Search

TBI is the main cause of death and disability in individuals aged 1–45 in Western countries. One of the main challenges of TBI at present is the lack of specific diagnostic biomarkers, especially for mild TBI (mTBI), which remains currently difficult to value in clinical practice. In this context MiRNAs may be important mediators of the profound molecular and cellular changes that occur after TBI in both the short and the long term. Recently, plasma miRNAs profiling in human TBI, have revealed dynamic temporal regulation of miRNA expression within the cortex. Aim of this study was to select a specific miRNAs panel for mTBI, by focusing the research on the prognostic meaning of miRNAs in the hours following the trauma, in order to be able to use this MIRNAs as potential biomarkers useful for monitoring the follow up of mild TBI. Serum levels of 17 miRNAs were measured by RT-quantitative polymerase chain reaction (qPCR) in 20 patients with mTBI at three different time-points (0h, 24h, 48h) and in 10 controls. For 15 miRNAs we found a significant differences in the comparison among the three time points: for each of these miRNAs the values were greater at baseline and progressively reduced at 24h and 48h. These data allow us to consider the miRNAs included in panel as sensitive and specific biomarkers for mTBI, useful in monitoring the post-trauma period.

Reactive oxygen species (ROS) represent reactive products belonging to the partial reduction of oxygen. It has been reported that ROS are involved in different signaling pathways to control cellular stability. Under normal conditions, the correct function of redox systems leads to the prevention of cell oxidative damage. When ROS exceed the antioxidant defense system, cellular stress occurs. The cellular redox impairment is strictly related to tumorigenesis. Tumor cells, through the generation of hydrogen peroxide, tend to the alteration of cell cycle phases and, finally to cancer progression. In adults, the most common form of primary malignant brain tumors is represented by gliomas. The gliomagenesis is characterized by numerous molecular processes all characterized by an altered production of growth factor receptors. The difficulty to treat brain cancer depends on several biological mechanisms such as failure of drug delivery through the blood-brain barrier, tumor response to chemotherapy, and intrinsic resistance of tumor cells. Understanding the mechanisms of ROS action could allow the formulation of new therapeutic protocols to treat brain gliomas.

OBJECTIVE Total brain water content changes in several cerebral pathological conditions and the measurement of brain water content are important for the selection of appropriate therapeutic procedures. We present a quantitative, in vivo, bioelectrical impedance analysis (BIA) method and propose its use for the accurate assessment of brain water content among human subjects. METHODS Cerebral BIA is based on the conduction of an applied current in the brain parenchyma. Application of an excitatory current of 800 microA at 50 kHz, via two electrodes placed on the eyelids with the eyes closed, and detection of the voltage drop with two electrodes placed in the suboccipital region allow brain resistance and reactance to be measured. By means of an equation that considers cranial circumference and resistance, it is possible to quantify the total brain water content, expressed as the bioelectrical volume. Cerebral BIA was performed with a series of healthy volunteers (n = 100), for determination of average brain water content values. The method was then applied to 50 patients with brain tumors (n = 20), intracranial hemorrhage (n = 16), or hydrocephalus (n = 14), for assessment of changes in global brain water contents. Data were compared with those obtained for healthy volunteers. RESULTS Statistically significant differences (P < 0.001) were observed between the two groups. Mean brain water content values (expressed as bioelectrical volume values) were 38.2 +/- 3.9 cm2/Omega for healthy volunteers and 67.7 +/- 13.1 cm2/Omega for patients with cerebral pathological conditions. Statistically significant differences (P < 0.05) were also observed among patients with cerebral pathological conditions. CONCLUSION The results of this study suggest that BIA, applied to the cerebral parenchyma, is a valid method for the prediction of brain water contents under both normal and pathological conditions. However, further studies are needed to establish whether it is sensitive and reliable enough for future clinical applications.

Cerebral vasospasm and ischemic damage are important causes of mortality and morbidity in patients affected by aneurysmal subarachnoid hemorrhage (SAH). Recently, i.p. administration of recombinant human erythropoietin (r-Hu-EPO) has been shown to exert a neuroprotective effect during experimental SAH. The present study was conducted to evaluate further the effect of r-Hu-EPO administration after SAH in rabbits on neurological outcome, degree of basilar artery spasm, and magnitude of neuronal ischemic damage. Experimental animals were divided into six groups: group 1 ( n = 8), control; group 2 ( n = 8), control plus placebo; group 3 ( n = 8), control plus r-Hu-EPO; group 4 ( n = 8), SAH; group 5 ( n = 8), SAH plus placebo; group 6 ( n = 8), SAH plus r-Hu-EPO. r-Hu-EPO, at a dose of 1,000 units/kg, and placebo were injected i.p. starting 5 min after inducing SAH and followed by clinical and pathological assessment 72 h later. Systemic administration of r-Hu-EPO produced significant increases in cerebrospinal fluid EPO concentrations ( P < 0.001), and reduced vasoconstriction of the basilar artery ( P < 0.05), ischemic neuronal damage ( P < 0.001), and subsequent neurological deterioration ( P < 0.05). These observations suggest that r-Hu-EPO may provide an effective treatment to reduce the post-SAH morbidity.

Aim Trigeminal neuralgia is a disabling form of facial pain that causes a considerable discomfort and a marked reduction in the quality of life. Although neurovascular compression is often associated with trigeminal neuralgia, other intracranial pathologies can result in compression along the nerve. Case description The authors report a case of a patient suffering from a typical left trigeminal neuralgia affecting both the second and the third branches. Neuroradiological examinations showed the presence of an arachnoid cyst located in the left temporal lobe, contiguous with the Meckel's cave, eroding the greater wing of the sphenoid bone. Following a meticulous decision-making process the patient underwent conservative treatment with success. A properly modulation of the drug dosage allowed pain relief to be achieved. Conclusion This is a rare case reporting a typical trigeminal neuralgia by an arachnoid cyst of the Meckel's cave mimicking a neurovascular compression syndrome. Our findings, behind the review of the current literature, point out the importance of such a pathological condition when dealing with patients affected by cranial nerve dysfunction syndrome.

This is the first case of multiple (triple) pituitary micro-adenomas documented by magnetic resonance imaging (MRI) in a living patient and treated by a transsphenoidal microsurgical approach. The patient, a 37-year-old woman, complained of a long history of bifrontal headache, weight gain and oligomenorrhea. Physical examination revealed moderate hirsutism and a slight fat pad overlying the vertebrae. Routine laboratory studies and endocrinological biochemical investigations were normal. A gadolinium-enhanced MRI of the pituitary region revealed three intrapituitary micro-adenomas. A transsphenoidal microsurgical approach to the pituitary gland was carried out and micro-adenomas were completely removed one at a time. One year follow-up showed complete resolution of clinical symptoms and signs and normal biochemical parameters of pituitary function.

Patients affected by cerebral gliomas, despite classical strategies adopted, show a very poor prognosis. Current treatment consists of regimens that include surgical debulking, radiation therapy, and systemic chemotherapy. However, the median survival after surgery and radiation therapy alone is 9 months, and systemic chemotherapy is minimally effective. Advances in molecular biology have better depicted the mechanisms involved in the genesis of cerebral gliomas and identified specific gene sequences to be targeted in the malignant cell genome. Gene expression can be blocked using various strategies. The concept of antisense-mediated gene inhibition has now emerged as a potentially powerful alternative or adjunct to conventional cancer chemotherapy. This strategy is able to block selectively glioma cells which interfer to gliomagenesis molecular pathways. The antisense molecules, delivered inside the brain, penetrate into glioma cells blocking specific genic functions. Antisense oligonucleotides are complementary to the target mRNA and this bind cause the block and/or the reduction of the encoded protein synthesis. Genes coding for growth factors and their receptors, proto-oncogenes, cellular proteases, kinases, and proteins important in cell cycle control and apoptosis represent ideal target for antisense oligonucleotides treatment. In this study, we report the most relevant findings of antisense oligonucleotides application in gliomas treatment.

Non-traumatic intradiploic arachnoid cyst is a rare condition. We describe a young man with typical trigeminal neuralgia and intradiploic arachnoid cyst at the greater wing of the sphenoid. The patient was successfully treated with medical therapy. To our knowledge, this is the first case report of a possible correlation between trigeminal neuralgia and intraosseous arachnoid cyst. We describe the clinical case, the possible pathogenetic mechanism and briefly review the literature.

OBJECTIVE: Intracerebral hemorrhage (ICH) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, erythropoietin (EPO) and its long-lasting analog, darbepoetin alfa, have been demonstrated to be neuroprotective in several models of neuronal insult. The objectives of this study were to analyze whether the systemic administration of recombinant human EPO (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery and brain damage in a rat model of ICH. METHODS: Experimental ICH was induced in rats by injecting autologous blood into the right striatum under stereotactic guidance. Subsequently, animals underwent placebo treatment, daily injections of rHuEPO, or weekly injections of darbepoetin alfa. Animals were killed 14 days after injury. RESULTS: Both rHuEPO and darbepoetin alfa were effective in reducing neurological impairment after injury, as assessed by the neurological tasks performed. rHuEPO- and darbepoetin alfa-treated animals exhibited a restricted brain injury with nearly normal parenchymal architecture. In contrast, the saline-treated group exhibited extensive cerebral cytoarchitectural disruption and edema. The number of surviving NeuN-positive neurons was significantly higher in the rats treated with rHuEPO and darbepoetin alfa compared with those that received saline (P < 0.05). CONCLUSION: These results demonstrate that weekly administered darbepoetin alfa confers behavioral and histological neuroprotection after ICH in rats similar to that of daily EPO administration. Administration of EPO and its long-lasting recombinant forms affords significant neuroprotection in an ICH model and may hold promise for future clinical applications.

Introduction Metastases are the most frequent malignant lesions of the spine. Around 5 to 10% of the patients with a systemic tumor have got spinal metastases. More than 95% of spinal metastases are extradural lesions. The residual cases are intradural extramedullary lesions and only 0.5% are intramedullary lesions. Prostate, lung, breast, clear cell kidney tumors, lymphoma, myeloma, and gastric carcinoma are the most frequent primitive neoplasms to cause secondary lesions to the spine. The cervical spine is involved in 10% of the cases. In 80% of the cases, metastases are found to be in the lower cervical tract. Life expectancy in patients with lung carcinoma metastasis is approximately 6 months, 1.5/2 years in patients affected by breast, kidney, and prostate cancers. We reviewed our series of patients with spinal metastases operated between 1997 and 2013 with the aim to analyze the efficacy of the surgical treatment to recover the function and biomechanics of the vertebral column. We evaluated the prognosis in terms of duration and quality of residual life. Materials and Methods We included 36 patients (mean age 65 years). The patients were evaluated according to neurological status, Karnofsky score for the quality of life, and Denis score for pain. Indications for surgery were: pain resistant to pharmacological therapy, medullary compression, neurological deficits, and vertebral instability. Patients underwent CT and MR scan examinations of the cervical spine. In all patients, a total body CT scan was performed. All surgical procedures were performed with microsurgical techniques. In 25 cases, the surgical treatment contemplated an anterior approach: single corpectomy in 16 cases and double in 11 cases. In these cases, the vertebral body was replaced by an expandable titanium cage with PMMA filling and plating. In 6 cases, the treatment consisted of a 360-degree reconstruction. In the residual 5 cases, where the lesion was located in the superior cervical tract of the spine, we performed an occipital–cervical fusion through a posterior approach. Postoperative follow-up controls were run at 1, 3, 6, and 12 months. A cervical orthosis was worn by the patient for 40 days. Results During the follow-up time, 18 patients died because of the progression of the primitive tumor. In 36 patients treated with surgery, the histological examination documented a primitive lesion of the breast in 12 cases, of the lung in 10 cases, of the prostate in 5, of the kidney in 4, of the thyroid in 2, and of the testicle in 2. One patient affected by plasmacytoma was also observed. No intra- and perioperative complications arose. The neurological status was preserved intact in all cases with a sensible improvement in those patients affected by severe tetraparesis. We noticed a rise in the Karnofsky score, on an average from 70 to 85. Postoperative neuroimaging controls documented that the instrumentation was in the correct place. Conclusion Surgical treatment of spine metastases allows pain control, management of neurological conditions, and an overall improvement in the quality of residual life.

Object Spinal cord injury (SCI) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, erythropoietin (EPO) and its nonerythropoietic derivatives asialoEPO and carbamylated EPO have markedly improved functional outcome when administered after compressive SCI. However, an optimum treatment paradigm is currently unknown. Because the uninjured spinal cord expresses a high density of EPO receptor (EPOR) in the basal state, signaling through these existing receptors in advance of injury (pharmacological preconditioning) might confer neuroprotection and therefore be potentially useful in situations of anticipated damage. Methods The authors compared asialoEPO, a molecule that binds to the EPOR with high affinity but with a brief serum half-life (t1/2 < 2 minutes), to EPO to determine whether a single dose (10 μg/kg of body weight) administered by intravenous injection 24 hours before 1 minute of spinal cord compression provides benefit as determined by a 6-week assessment of neurological outcome and by histopathological analysis. Rats pretreated with asialoEPO or EPO and then subjected to a compressive injury exhibited improved motor function over 42 days, compared with animals treated with saline solution. However, pretreatment efficacy was substantially poorer than efficacy of treatment initiated at the time of injury. Serum samples drawn immediately before compression confirmed that no detectable asialoEPO remained within the systemic circulation. Western blot and immunohistochemical analyses performed using uninjured spinal cord 24 hours after a dose of asialoEPO exhibited a marked increase in glial fibrillary acidic protein, suggesting a glial response to EPO administration. Conclusions These results demonstrate that EPO and its analog do not need to be present at the time of injury to provide tissue protection and that tissue protection is markedly effective when either agent is administered immediately after injury. Furthermore, the findings suggest that asialoEPO is a useful reagent with which to study the dynamics of EPO-mediated neuroprotection. In addition, the findings support the concept of using a nonerythropoietic EPO derivative to provide tissue protection without activating the undesirable effects of EPO.

OBJECTIVE: The purpose of this study was to better elucidate the anatomic relationship between the vertebral artery (VA) along with its perforating vessels and the brainstem to develop anatomic guidelines that would be helpful when decompressing medulla oblongata compressed by the VA. METHODS: Microanatomy dissection was performed in six formalin-fixed cadaveric heads. The VA, posteroinferior cerebellar artery (PICA), anteroinferior cerebellar artery (AICA), and lower brainstem perforators were examined under magnification using a surgical microscope. The outer diameters of the VA, PICA, and AICA were measured. The distance between the VA, lying within the lateral cerebellomedullary cistern, and the medulla oblongata was quantified. The lower brainstem perforating vessels were examined in relation to their course, outer diameter, and length. RESULTS: In four of six brains, the left VA was dominant, presenting an outer diameter at least 0.8 mm larger than the contralateral VA. The average distance between the VA and the medulla oblongata was 3 mm. The perforating branches presented a mean outer diameter of 0.7 mm. In particular, perforators arising from the VA and PICA (Groups 1 and 2) presented an average outer diameter of 0.2 mm and an average length of 7 mm. Perforating vessels arising from the AICA and vertebrobasilar junction (Groups 3 and 4) presented an average outer diameter of 0.4 mm and an average length of 12 mm. CONCLUSION: This work provides new information that may be useful to minimize the risk of injury of perforators when operating on medulla oblongata compression by the VA.

Erythropoietin exerts a neuroprotective effect during cerebral ischemia. We investigated the effect of systemic administration of recombinant human erythropoietin in a rabbit model of subarachnoid hemorrhage-induced acute cerebral ischemia. The animals were divided into three groups: group 1, subarachnoid hemorrhage; group 2, subarachnoid hemorrhage plus placebo; group 3, subarachnoid hemorrhage plus recombinant human erythropoietin (each group, n=8). Experimental subarachnoid hemorrhage was produced by injecting autologous blood into the cisterna magna. Treatment with recombinant human erythropoietin and placebo was started 5 min after subarachnoid hemorrhage and was continued every 8 h for 24 h. Before the animals were killed, erythropoietin concentration was measured in the cerebrospinal fluid. The rabbits were killed 24 h after subarachnoid hemorrhage and ischemic brain injury was histologically evaluated. In group 3, the concentration of erythropoietin in the cerebrospinal fluid was significantly increased and a significant reduction in cortical necrotic neuron count was also observed. These findings may encourage the use of erythropoietin in the treatment of cerebral ischemia that often occurs in the early stage of subarachnoid hemorrhage.

Nervous system diseases are very complex conditions comprising a large variety of local and systemic responses. Several therapeutic agents interfering with all or in part the biochemical steps that ultimately cause neuronal death have been demonstrated to be neuroprotective in preclinical models. However, all the agents so far investigated have inexorably failed in the phase III trials carried out. A large body of evidence suggests that the hormone erythropoietin (EPO), besides its well-known hematopoietic action, exerts beneficial effects in the central nervous system. EPO's effect has been assessed in several experimental models of brain and spinal cord injury thus becoming a serious candidate for neuroprotection. The use of EPO as neuroprotectant raises several questions. Besides dosage and therapeutic time window, the safety of recombinant EPO administration in the setting of nervous system diseases takes priority over all other questions. Although recombinant EPO seems to be potentially safe at the neuroprotective proved doses, cardiovascular or cerebrovascular events can occur as a result of its bone marrow stimulating activities. The successful trial using EPO in patients with ischemic stroke and the large body of experimental evidence encourages intensive evaluation of this cytokine to support safe and larger clinical trials in the near future. © 2007 Prous Science. All rights reserved.

Object. Results of recent studies indicate that erythropoietin (EPO) produces a neuroprotective effect on experimental subarachnoid hemorrhage (SAH). It has been reported that S-100 protein levels increase in cerebrospinal fluid (CSF) after SAH, providing a highly prognostic indication of unfavorable outcome. This study was conducted to validate further the findings of S-100 protein as an index of brain damage and to assess whether treatment with recombinant human EPO (rhEPO) would limit the increase of S-100 protein level in CSF following experimental SAH. Methods. Thirty-two rabbits were each assigned to one of four groups: Group 1, control; Group 2, SAH; Group 3, SAH plus placebo; and Group 4, SAH plus rhEPO (each group consisted of eight rabbits). The rhEPO and placebo were administered to the rabbits after SAH had been induced, and S-100 protein levels in the CSF of these animals were measured at 24, 48, and 72 hours after the experimental procedure. In each group of animals levels of S-100 protein were compared with the mortality rate, neurological outcome, and neuronal ischemic damage. High S-100 protein levels were found in rabbits in Groups 2 and 3, which exhibited poor neurological status and harbored a high number of damaged cortical neurons. Favorable neurological outcome and significant reductions in total numbers of damaged neurons were observed in animals in Group 4 in which there were significantly lower S-100 protein concentrations compared with animals in Groups 2 and 3 (p < 0.001). Conclusions. The results of this study support the concept that determination of the S-100 protein level in CSF has prognostic value after SAH. The findings also confirm that rhEPO acts as a neuroprotective agent during experimental SAH.