Can chlorogenic acid reduce oxidative stress and in an experimental spinal cord injury?

BACKGROUND: We aimed to investigate antioxidant and neuroprotective properties of chlorogenic acid in spinal cord injury (SCI). METHODS: Twenty-one rats were divided into three groups. Laminectomy was performed in group L (n=7), spinal cord trauma was induced in group T (n=7), and spinal cord trauma was induced and chlorogenic acid treatment was started in group C (n=7). Blood samples were collected to analyze baseline values and the 12th h, 1st day, 3rd day, and 5th day catalase, native thiol (NT), total thiol (TT), disulfide (SS), SS/TT, SS/NT, and NT/TT levels. Functional analysis with Basso-Beattie and Bresnahan scores was performed at the same time points. Total antioxidant status (TAS), total oxidative stress, oxidative stress index, and cyclooxygenase-2 (Cox-2) were examined in the spinal cord of rats euthanized on day 7; results were statistically analyzed. RESULTS: On day 7, catalase levels in Group C were significantly higher than baseline levels, whereas those in Group T were significantly lower than baseline levels; Group L showed no significant difference (p=0.008). SS values on day 7 were lower in Group T than in Groups C and L. Group C showed the lowest decrease in NT/TT level after trauma. On day 7, SS/TT level was high in Group T but stable in Groups C and L (p=0.04). Histopathological examination revealed significantly lower Cox-2 and TAS levels in Group C than in Group T (p=0.003, p=0.017, respectively). CONCLUSION: In this study, SCI was primarily examined through thiol-SS balance, and it was demonstrated by experimental models that chlorogenic acid has antioxidant and neuroprotective effects in SCI.

Anti-inflammatory and antioxidative effects of genistein in a model of spinal cord injury in rats.

Background: Neurological damage from spinal cord injury (SCI) is a result of primary mechanical injury and secondary damage from oxidative stress and neuroinflammation. Although genistein has been shown to have potent antioxidant and anti-inflammatory effects in studies of brain injury, its effect on secondary damage in SCI has remained unknown. Objective: To determine effects of genistein in a model of SCI in rats. Methods: We divided 21 rats evenly into 3 groups, a control group, in which only a laminectomy was performed; a trauma group in which SCI was induced; and a genistein group in which genistein was administered subcutaneously after SCI. The rats were assessed using a Basso-Beattie and Bresnahan functional score at the 12th hour and on the 1st, 3rd, 5th, and 7th days. Biochemical analyses were conducted at the same time points to determine the serum levels of catalase, ischemia-modified albumin (IMA), disulfide (SS), total thiol (TT), native thiol (NT), disulfide/total thiol (SS/TT), and native thiol/total thiol (NT/TT). Total oxidant and antioxidant capacity, and oxidative stress index were determined in spinal cord tissue obtained on the 7th day together with immunohistochemistry for cyclooxygenase-2 levels. Result: Catalase activity on the 7th day was significantly (P = 0.001) higher in the genistein-treated rats than in other groups, and IMA levels became stable earlier (3rd day) in the genistein group. SS values were significantly (P = 0.004) lower in the genistein group. NT/TT ratio were significantly (P = 0.049) higher in the genistein-treated rats on the 7th day. Conclusion: Genistein has antioxidant, anti-inflammatory, and protective effects in a model of SCI in rats and warrants further study.

Neuroprotective Efficiency of Cyclosporine After Traumatic Brain Injury in Rats.

AIM: To evaluate the possible neuroprotective effects of systemic administration of cyclosporine (Cyclosporin A) after traumatic brain injury in rats. MATERIAL AND METHODS: The modified Feeney method was used as the trauma model in male Sprague Dawley rats. After the trauma, 20 mg/kg of cyclosporine was administered to the one group of the rats (n=12) intraperitoneally. Twenty-four hours after injury, the subjects were sacrificed, and brain samples were removed. The level of brain edema was evaluated through the wet-dry weight method, the lipid peroxidation ratio, and histological examination by transmission electron microscopy. RESULTS: The level of brain edema and lipid peroxidation ratio significantly decreased in the rats that received cyclosporine. Ultrastructural neurodestruction was graded, and a comparison of the scores between the experimental groups revealed significant neuroprotective effects of cyclosporine. CONCLUSION: The results demonstrated that systemic administration of cyclosporine produces a statistically significant decrease in both the level of brain edema and lipid peroxidation ratio when compared with "no treatment". Cyclosporine, which is regularly used as an immunosuppressant agent, is also known to prevent opening of the mitochondrial permeability transition pore by unbinding mitochondrial matrix cyclophilin. Regulation of transition pore for mitochondrial permeability by cyclosporine implies that mitochondrial dysfunction following traumatic brain injury is an important event in the progressive loss of neuronal tissue.

Composite nanofibers incorporating alpha lipoic acid and atorvastatin provide neuroprotection after peripheral nerve injury in rats.

Despite the new treatment strategies within the last 30 years, peripheral nerve injury (PNI) is still a worldwide clinical problem. The incidence rate of PNIs is 1 in 1000 individuals per year. In this study, we designed a composite nanoplatform for dual therapy in peripheral nerve injury and investigated the in-vivo efficacy in rat sciatic nerve crush injury model. Alpha-lipoic acid (ALA) was loaded into poly lactic-co-glycolic acid (PLGA) electrospun nanofibers which would release the drug in a faster manner and atorvastatin (ATR) loaded chitosan (CH) nanoparticles were embedded into PLGA nanofibers to provide sustained release. Sciatic nerve crush was generated via Yasargil aneurism clip with a holding force of 50 g/cm2. Nanofiber formulations were administered to the injured nerve immediately after trauma. Functional recovery of operated rat hind limb was evaluated using the sciatic functional index (SFI), extensor postural thrust (EPT), withdrawal reflex latency (WRL) and Basso, Beattie, and Bresnahan (BBB) test up to one month in the post-operative period at different time intervals. In addition to functional recovery assessments, ultrastructural and biochemical analyses were carried out on regenerated nerve fibers. L-929 mouse fibroblast cell line and B35 neuroblastoma cell line were used to investigate the cytotoxicity of nanofibers before in-vivo experiments. The neuroprotection potential of these novel nanocomposite fiber formulations has been demonstrated after local implantation of composite nanofiber sheets incorporating ALA and ATR, which contributed to the recovery of the motor and sensory function and nerve regeneration in a rat sciatic nerve crush injury model.

Critical pancreatitis management associated with hypertriglyceridemia in pregnancy in emergency service.

Because of the variable clinical features of acute pancreatitis, it is difficult to make a differential diagnosis in patients presenting with abdominal pain in emergency departments. Acute pancreatitis due to severe hypertriglyceridemia during pregnancy is rare but due to the increased risk of maternal and fetal mortality, diagnosis and treatment options should be known and should be performed in the emergency department, which is the first admission site. In this case report, we present a 20-year-old woman with 19 weeks pregnant who presented to the emergency department with abdominal pain and whose biochemistry parameters were high enough to give lipemic stimulation was hospitalized in the emergency intensive care unit (EICU) in the emergency department and lipid apheresis treatment was planned successfully. Lipid apheresis treatment in patients with resistant hypertriglyceridemia in the emergency department should become an easy, safe and effective option with the use of an emergency intensive care unit.

Diagnosis, Treatment, and Management Strategy of Meningioma during Pregnancy.

The most common benign tumor of the brain is meningiomas. Usually diagnosed between the ages of 40-60, they are more common in women. Studies have shown a strong relationship between hormones and malignancies. Although meningiomas are slow-growing tumors of the brain, pregnancy seems to induce its growth speed. Studies concerning meningiomas and hormone relationship may explain the reason why symptoms during pregnancy flare. More specifically, the estrogen and progesterone receptor may take an active role through signal transduction in inducing the growth of the tumor. Thus, the dilemma of pregnancy + meningioma arises. In this case, a 21-year-old pregnant with a giant meningioma diagnosed on the symptom of loss of sight is reported. Her pregnancy was terminated, and the tumor was excised. Her vision improved and the histopathological examination showed a progesterone receptor positive meningioma. It is a challenging decision to be made by the physician, the patient and the family when deciding if and when pregnancy should be terminated once an intracranial meningioma is diagnosed.

Chronic Subdural Hematoma Associated with Fahr Syndrome: A Clinical Association or Just a Simple Coincidence?

The Fahr syndrome (FS) is a rare degenerative neurological disorder (its prevalence is <0.5%). FS is distinguished by the presence of abnormal bilateral intracranial calcifications with a predilection for the basal ganglia, also presented by movement disorders such as parkinsonism, paresis, and speech disorders. Chronic subdural hematoma (CSH), which is typically the result of mild head trauma, is a regularly encountered condition in elderly. A 63-year-old man has referred to our clinic from another hospital with a history of mild head trauma approximately a month ago. At the time of admission, the patient's Glasgow Coma Scale point was 15 points. In the history, there was only mild ataxia and right-sided hemiparesis. The laboratory examination revealed no electrolytes level abnormalities and normal endocrinal test examinations. Computed tomography revealed bilateral calcifications of basal ganglia, dentate nuclei which were misinterpreted as intracerebral contusion; with CSH of left temporal and parietal region. The hematoma was evacuated by burr-hole drainage. The patient was discharged 5 days after the surgery. The pathophysiology of FS is still unrevealed. There are some suggestions such as secondary to local disturbance of blood-brain barrier or a calcium neuronal metabolism disorder. However, on the other hand, local blood-brain barrier disturbance would also take part in CSH pathology. We hypostasized that patients with the history of FS, who had mild head traumas, might prone to subdural collections. On the other hand, FS and CSH coexistence is very unusual. Neurosurgeons might keep in mind FS when bilateral calcifications are seen in a patient.

Localized delivery of methylprednisolone sodium succinate with polymeric nanoparticles in experimental injured spinal cord model.

With important social and economic consequences, spinal cord injuries (SCIs) still exist among major health problems. Although many therapeutic agents and methods investigated for the treatment of acute SCI, only high dose methylprednisolone (MP) is being used currently in practice. Due to the serious side effects, high dose systemic MP administration after SCI is a critical issue that is mostly considered controversial. In our study, it is aimed to develop a nanoparticle-gel combined drug delivery system for localization of MP on trauma site and eliminating dose-dependent side effects by lowering the administered dose. For this purpose, methyl prednisolone sodium succinate (MPSS) loaded polycaprolactone based nanoparticles were developed and embedded in an implantable fibrin gel. The effects of MPSS delivery system are evaluated on an acute SCI rat model, by quantification the levels of three inflammatory cytokines (interleukin-1ß, interleukin-6 and caspase-3) and assessment of the damage on ultrastructural level by transmission electron microscopy. Developed NP-gel system showed very similar results with systemic high dose of MPSS. It is believed that developed system may be used as a tool for the safe and effective localized delivery of several other therapeutic molecules on injured spinal cord cases.

Effect of Asiatic Acid on the Treatment of Spinal Cord Injury: An Experimental Study in Rats.

AIM: Spinal cord injury (SCI) is a devastating condition of the central nervous system. There is no proven therapeutic agent for the treatment of this complex disorder. Asiatic acid (AA) has been used as an anti-inflammatory and anti-oxidant agent in Eastern countries for many years. The aim of this study was to investigate the effectiveness of AA on the treatment of traumatic SCI in rats. MATERIAL AND METHODS: Thirty-two adult male Sprague-Dawley rats were divided into 4 groups as laminectomy, laminectomy+trauma, vehicle, and AA treatment groups. SCI was created by the modified Allen"s weight-drop technique. After the injury, the levels of pro-inflammatory cytokines (IL-6, IL1-Β, TNF-α) and lipid peroxidation products (MDA) were measured. Tarlov functional recovery scores were also determined for each rat. The One-way ANOVA test was used for the analysis of difference between 4 experimental groups and the groups were compared individually by Tukey-LSD post hoc analysis test (p=0.001). RESULTS: AA administration just after SCI attenuated the levels of lipid peroxidation products (MDA) and pro-inflammatory cytokines (TNF-α, IL1Β). It also increased the Tarlov functional recovery scores of the rats. CONCLUSION: AA administration could attenuate a number of deleterious reactions after traumatic SCI. Further studies are needed to elucidate the pathways of neuroprotective effects of AA after spinal trauma.

Comparative Biochemical and Motor Function Analysis of Alpha Lipoic Acid and N-Acetyl Cysteine Treatment on Rats with Experimental Spinal Cord Injury.

AIM: Spinal Cord Injury (SCI) is a devastating health problem both for the patient and the clinician. Numerous treatment modalities have been studied to reverse the effects of spinal cord injury. Herein is reported the effects and the comparison of Alpha Lipoic Acid and N-Acetyl Cysteine on rats with SCI. MATERIAL AND METHODS: 38 adult male Sprague-Dawley rats were randomly divided into 5 groups: only laminectomy, laminectomy and trauma, laminectomy trauma and Alpha Lipoic Acid 100 mg/kg IP administration, laminectomy trauma and N-Acetyl Cysteine 300 mg/kg IP administration, and vehicle group (PEG). The trauma model was the Modified Allen Weight drop method. After the procedure, the rats' motor function was evaluated using the modified Tarlov Scale and consequently they were sacrificed and the spinal cord tissue was analyzed biochemically for inflammation markers. RESULTS: Both Alpha Lipoic Acid and N-Acetyl Cysteine administration after the injury significantly improved the results. There was no statistically significant difference in between the agents. CONCLUSION: Although these agents both proven to be effective in ameliorating the effects of SCI, there was not enough evidence in this research to conclude the benefit of one agent over the other.

Trigeminal Neuralgia as an Unusual Isolated Symptom of Pituitary Adenoma: Case Report and Review of the Literature.

Pituitary adenomas account for approximately 10% of intracranial tumors and 5% are locally invasive. Cavernous sinus invasion by pituitary tumors presents mostly with cranial nerve palsies, especially involving the third, fourth and sixth cranial nerves, which is well documented in the literature. However, an isolated complaint of trigeminal neuralgia due to pituitary adenoma is an extremely rare entity with a limited number of reported cases. A 51-year-old female patient presented to our clinic with complaints of pain and numbness on the left side of face for six months, with each event lasting 5-10 seconds. No improvement was obtained with administration of carbamazepine therapy. Magnetic resonance imaging of the sellar region revealed a mass with the left cavernous sinus invasion. The patient underwent surgery via endoscopic transsphenoidal approach and after than radiosurgery with gamma-knife. The patient's complaints resolved totally after gamma-knife radiosurgery. We report herein a case of pituitary adenoma with an isolated complaint of trigeminal neuralgia. Pituitary adenomas may be presented with cavernous sinus invasion and multiple cranial nerve palsies but isolated trigeminal neuralgia due to pituitary adenoma is an extremely rare entity.

Six-level isolated spinous process fracture of the thoracic vertebrae (clay-shoveler's fracture) and a review of the literature.

Clay-shoveler's fractures are isolated, avulsion-type spinous process fractures of the lower cervical and upper thoracic vertebrae. Multi-level fractures of the spinous processes are extremely rare. We report the case of a 60-year-old female patient with a six-level isolated spinous process fracture of the thoracic spine. Our case is the fourth reported case in literature, of an isolated spinous process fracture involving five or more levels in the thoracic vertebrae.

Effects of tadalafil-Type-V phosphodiesterase enzyme inhibitor-On rats with spinal trauma.

In this research, the effect of tadalafil, a selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, on rats with spinal trauma was evaluated. The evaluation consisted of neurological examination and biochemical parameters. Twenty healthy male Wistar albino rats were used in this study. They were separated into three groups: tadalafil-receiving (TD) group (n=7), laminectomy and trauma (LT) group (n=7), and just laminectomy group (n=6). The TD group received daily dose of tadalafil (10 mg/kg) for a week along with bait and water. Each rat's spinal cord was dissected with utter caution. The spinal cord was traumatized by Allen's weight-drop method. Using a standard apparatus, 5 g of weight was dropped from a height of 10 cm on the spinal cords of the TD and LT (laminectomy+trauma) group. No extra maneuvers were conducted on the laminectomy group. A day later, the rat's functional neurological status was examined followed by re-exploration of the spinal cord for sampling 1 cm of tissue. The Tarlov scale was used to evaluate the functional neurological status. The modified Tarlov scale was rated to be significantly higher in the TD group than that in the LT group. For the biochemical parameters, malondialdehyde (MDA) and cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) involved in the inflammatory process were examined. MDA--an indicator of lipid peroxidation--was found to be significantly lower in the TD group compared with that in the LT group. TNF-α and IL-6 levels were also found to be lower in the TD group compared with those in the LT group. Shortly, this research showed that the use of TD group in spinal trauma resulted in better neurological outcome and significant improvement in biochemical parameters.

Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury.

There is an urgent need to develop new therapeutic approaches for the treatment of severe neurological trauma, such as stroke and spinal cord injuries. However, many drugs with potential neuropharmacological activity, such as adenosine, are inefficient upon systemic administration because of their fast metabolization and rapid clearance from the bloodstream. Here, we show that conjugation of adenosine to the lipid squalene and the subsequent formation of nanoassemblies allows prolonged circulation of this nucleoside, providing neuroprotection in mouse stroke and rat spinal cord injury models. The animals receiving systemic administration of squalenoyl adenosine nanoassemblies showed a significant improvement of their neurologic deficit score in the case of cerebral ischaemia, and an early motor recovery of the hindlimbs in the case of spinal cord injury. Moreover, in vitro and in vivo studies demonstrated that the nanoassemblies were able to extend adenosine circulation and its interaction with the neurovascular unit. This Article shows, for the first time, that a hydrophilic and rapidly metabolized molecule such as adenosine may become pharmacologically efficient owing to a single conjugation with the lipid squalene.

Systemic administration of atorvastatin improves locomotor functions and hyperacute-acute response after experimental spinal cord injury: an ultrastructural and biochemical analysis.

AIM: Spinal cord injury (SCI) is characterized by posttraumatic inflammatory cascades including excitotoxicity, oxidative stress, and apoptosis. Agents against neuroinflammation are the current scope of studies on experimental SCI with promising results. MATERIAL AND METHODS: Thirty-two male Sprague-Dawley rats weighing 250-320 gram were used. They were randomized and divided into four groups with eight animals in each as sham, control, SCI+PEG (polyethylene glycol) and SCI+atorvastatin group. Rats were anesthetized with intraperitoneal ketamine (80 mg/kg) and xylazine (10 mg/kg) and SCI was induced by the weight-drop model. A single level laminectomy was performed at T10 and the spinal column was immobilized with a stereotactic device. Rats in the treatment group received ip atorvastatin at 0.2 mg/kg. Neurological impairments were examined through Modified Tarlov's and inclined angle scores. The SCI section was resected for electron-microscopic analysis, IL-1ß and IL-6 level. All data were analyzed using one-way ANOVA and Dunnet T3 test. RESULTS: Atorvastatin improved locomotor recovery after rat SCI. The results were further confirmed with a statistically significant decrease of IL-1ß, IL-6 and lipid peroxide levels. This finding revealed the anti-inflammatory and beneficial effect of atorvastatin on rat SCI. CONCLUSION: The present study focused on both B and T cell mediated immunity and confirmed the beneficial effect of atorvastatin with decreased expressions of IL-1ß and IL-6.

A quadruped study on chitosan microspheres containing atorvastatin calcium: preparation, characterization, quantification and in-vivo application.

Atorvastatin is commonly used as a cholesterol lowering agent in patients. Recently, the neuroprotective effects of atorvastatin became the focus of many research studies. In this study, we have formulated chitosan microspheres containing atorvastatin calcium. In-vitro characterization of chitosan microspheres and quantification of atorvastatin calcium from formulations were also evaluated. The neuroprotective efficiency of atorvastatin calcium was investigated by an experimental spinal cord injury model. Atorvastatin calcium microspheres were implanted at the laminectomy area (1 mg/kg) immediately after trauma. Twenty-four hours after injury, motor functions of animals were scored according to modified Tarlov Scale. In spinal cord tissues tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and lipid peroxidation levels were quantified and ultrastructural changes have been investigated. The results of all parameters indicate that microspheres containing atorvastatin calcium were capable of improving functional outcome, attenuating the expression of TNF-alpha, IL-1beta and IL-6; lowering lipid peroxidation levels and maintaining the preservation of the cellular uniformity.

Local administration of chitosan microspheres after traumatic brain injury in rats: a new challenge for cyclosporine--a delivery.

The major aim of this study was to evaluate the efficiency of chitosan microspheres containing cyclosporine-A (Cs-A) on mitochondrial damage in traumatic brain injury (TBI) animal model. Trauma was introduced to male Sprague-Dawley (SD) rats similar to that of modified Feeney Method. Briefly, after craniectomy in the left parietal region (5 mm). Trauma was performed by dropping 24 g metal sterile rods through a teflon guide tube (9.3 cm) on a foot plate placed over the duramater. Just after the trauma, 20 mg/kg Cs-A (Sandimmune) has been administered to the traumatised SD rats intraperitoneally (i.p.). On the other hand, only chitosan microspheres containing 10 mg/kg was implanted at the craniectomy area locally after trauma in Group E. A small piece of surgicell was placed over the craniectomy hole and the scalp incision was sutured. 24 h after injury and the brain tissues were removed intact. The results were evaluated through lipid peroxidation ratio and ultrastructural grading system. The statistical comparisons were evaluated by using Mann Whitney- U test at the significance level p = 0.05. The lipid peroxidation ratios of sham (78.4 +/- 6.0 nmol/g tissue) and vehicle (80.2 +/- 10.6 nmol/g tissue) were significantly increased 24 h after TBI. However, for treatment groups (i.p. Cs-A; 20 mg/kg) and (10 mg/kg Cs-A in microspheres), statistically significant lower lipid peroxidation ratios were determined as 53.5 +/- 9.7 and 47.9 +/- 8.1 nmol/g tissue, respectively (p < 0.05). The mitochondrial damage scores of the treatment groups were recorded as 21.7 +/-2.6 and 19.4 +/- 3.9 for Group D and Group E, respectively. Both of these scores of the treatment groups were found as significantly different from the sham and vehicle groups' scores individually. The implantation of microsphere formulation has provided a better efficiency in keeping the uniformity of mitochondrial structure in this complex cascade of events after TBI.

Huge intradiploic epidermoid cyst.

A 60-year-old man presented with an occipital mass under the scalp and complained of headache, nausea, and dizziness. Magnetic resonance imaging showed a well-defined mass in the occipital scalp extending from the scalp through the cranium and several centimetres into the posterior fossa. There were well-defined margins in the deep portion and the mass was totally removed. Histological examination showed that the cystic structure was lined by squamous epithelium containing laminated keratin material. The pathological findings were consistent with the diagnosis of an epidermoid cyst. The patient was discharged free of symptoms.