL-8 may be a beneficial indicator for monitoring the clinical and radiological status of traumatic brain injury. Nonetheless, studies of larger cohorts in which IL-8 levels are measured at all stages of brain injury and follow-up of long-term prognosis are warranted.

The Preventative Effect of α-Tocopherol on Spinal Epidural Fibrosis After Laminectomy in a Rat Model.

AIM: To assess the efficacy of α-tocopherol as a topical antifibrotic agent on epidural fibrosis in lumbar laminectomy procedures. MATERIAL AND METHODS: A total of 32 adult rats were assigned into four groups, with eight rats in each group. Standard laminectomy was performed in every rat. In group 1, no treatment was administered after laminectomy. In group 2, a saline-soaked absorbable gelatin sponge was left on the dura mater after laminectomy. In group 3, only α-tocopherol was used on the dura mater after laminectomy. In group 4, a gelatin sponge soaked with α-tocopherol was used after laminectomy. En bloc vertebral columns between T10 and L5 were removed after sacrifice on postoperative day 30. Specimens were evaluated for degree of fibrosis and arachnoidal invasions. RESULTS: Statistically significant differences were found in the mean of fibrosis grades between groups (p=0.001). Differences in mean arachnoidal invasion were not statistically significant (p > 0.05). CONCLUSION: Topical application of α-tocopherol could effectively reduce the development of epidural fibrosis in an experimental laminectomy model.

Effect of topical rifamycin application on epidural fibrosis in rats.

OBJECTIVES: This study aims to investigate the effects of topical rifamycin SV application on epidural fibrosis formation in a rat model. MATERIALS AND METHODS: Between March 2015 and April 2015, a total of 20 Wistar rats were equally and randomly divided into laminectomy only group (control group) and laminectomy and rifamycin SV group (treatment group). Laminectomy was performed between L3-L5 in all rats. Surgical field was irrigated with 1 mL rifamycin SV (1 mL). After four weeks, vertebral columns of the rats were removed en bloc between the L1 and L5 levels, and epidural fibrosis and arachnoid involvement were histopathologically evaluated and graded. RESULTS: Grade 3 epidural fibrosis formation ratio was lower in the treatment group (40%) compared to the control group (80%). However, there was no statistically significant difference between the treatment and control groups in terms of epidural fibrosis (p=0.164) and arachnoid involvement (p=0.303). CONCLUSION: Intraoperative rifamycin irrigation tends to reduce epidural fibrosis formation risk, although not statistically significant.

Investigation of Lateral Epicondylitis in Neurosurgeons.

AIM: To investigate the frequency of lateral epicondylitis (LE), depending on the tasks performed by neurosurgeons, and to determine whether it can be accepted as an occupational disease depending on its frequency. MATERIAL AND METHODS: All neurosurgery specialists enrolled in the Turkish Neurosurgical Society website were prospectively included. A questionnaire form was shared, and the subsequent responses were recorded. Those who provided incomplete responses were excluded from the study. The respondents diagnosed with LE were recorded. Exclusion criteria were investigated on complaints of pain. They were examined by an orthopedics and traumatology specialist with application of Thomsen test and necessary maneuvers. RESULTS: The study was conducted with 216 neurosurgeons. Those with more than 30 operations per month (p=0.002), those with a specialization duration of 10-20 years and > 20 years (p=0.001), and those who specialized in spinal surgery (p=0.014) had a significantly higher prevalence of epicondylitis. Considering the relationship between lumbar/thoracic pedicle screw insertion and epicondylitis, the epicondylitis diagnosis rate was significantly higher in physicians inserting 20â€"60 screws per month than those inserting < 20 screws (p=0.009). CONCLUSION: LE frequently occurs in neurosurgeons who regularly perform spinal instrumentation and appears to be an occupational disease. However, data obtained during the current study should be combined with findings from case-control studies of neurosurgeons.

A long-term follow-up study of anterior tibial allografting and instrumentation in the management of thoracolumbar tuberculous spondylitis.

OBJECT: The purpose of this study was to determine the efficacy of anterior instrumentation following radical debridement and tibial allografting and its long-term progression in patients with multilevel spinal tuberculosis. METHODS: This prospective observational study was undertaken to analyze 22 patients with multilevel spinal tuberculosis (Pott disease) who underwent anterior radical debridement, decompression, and fusion using anterior spinal instrumentation and tibial allograft replacement between 1999 and 2001. Clinical outcomes were assessed using the American Spinal Injury Association (ASIA) Impairment Scale and a visual analog scale (VAS). Preoperative and postoperative plain radiographs were obtained, and the focal kyphotic angle of the surgically treated spinal segments and the overall sagittal and coronal contours of the thoracic and lumbar spine were evaluated in all patients. RESULTS: The mean follow-up time was 84 months (range 36-96 months). All patients demonstrated clinical healing of the tuberculosis infection. All patients showed evidence of successful bone fusion. The mean late postoperative kyphosis correction was 74% (range 63-91%). On average, 2 degrees (range 0-5 degrees ) of loss of correction was noted in the local kyphotic angle postoperatively in late follow-up findings. Evaluation of the surgical effect on sagittal global contours showed a significant correction rate in thoracic, thoracolumbar, and lumbar regions. The mean late postoperative coronal plane alignment correction was 99%. The ASIA Impairment Scale scores demonstrated significant improvement in late follow-up results in our series. Surgical decompression also resulted in a dramatic reduction of overall pain in all patients (late postoperative VAS score 1.61 +/- 0.81). CONCLUSIONS: Anterior tibial allografting and instrumentation provide correction of the curvature, prevention of further deformation, improvement of sagittal and coronal balance, and restoration of neurological function in patients with spinal tuberculosis.

Spinal cord compression caused by a brown tumor at the cervicothoracic junction.

BACKGROUND CONTEXT: Brown tumors are classic benign skeletal manifestations of hyperparathyroidism, but the spine involvement is very rare. Spinal reconstruction in these patients is controversial because of the severe osteoporosis and impaired bone healing. Of the reported 12 cases of spinal brown tumors in the literature, only in 5 were reconstructions with bone graft used. PURPOSE: To describe our management in a patient with brown tumor and also to review the previous published cases. STUDY DESIGN: Case report. METHODS: A case of a brown tumor in the T1 vertebra of a 72-year-old male patient is described. He had a previous diagnosis of secondary hyperthyroidism caused by renal failure. First, posterior transpedicular open biopsy was performed for the diagnosis and also for the decompression of the root causing brachialgia. After the diagnosis of a brown tumor, the patient was reoperated through anterior approach for total tumor removal and reconstruction of the spine. An autolog 3-cortical iliac crest strut graft was used for fusion, and medical treatment of hyperparathyroidism was given immediately after the operation. Decompression of spinal canal and fusion of bone graft was shown by a computed tomography scan 1 year after the operation. RESULTS: Complete resolution of the complaints of the patient and fusion of the graft were achieved. CONCLUSION: The determination of a spinal tumor in a patient with renal failure and hyperparathyroidism should bring to mind the probability of a brown tumor. Although it is of a benign nature, it can cause severe neurologic deficit because of spinal compression. The recommended treatment modality is surgical resection of the tumor, spinal reconstruction, and aggressive treatment of hyperparathyroidism both with parathyroidectomy and medically.

Midterm outcome after unilateral approach for bilateral decompression of lumbar spinal stenosis: 5-year prospective study.

The aim of our study is to evaluate the results and effectiveness of bilateral decompression via a unilateral approach in the treatment of degenerative lumbar spinal stenosis. We have conducted a prospective study to compare the midterm outcome of unilateral laminotomy with unilateral laminectomy. One hundred patients with 269 levels of lumbar stenosis without instability were randomized to two treatment groups: unilateral laminectomy (Group 1), and laminotomy (Group 2). Clinical outcomes were assessed with the Oswestry Disability Index (ODI) and Short Form-36 Health Survey (SF-36). Spinal canal size was measured pre- and postoperatively. The spinal canal was increased to 4-6.1-fold (mean 5.1 +/- SD 0.8-fold) the preoperative size in Group 1, and 3.3-5.9-fold (mean 4.7 +/- SD 1.1-fold) the preoperative size in Group 2. The mean follow-up time was 5.4 years (range 4-7 years). The ODI scores decreased significantly in both early and late follow-up evaluations and the SF-36 scores demonstrated significant improvement in late follow-up results in our series. Analysis of clinical outcome showed no statistical differences between two groups. For degenerative lumbar spinal stenosis unilateral approaches allowed sufficient and safe decompression of the neural structures and adequate preservation of vertebral stability, resulted in a highly significant reduction of symptoms and disability, and improved health-related quality of life.

Efficacy of unilateral laminectomy for bilateral decompression in lumbar spinal stenosis.

OBJECTIVE: We have conducted a prospective study to evaluate the results and effectiveness of bilateral decompression via a unilateral laminectomy in 50 patients with 98 levels of degenerative lumbar spinal stenosis without instability. METHODS: Clinical outcomes were assessed using the Visual Analog Scale, Oswestry Disability Index, Short Form-36, and subjective Satisfaction Measurement. RESULTS: Adequate decompression was achieved in all patients. The mean follow-up time was 22.8 months (range 19 - 47 months). Surgical decompression resulted in a dramatic reduction of overall pain in all patients (late postoperative VAS score was 2.16 +/- 0.81). The ODI scores decreased significantly in early and late follow-up evaluations and the SF-36 scores demonstrated significant improvement in late follow-up results in our series. Patient satisfaction rate was 94%, and its improvement rate was 96%. CONCLUSION: For degenerative lumbar spinal stenosis with or without mild degenerative spondylolisthesis, the unilateral approach allowed sufficient and safe decompression of the neural structures and adequate preservation of vertebral stability, resulted in a highly significant reduction of symptoms and disability, and improved health-related quality of life.

Use of decorin to prevent epidural fibrosis in a post-laminectomy rat model.

The formation of epidural fibrosis adjacent to the dura mater is a complex multi-step process that is associated with a marked reduction in tissue cellularity and the excessive deposition of extracellular matrix components. Extensive epidural fibrosis is a major cause of post-laminectomy syndrome. Decorin strongly inhibits fibrosis formation in various tissues via blockade of transforming growth factor-ß1. The aim of this study was to investigate the effects of a topical application of decorin on the formation of epidural fibrosis in a rat laminectomy model. Twenty-four female Wistar albino rats (250-350 g) were equally and randomly divided into three groups (control, spongostan and decorin). Laminectomy was performed between the L3 and L5 levels in all rats. The dura mater was directly exposed to spongostan soaked with saline (2 cc/kg) or decorin (100 µg/kg). Four weeks later, the laminectomized spine of the rats was completely removed between the L3 and L5 levels. The extent of the epidural fibrosis and arachnoidal involvement was histopathologically evaluated and graded. Our data revealed that epidural fibrosis was significantly reduced in the group treated with decorin compared to the spongostan and control groups (P<0.05). Our study demonstrates that the topical application of decorin can be effective in reducing the formation of epidural fibrosis in a simple laminectomy rat model.

[Occipital condyle fractures: a case report]. / Oksipital kondil kiriklari: Bir olgu sunumu.

Occipital condyle fractures are rare, and conservative treatment is sufficient for many cases. Surgical treatment may be required if the condyle fracture is accompanied by atlantooccipital dislocation. Unfortunately, condyle fracture generally cannot be diagnosed with X-ray in the emergency department. Recently, computed tomography scans have been used more frequently, and enable easier diagnosis of these types of fractures. In this report, we describe a patient who admitted to our emergency department after a major trauma. She complained of neck pain, and maxillofacial trauma was more evident. Her cervical X-rays were normal, but cervical computed tomography revealed unilateral occipital condyle fracture.

The effect of etanercept on spinal epidural fibrosis in a postlaminectomy rat model.

AIM: The formation of epidural fibrosis adjacent to the dura mater after posterior spinal surgery is a normal reaction of the body to surgery. Extensive epidural fibrosis is one of the important causes of postlaminectomy syndrome. Etanercept inhibits tumor necrosis factor-alpha and decreases fibroblast migration. Thus, etanercept prevents the formation of fibrosis. The aim of this study was to investigate the effects of topical application of etanercept on epidural fibrosis after laminectomy in a rat model. MATERIAL AND METHODS: Twenty-four Wistar rats were equally and randomly divided into three groups (control, spongostan and etanercept). Laminectomy was performed between L3 and L5 in all the rats. Spongostan soaked with saline (0.1 mg/kg) and etanercept (300 µg/kg) was directly exposed to and left on the dura mater. Four weeks later, the vertebral columns of the rats were removed en bloc between T10 and L5, and epidural fibrosis and arachnoidal involvement were evaluated and graded histopathologically. RESULTS: Our data revealed that epidural fibrosis was reduced significantly in the rats treated with etanercept, compared to the control groups (p < 0.05). CONCLUSION: Our study demonstrated that topical application of etanercept can be effective in reducing epidural fibrosis in rats after laminectomy.

The impact of automatic retractors on the esophagus during anterior cervical surgery: an experimental in vivo study in a sheep model.

OBJECT: Postoperative dysphagia is a well-recognized complication of the anterior surgical approach to the cervical spine. However, its incidence and etiology remain unknown. The aim of this study was to investigate the impact of automatic retractor use on the esophagus and to describe the related pathological changes that might occur during cervical spine surgery. METHODS: A single-level cervical discectomy was performed via an anterior approach in 16 skeletally mature female sheep. Continuous retraction was applied with an automatic retractor system during surgery. The sheep model was chosen because of anatomical similarities to the human esophagus. The esophageal tract in every animal was examined using contrast radiographic examination. Eight animals were killed 3 days after the operation (Group 1). The remaining sheep were killed 4 weeks after the operation (Group 2). The esophagi were removed for histopathological study, which was performed using H & E and Masson trichrome staining. The changes in esophageal innervation were examined with nicotinamide adenine dinucleotide diphosphate-diaphorase histochemical staining. RESULTS: Only 1 animal (a Group 1 sheep) demonstrated any postoperative radiographic abnormality. In Group 1 sheep, histopathological study of the esophagi at the treated level revealed edema between the muscular fibers in the outer longitudinal and inner circular layers of the muscularis propria. At some points, obvious signs of vascular congestion, vascular damage, and inflammation were observed. In the Group 2 animals, there was mild-to-moderate fibrosis extending from the outer surface of the esophagus to the longitudinal layers of the muscularis propria in the area to which retraction had been applied. Enzyme-histochemical staining revealed the presence of normal myenteric plexus and ganglion cells, and nitrergic innervation in all parts of the esophagus wall. CONCLUSIONS: The results of this study demonstrate that direct pressure induced by the medial retractor blade on the esophagus wall leads to local injury. Postoperative dysphagia in human patients who have undergone anterior cervical spine surgery could be a clinical manifestation of this phenomenon.