Evidence that osteogenic and neurogenic differentiation capability of epidural adipose tissue-derived stem cells was more pronounced than in subcutaneous cells

Background/aim: The management of dura-related complications, such as the repairment of dural tears and reconstruction of large dural defects, remain the most challenging subjects of neurosurgery. Numerous surgical techniques and synthetic or autologous adjuvant materials have emerged as an adjunct to primary dural closure, which may result in further complications or side effects. Therefore, the subcutaneous autologous free adipose tissue graft has been recommended for the protection of the central nervous system and repairment of the meninges. In addition, human adipose tissue is also a source of multipotent stem cells. However, epidural adipose tissue seems more promising than subcutaneous because of the close location and intercellular communication with the spinal cord. Herein, it was aimed to define differentiation capability of both subcutaneous and epidural adipose tissue-derived stem cells (ASCs). Materials and methods: Human subcutaneous and epidural adipose tissue specimens were harvested from the primary incisional site and the lumbar epidural space during lumbar spinal surgery, and ASCs were isolated. Results: The results indicated that both types of ASCs expressed the cell surface markers, which are commonly expressed stem cells; however, epidural ASCs showed lower expression of CD90 than the subcutaneous ASCs. Moreover, it was demonstrated that the osteogenic and neurogenic differentiation capability of epidural adipose tissue-derived ASCs was more pronounced than that of the subcutaneous ASCs. Conclusion: Consequently, the impact of characterization of epidural ASCs will allow for a new understanding for dural as well as central nervous system healing and recovery after an injury.

Stem cell/cellular interventions in human spinal cord injury: Is it time to move from guidelines to regulations and legislations? Literature review and Spinal Cord Society position statement.

PURPOSE: In preclinical studies, many stem cell/cellular interventions demonstrated robust regeneration and/or repair in case of SCI and were considered a promising therapeutic candidate. However, data from clinical studies are not robust. Despite lack of substantial evidence for the efficacy of these interventions in spinal cord injury (SCI), many clinics around the world offer them as "therapy." These "clinics" claim efficacy through patient testimonials and self-advertisement without any scientific evidence to validate their claims. Thus, SCS established a panel of experts to review published preclinical studies, clinical studies and current global guidelines/regulations on usage of cellular transplants and make recommendations for their clinical use. METHODS: The literature review and draft position statement was compiled and circulated among the panel and relevant suggestions incorporated to reach consensus. This was discussed and finalized in an open forum during the SCS Annual Meeting, ISSICON. RESULTS: Preclinical evidence suggests safety and clinical potency of cellular interventions after SCI. However, evidence from clinical studies consisted of mostly case reports or uncontrolled case series/studies. Data from animal studies cannot be generalized to human SCI with regard to toxicity prediction after auto/allograft transplantation. CONCLUSIONS: Currently, cellular/stem cell transplantation for human SCI is experimental and needs to be tested through a valid clinical trial program. It is not ethical to provide unproven transplantation as therapy with commercial implications. To stop the malpractice of marketing such "unproven therapies" to a vulnerable population, it is crucial that all countries unite to form common, well-defined regulations/legislation on their use in SCI. These slides can be retrieved from Electronic Supplementary Material.

A developmental study of glutamatergic neuron populations in the ventrobasal and the lateral geniculate nucleus of the thalamus: Comparing Genetic Absence Rats from Strasbourg (GAERS) and normal control wistar rats.

An imbalance of GABAergic inhibition and glutamatergic excitation is suspected to be the cause of absence epileptic seizures. Absence seizures are known to be generated in thalamocortical circuitry. In the present study we used light microscopy immunohistochemistry to quantify the density of glutamate+ve neurons at two developmental stages (P10 and P60) in two thalamic nuclei, the ventrobasal (VB) and lateral geniculate nucleus (LGN) in Wistar rats and compared the results with similar data obtained from genetic absence epilepsy rats from Strasbourg (GAERS). Rats were perfused transcardially with glutaraldehyde and paraformaldehyde fixative, then samples from VB and LGN were removed from each animal and sectioned. The glutamatergic neurons were labelled using light-microscopic glutamate immunohistochemistry. The disector method was used to quantify the glutamate+ve neurons in VB and LGN of GAERS and Wistar rats. The data were statistically analyzed. The distribution of the glutamate+ve neurons in the VB thalamic nucleus showed a significant reduction in the neuronal profiles per unit thalamic area from P10 to P60 in both Wistar and GAERS. The decrease was greater in the GAERS compared to the Wistar animals. However, in the LGN no reduction was observed either in the Wistar or in the GAERS. Comparing the density of glutamate+ve neurons in the VB thalamic nucleus of P10 of Wistar animals with of P10 GAERS showed statistically significant greater densities of these neurons in GAERS than in the Wistar rats. However no significant difference was present at P60 between the Wistar and GAERS animals. The disproportional decrease in GAERS may be related to the onset of absence seizures or may be related to neurogenesis of absence epilepsy.

Punica granatum L. Juice Attenuates Experimental Cerebral Vasospasm in the Rabbit Subarachnoid Hemorrhage Model: A Basilar Artery Morphometric Study and Apoptosis.

Background This study investigated the effect of Punica granatum L. (pomegranate) juice on the rabbit basilar artery in an experimental subarachnoid hemorrhage (SAH) model. Methods Eighteen adult male New Zealand white rabbits were randomly divided into three groups: a control group (n = 6), SAH group (n = 6), and SAH + treatment group (n = 6). Basilar artery diameter was measured with magnetic resonance angiography (MRA) in all groups at the beginning of the study. Experimental SAH was created by injecting autologous arterial blood into the cisterna magna. In the treatment group, the subjects were administered a daily dose of 30 ml/kg pomegranate juice via gastric gavage for 4 days after the SAH. The SAH group and SAH + treatment group underwent cerebral MRA after 72 hours. After a neurologic score assessment, all the animals were killed. The wall thickness and lumen area of the basilar artery were measured histometrically in all groups, and the apoptotic cell percentage in the artery was identified. The mean diameter of the basilar artery during MRA was measured. Results Pomegranate improved neurologic functions compared with the SAH group (p < 0.01). The mean basilar artery diameter on MRA in the SAH + treatment group was larger than in the SAH group and smaller than in the control group (p < 0.01 and p < 0.05, respectively). The mean vessel wall thickness value in the SAH + treatment group was lower than in the SAH group (p < 0.01), whereas there was no difference between the control and the SAH + treatment group (p > 0.05). The apoptotic cell rate in the SAH + treatment group was significantly lower than in the SAH group (p < 0.001). Evaluation of the basilar artery luminal area showed no difference between the three groups (p > 0.05). Discussion Pomegranate was shown to have a vasospasm- attenuating effect on the basilar artery in the rabbit SAH model for the first time in our study.

Esophageal perforation after anterior cervical surgery: a review of the literature for over half a century with a demonstrative case and a proposed novel algorithm.

PURPOSE: To review relevant data for the management of esophageal perforation after anterior cervical surgery. METHODS: A case of delayed esophageal perforation after anterior cervical surgery has been presented and the relevant literature between 1958 and 2014 was reviewed. A total of 57 papers regarding esophageal perforation following anterior cervical surgery were found and utilized in this review. RESULTS: The treatment options for esophageal perforation after anterior cervical surgery were discussed and a novel management algorithm was proposed. CONCLUSION: Following anterior cervical surgery, patients should be closely followed up in the postoperative period for risk of esophageal perforation. Development of symptoms like dysphagia, pneumonia, fever, odynophagia, hoarseness, weight loss, and breathing difficulty in patients with a history of previous anterior cervical surgery should alert us for a possible esophageal injury. Review of the literature revealed that conservative treatment is advocated for early and small esophageal perforations. Surgical treatment may be considered for large esophageal defects.

Current and future medical therapeutic strategies for the functional repair of spinal cord injury.

Spinal cord injury (SCI) leads to social and psychological problems in patients and requires costly treatment and care. In recent years, various pharmacological agents have been tested for acute SCI. Large scale, prospective, randomized, controlled clinical trials have failed to demonstrate marked neurological benefit in contrast to their success in the laboratory. Today, the most important problem is ineffectiveness of nonsurgical treatment choices in human SCI that showed neuroprotective effects in animal studies. Recently, attempted cellular therapy and transplantations are promising. A better understanding of the pathophysiology of SCI started in the early 1980s. Research had been looking at neuroprotection in the 1980s and the first half of 1990s and regeneration studies started in the second half of the 1990s. A number of studies on surgical timing suggest that early surgical intervention is safe and feasible, can improve clinical and neurological outcomes and reduce health care costs, and minimize the secondary damage caused by compression of the spinal cord after trauma. This article reviews current evidence for early surgical decompression and nonsurgical treatment options, including pharmacological and cellular therapy, as the treatment choices for SCI.

Neuroprotective effect of magnesium sulfate and dexamethasone on intrauterine ischemia in the fetal rat brain: ultrastructural evaluation.

AIM: The aim of this study was to investigate the neuroprotective effect of magnesium sulfate and dexamethasone on oxidative damage in intrauterine ischemia. MATERIAL AND METHODS: In this study, 19-day pregnant rats were divided into five groups. Fetal brain ischemia was achieved in the ischemia/ reperfusion (I/R) group by bilaterally closing the utero-ovarian artery with aneurysm clips for 30 min and subsequently removing the aneurysm clips for 60 min for reperfusion. Mg (600 mg/kg) and dexamethasone (0.25 mg/kg) were administered 20 min before the I/R insult. The lipid peroxidation in the brain tissue was determined by the concentration of thiobarbituric acid reactive substances (TBARS). The mitochondrial score was calculated after an evaluation with electron microscopy. RESULTS: Both the electron microscope and TBARS data showed a significant difference between the control and I/R groups. The Mg and dexamethasone treatment groups exhibited significantly lower TBARS values compared to the IR group. Similarly, the mitochondrial scores in the Mg and dexamethasone treatment groups were significantly lower than those in the I/R group. CONCLUSION: Result showed that magnesium sulfate and dexamethasone prevent lipid peroxidation and reduce mitochondrial injury thus suggests neuroprotective effects in fetal rat brain in intrauterine ischemia-reperfusion (I/R) injury.

The therapeutic effects of melatonin and nimodipine in rats after cerebral cortical injury.

AIM: Secondary brain injury starts after the initial traumatic impact and marked by an increase in the intracellular calcium concentrations.This cascadeeventually results in membrane lipid peroxidation and neuronal cell death. MATERIAL AND METHODS: We investigated the neuro-protective effects of nimodipine and melatonin in 38 rats after 6 hours of head trauma using the cortical impact injury model of Marmarou. RESULTS: Brain water in the melatonin-given group decreased significantly comparing to that of control group the brain water in the nimodipine given group increased significantly comparing to that of trauma group. Histopathologically, brain edema was significantly low in melatonin-administered group comparing to that of control group while there were no changes in brain edema in the nimodipine given group and in the group that both nimodipine and melatonin were administered in combination. MDA levels in the brain tissues were significantly lower in the melatonin and nimodipine groups comparing to those of trauma and control group however this difference was by far significant in melatonin group comparing to nimodipine group. CONCLUSION: Melatonin appears to have neuro-protective effects on the secondary brain damage while nimodipine and nimodipine plus melatonin combination did not show such neuro-protective effects on the secondary brain injury.

Neuroprotective effects of propofol, thiopental, etomidate, and midazolam in fetal rat brain in ischemia-reperfusion model.

PURPOSE: The aim of this study was to investigate the neuroprotective effects of propofol, thiopental, etomidate, and midazolam as anesthetic drugs in fetal rat brain in the ischemia-reperfusion (IR) model. METHODS: Pregnant rats of day 19 were randomly allocated into eight groups. Fetal brain ischemia was induced by clamping the utero-ovarian artery bilaterally for 30 min and reperfusion was achieved by removing the clamps for 60 min. In the control group, fetal rat brains were obtained immediately after laparotomy. In the sham group, fetal rat brains were obtained 90 min after laparotomy. In the IR group, IR procedure was performed. No treatment was given in the IR group. One milliliter intralipid solution, 40 mg/kg propofol, 3 mg/kg thiopental, 0.1 mg/kg etomidate, and 3 mg/kg midazolam was administered intraperitoneally in the vehicle group, propofol group, thiopental group, etomidate group, and midazolam group, respectively, 20 min before IR procedure. At the end of the reperfusion period, the whole brains of the fetal rats were removed for evaluation of thiobarbituric acid reactive substances and for examination by electron microscopy. RESULTS: According to lipid peroxidation data, all the anesthetic drugs provide neuroprotection; however, ultrastructural findings and mitochondrial scoring confirms that only propofol and midazolam provides a strong neuroprotective effect. CONCLUSIONS: Propofol and midazolam may be used to protect fetal brain in case of acute fetal distress and hypoxic injury as a first choice anesthetic drug in cesarean delivery.

An attempt to treat patients who have injured spinal cords with intralesional implantation of concentrated autologous bone marrow cells.

BACKGROUND AIMS: Spinal cord injury is common among young subjects involved in motor vehicle accidents. Mechanisms and attempts to reverse post-traumatic pathophysiologic consequences are still being investigated. Unfortunately no effective and well-established treatment modality has been developed so far. The regeneration capability of the human nervous system following an injury is highly limited. METHODS: The study involved four patients (two male, two female) who had suffered spinal cord injury as a result of various types of trauma. On neurologic examination, all the patients were determined to be in American Spinal Injury Association (ASIA) grade A. All patients were treated with decompression, stabilization and fusion for vertebral trauma anteriorly, as well as intralesional implantation of cellular bone marrow concentrates using a posterior approach 1 month after the first operation. The patients were then treated and followed-up in the physical rehabilitation clinic. RESULTS: At the end of the post-operative 1-year follow-up, two of the patients were classified as ASIA C while one was classified as ASIA B. One patient showed no neurologic change; none of the patients suffered from any complications or adverse effects as a result of intralesional application of bone marrow cells. CONCLUSIONS: The results of this experimental study show the potential contribution of intralesional implantation of bone marrow to neuronal regeneration in the injured spinal cord, with neuronal changes. In light of the results of this experimental study, the potential for regenerative treatment in injuries of the human spinal cord is no longer a speculation but an observation.

Faun tail nevus and spinal dysraphism: cosmetic improvement with alexandrite laser epilation.

Faun-tail presents as an abnormal lumbosacral hypertrischosis and may be associated with spinal dysrasphism. In addition to the problems due to spinal anomalies, patient's physico-social life may also be affected. Here, we report a case of 13 years old female patient with Faun-tail in association with sypinal dysraphism, in which cosmetic improvement was achieved with the help of Alexandrite laser. Alexandrite laser can be the method of choice for permanent hair removal method due to its safe, effective and easy to apply properties.

Effect of granulocyte-colony stimulating factor on spinal cord tissue after experimental contusion injury.

The purpose of this study was to investigate the early effects of granulocyte-colony stimulating factor (G-CSF) on myeloperoxidase (MPO) activity, lipid peroxidation (LPO) and ultrastructural findings in rats after spinal cord injury (SCI). We also compared the effects of G-CSF and methylprednisolone sodium succinate (MPSS). Wistar rats were divided into four groups: control, SCI alone (50 g/cm weight drop trauma), SCI+MPSS (30 mg/kg), and SCI+G-CSF (50 µg/kg). Administration of G-CSF and MPSS significantly decreased LPO (p < 0.05) and MPO activity (p < 0.05) in the first 24 hours. MPSS was more effective than G-CSF in reducing LPO (p < 0.05) and in minimizing ultrastructure changes. The results of this study indicate that G-CSF exerts a beneficial effect by decreasing MPO activity and LPO and may reduce tissue damage in the first 24 hours after SCI. Our findings do not exclude the possibility that G-CSF has a protective effect on spinal cord ultrastructure after the first 24 hours following SCI.

Cranial ossifying fibroma causing visual disorder.

Fibrous lesions of the head and the maxillofacial region are generally slow-developing benign tumors that may aggressively take course in clinical terms. These locally destructive lesions show a high recurrence rates unless they are removed gross totally. Sarcomatoid degeneration is also reported to develop in recurring lesions. Difficulties in the diagnosis, classification, and treatment make this entity complex for several years. These tumors are frequently seen among children and young adults. The maxilla and the mandibula are the 2 most common sites that the tumor originates. In our article, we discuss a 59-year-old man whose condition was diagnosed as an ossified fibroma revealing craniofacial extension. Accompanied by literature findings, it has been underlined that, as well as with the pathologic criteria, clinical features and radiologic images should be evaluated together for a specific diagnosis in fibrous lesions.

Paraplegia associated with spinal hydatid cyst: a case report.

STUDY DESIGN: Case report. OBJECTIVES: To report a case with paraplegia caused by spinal hydatid cyst. SUMMARY OF BACKGROUND DATA: Hydatid cyst is a disease caused by larval Echinococcus granulosus tapeworm. Spinal hydatid cyst rarely leads to severe neurologic problems. METHODS: A 34-year-old male patient was referred to our outpatient clinic due to back and low back pain, progressive weakness and numbness in both lower extremities, and a prediagnosis of lumbar disc hernia. He had spastic paraplegia, and thorax magnetic resonance imaging revealed a lobulated cystic lesion with extradural intraspinal localization. RESULTS: After surgery and following 2 months of rehabilitation program, the patient showed a dramatic clinical improvement. CONCLUSION: By this case, it is emphasized that spinal hydatid cyst should come to mind in the differential diagnosis of spinal cord compression, and the importance of prevention, early diagnosis, and treatment is highlighted because of high mortality and morbidity.

Use of pimecrolimus to prevent epidural fibrosis in a postlaminectomy rat model.

OBJECT: Epidural fibrosis is the scar tissue formed over the dura mater after a laminectomy. Extensive epidural fibrosis may be an important underlying cause of failed back syndrome. Pimecrolimus, an ascomycin derivative, is one of the new classes of immunomodulating macrolactams and was specifically developed for the treatment of inflammatory diseases. This study examined the preventive effects of the local application of pimecrolimus in minimizing spinal epidural fibrosis in a rat laminectomy model. METHODS: Thirty Wistar rats were divided into 3 equal groups: control, mitomycin C (MMC), and pimecrolimus groups. Each rat underwent a laminectomy at the L-3 lumbar level. In the experimental groups, a cotton pad soaked with MMC (0.5 mg/ml) or 5 mg pimecrolimus was placed on the exposed dura mater. No treatment was performed in the control group rats. Thirty days after surgery, the rats were killed and the dura mater thickness, epidural fibrosis, and arachnoidal involvement were quantified. RESULTS: The mean dura thickness was measured at 9.28 +/- 3.39 microm in the MMC group and at 8.69 +/- 2.32 microm in the pimecrolimus group, compared with 14.70 +/- 4.14 microm in the control group. In addition, the epidural fibrosis and arachnoidal involvement were reduced significantly in the treatment groups compared with the control group. CONCLUSIONS: In this animal model, it was shown that locally applied pimecrolimus effectively reduces epidural fibrosis and dural adherence in rats that underwent lumbar laminectomy. Mitomycin C was equally effective as pimecrolimus in reducing epidural fibrosis and dural adherence in this study.

Attempted suicide with screw penetration into the cranium.

Intracranial foreign bodies are usually secondary to penetrating injuries. Nails, knives, screwdrivers, sewing needles, bullets, and shrapnel have been described related to penetrating brain injury. In this report, we present a 34-year-old prisoner with an intracranial screw located in the right parietal lobe. The screw was used by prisoner in an attempted suicide. A right parietal craniectomy was performed, and the screw was removed successfully. It is important to know the type of penetrating brain injury preoperatively in order to determine the best surgical approach to remove the foreign body settled in the brain. A long-term radiological assessment should be performed to detect any future complications, such as a cerebral abscess.

Glioblastoma multiforme mimicking arteriovenous malformation.

Glioblastoma multiforme is the most common intracranial neoplasm of all primary central nervous system tumors. Glial tumors can present in different forms. Intracranial hemorrhage may occur in all central nervous system tumors to a varying degree and extent and may even be massive. A 58-year-old man presented with intraparenchymal hemorrhage manifesting as severe headache and vomiting. Cranial computed tomographic scans revealed a right posterior temporoparietal intraparenchymal hemorrhage. Cerebral angiography revealed a 3 x 2 cm right inferior parietal arteriovenous malformation. The patient underwent surgical treatment with a diagnosis of arteriovenous malformation. Postoperatively, the histological diagnosis was glioblastoma. Glioblastoma may mimic an arteriovenous malformation. Close follow-up of such patients is essential.

The importance of vertebral artery proximity to the odontoid process during anterior odontoid approaches.

The proximity of the vertebral artery (VA) to the odontoid process makes it vulnerable to injury during surgery. Knowledge of the quantitative anatomy of the VA groove is therefore necessary. In this study we assessed the spatial relationship between the VA and the odontoid process on cadavers by direct measurement and in patients by CT angiography. Our goal was to measure the distances from the VA and vertebrobasilar junction to the odontoid tip. The VA and odontoid process of 10 craniocervical cadavers ("cadavers") and of 20 patients were evaluated and average measurements obtained. The measured parameters were: (i) distance from the right VA to the odontoid tip (right VA-odontoid tip); (ii) distance from the left VA to the odontoid tip (left VA-odontoid tip), and (iii) distance from the vertebrobasilar junction to the odontoid tip (vertebrobasilar-odontoid tip). On the cadavers, the right VA-odontoid tip distance was 11.55mm, the left VA-odontoid tip was 11.02mm, and the vertebrobasilar junction-odontoid tip distance was 24.55mm. In patients, using CT angiography, the right VA-odontoid tip distance was 11.47mm and the left VA-odontoid tip distance was 11.50mm. The VA-odontoid tip distance is important in anterior odontoid approaches. Since the odontoid process may be in close contact with the VA, the relationship between them should be evaluated preoperatively in all candidates for odontoid surgery using three-dimensional CT angiography.