The Effect of Human Mesenchymal Stem Cells Derived from Wharton's Jelly in Spinal Cord Injury Treatment Is Dose-Dependent and Can Be Facilitated by Repeated Application.

Human mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) were used for the treatment of the ischemic-compression model of spinal cord injury in rats. To assess the effectivity of the treatment, different dosages (0.5 or 1.5 million cells) and repeated applications were compared. Cells or saline were applied intrathecally by lumbar puncture for one week only, or in three consecutive weeks after injury. Rats were assessed for locomotor skills (BBB, rotarod, flat beam) for 9 weeks. Spinal cord tissue was morphometrically analyzed for axonal sprouting, sparing of gray and white matter and astrogliosis. Endogenous gene expression (Gfap, Casp3, Irf5, Cd86, Mrc1, Cd163) was studied with quantitative Real-time polymerase chain reaction (qRT PCR). Significant recovery of functional outcome was observed in all of the treated groups except for the single application of the lowest number of cells. Histochemical analyses revealed a gradually increasing effect of grafted cells, resulting in a significant increase in the number of GAP43+ fibers, a higher amount of spared gray matter and reduced astrogliosis. mRNA expression of macrophage markers and apoptosis was downregulated after the repeated application of 1.5 million cells. We conclude that the effect of hWJ-MSCs on spinal cord regeneration is dose-dependent and potentiated by repeated application.

A comparison of equivolume, equiosmolar solutions of hypertonic saline and mannitol for brain relaxation in patients undergoing elective intracranial tumor surgery: a randomized clinical trial.

BACKGROUND: Hyperosmolar solutions have been used in neurosurgery to modify brain bulk and prevent neurological deterioration. The purpose of the study was to compare the effects of equivolume, equiosmolar solutions of mannitol and hypertonic saline (HTS) on brain relaxation and postoperative complications in patients undergoing elective intracranial tumor surgery. METHODS: In this prospective, randomized study, patients with American Society of Anesthesiologists physical status I to III scheduled to undergo a craniotomy for intracranial tumors were enrolled. Patients received a 3.75 mL/kg intravenous infusion of either 3.2% HTS (group HTS, n=36) or 20% mannitol (group M, n=38). The surgeon assessed the condition of the brain using a 4-point scale after opening the dura. Recorded measures included duration of surgery, blood loss, urine output, volume and type of infused fluids, hemodynamic variables, electrolytes, glucose, creatinine, predefined postoperative complications, and length of intensive care unit and hospital stays. RESULTS: Brain relaxation conditions in group HTS (score 1/2/3/4, n=10/17/2/7) were better than those in group M (score 1/2/3/4, n=3/18/3/14, P=0.0281). Patients in group M had higher urine output, received more crystalloids during surgery, and displayed lower central venous pressure and lower natremia at the end of surgery than did patients in group HTS. No significant differences in postoperative complications or lengths of intensive care unit and hospital stays were observed between the groups. CONCLUSIONS: Our results suggest that HTS provides better brain relaxation than mannitol during elective intracranial tumor surgery.

NANOTECHNOLOGY - NEW TRENDS IN THE TREATMENT OF BRAIN TUMOURS.

High grade gliomas are some of the deadliest human tumours. Conventional treatments such as surgery, radiotherapy and chemotherapy have only a limited effect. Nowadays, resection is the common treatment of choice and although new approaches, such as perioperative magnetic resonance imaging or fluorescent microscopy have been developed, the survival rate of diagnosed patients is still very low. The inefficacy of conventional methods has led to the development of new strategies and the significant progress of nanotechnology in recent years. These platforms can be used either as novel imaging tools or to improve anticancer drug delivery into tumours while minimizing its distribution and toxicity in healthy tissues. Amongst the new nanotechnology platforms used for delivery into the brain tissue are: polymeric nanoparticles, liposomes, dendrimers, nanoshells, carbon nanotubes, superparamagnetic nanoparticles and nucleic acid based nanoparticles (DNA, RNA interference [RNAi] and antisense oligonucleotides [ASO]). These nanoparticles have been applied in the delivery of small molecular weight drugs as well as macromolecules - proteins, peptides and genes. The unique properties of these nanoparticles, such as surface charge, particle size, composition and ability to modify their surface with tissue recognition ligands and antibodies, improve their biodistribution and pharmacokinetics. All of the above mentioned characteristics make of nanoplatforms a very suitable tool for its use in targeted, personalized medicine, where they could possibly carry large doses of therapeutic agents specifically into malignant cells while avoiding healthy cells. This review poses new possibilities in the large field of nanotechnology with special interest in the treatment of high grade brain tumours.

Abnormalities of tau-protein and beta-amyloid in brain ventricle cerebrospinal fluid.

OBJECTIVE: Determination of various biomarkers, such as beta-amyloid, tau-protein, phosphorylated tau-protein in CSF and their sensitivity and specificity in neurodegenerative brain processes, in particular Alzheimer Dementia (AD), has been recently investigated to monitor their abnormalities in the CSF at early stages of diseases before the clinical manifestation. DESIGN AND SETTING: In the pilot group of our patients (10 men / 5 women) who underwent a drainage neurosurgical procedure for diagnosis of hydrocephalus, CSF was obtained from the brain ventricles and the influence of a different compartment of the CSF on the level of biomarkers, tau-protein and beta-amyloid, was investigated. RESULTS: The mean tau-protein level for all 15 patients was 812.0 pg/ml, with median value 363.7 pg/ml; while mean beta-amyloid level for all 15 patients was 526.7 pg/ml, with median value 239.5 pg/ml, respectively. The abnormal tau-protein and beta-amyloid levels were found in the subgroup of patients in whom hydrocephalus was caused by a severe pathological process, such as brain tumor. The beta-amyloid values were significantly lower also in comparison with our previously published results in patients with AD in the CSF obtained by lumbar puncture in the spinal canal. CONCLUSIONS: CSF in the brain ventricles is theoretically more stable and the values in this CSF probably provide more reliable informations for clinical diagnostic procedure than those for the CSF obtained by lumbar puncture in the spinal canal.

The potential benefit of intracarpal pressure measurement in endoscopic carpal tunnel syndrome surgery--an analysis of EMG findings and pressure values.

Endoscopic carpal tunnel syndrome surgery is a modern minimally invasive method of carpal tunnel decompression. However, the method does also have its critics, who emphasize that there is an increased rate of complications in comparison to open procedures. To further improve and optimize results of endoscopic surgery we used an intracarpal pressure sensor to verify the effect of carpal tunnel decompression. The endoscopic single portal approach was used in all cases. Median nerve conduction studies were performed prior to and 3 months after surgery. Two groups, those with pressure studies and those without, were then compared according to several EMG parameters such as: median nerve distal motor latency, amplitude of motor response, sensory nerve conduction velocity to the index finger, and amplitude of sensory nerve action potential. In both groups, we observed similarly significant improvements in all conduction parameters, except the amplitude of motor response, which did not change in either group, i.e. no difference in postoperative EMG between the two groups was observed. Despite this fact, intracarpal pressure measurement is still useful in localising the point in which the median nerve is compressed and provides valuable functional information on the level decompression achieved.

[Surgical treatment of brain abscess--retrospective analysis of the group of patients with brain abscess, treated at our department in last 12 years]. / Chirurgická lécba abscesu mozku--retrospektivní analýza souboru nemocných s diagnózou abscesu mozku, lécených na nasem pracovisti za posledních 12 let.

The authors retrospectively evaluated group of patiens treated at the Department of neurosurgery in Hradec Králové from 10/1993 to 10/2004 with the diagnosis of brain abscess. During this period, we treated 23 patients, 15 males and 8 women with the median age 48 years. Patiens with the iatrogenic etiology and those with pyocefalus and subdural and epidural empyema were excluded from this group. We provided 45 surgical procedures with total mortality 17,4 %.

[Indication and radicality of surgical treatment in spinal myeloma]. / Indikace a radikalita chirurgické lécby myelomu v páteri.

In our set of 19 operated patients with spinal myeloma it was in 17 patients (89%) the first manifestation of malignant haematological disease. Indication for admission for surgery were in 18 patients (92%) graphical signs of spinal compression of osteolytic affliction of the vertebra of unclear aetiology, which in 17 (63%) of patients were demonstrated by neurological deficit. On the basis of graphical examinations the most frequent suspicion was on metastatic affliction of the spine at unknown primary focus and the basic diagnosis was determined after the operation at most of cases. In decision about the choice of radicalness of surgery intervention important data about the type of tumour in the spine were usually missing and it especially did not make possible to estimate the life expectation of the patient. When deciding about the radicalness of the surgery, we started from the degree of spinal compression and surgical character of pathological process in the spine. The aim of the operation is to decompress the spinal cord in tumour and to stabilize the afflicted part of the spine. Radical extirpation of tumour followed with stabilization and spine reconstruction we decided to carry out in 7 patients, i.e. 37%, all of them clinically improved and from this group only 2 patients (29%) died till now. We carried out only palliative surgery on the spine in next 12 patients, i.e. in 63%, only 6 patients improved neurologically, i.e. 50% and 10 patients, i.e. 83% died till now.