[The effect of gene therapy with the APOE3 Gene on structural and functional manifestations of secondary hippocampal damages in experimental traumatic brain injury].

AIM OF THE STUDY: to study the efficiency of gene therapy following traumatic brain injury (TBI) by evaluating the influences of liposomal transfection of the brain tissue by APOE3-containing plasmid vector on the structural and functional manifestations of development of secondary brain injuries after acute experimental TBI in the rats of different age. MATERIAL AND METHODS: Severe diffuse TBI in rats was inflicted under overall anesthesia by free load weighing 450 g, falling from a 1.5 m elevation. The mixture of DOTAP liposome and 25 µg of plasmid vector pCMV·SPORT6 with cDNA of APOE3 gene was infused intraventricularly using ALZET osmotic pumps. Combined morphological, electron microscopic, immunohistochemical and morphometric studies of СА1 hippocampal region were conducted in rats at days 5 and 10 following TBI and gene therapy after investigation of motor functions (using composite neurological motor score) and cognitive functions in Morris water maze. RESULTS: Significant changes in the morphofunctional state of hippocampus, as well as in the neurological and cognitive functions were shown on the model of severe TBI in the adult and old Wistar rats. Gene therapy, specifically cationic-liposome mediated APOE3 gene transfer to the CNS cells by plasmid vector, decreased a TBI-induced death of neurons and improved qualitative composition of neuronal population, normalized neuron-glial relations, decreased gliosis and microglial activation, axonal damage, myelin destruction and lipofuscin accumulation, all these having age-related peculiarities. After gene therapy observed in the animal brain was a lower intensity of the processes of apoptosis and a decrease of its rate in old animals. The above changes were accompanied with a more fast and expressed regress of neurological and cognitive disturbances typical for TBI. Administration of plasmid vector after TBI resulted in an increase of survival rate of old animals vs. old animals which got no gene therapy. CONCLUSION: APOE3 gene therapy has therapeutic potential in the treatment of severe TBI.

[Differentiated treatment of acute diffuse brain injuries].

Diagnosis and treatment results of 57 patients with acute diffuse brain injury have been analyzed. Patients were divided into two groups: first study period 2000-2005; second study period 2006-2010. The main differences between the first and the second study periods were in health condition and brain functions monitoring parameters, therapy approaches and goals. Increasing of axial and lateral dislocation symptoms during progression from the first type of diffuse injury to the fourth one is related to intracranial hypertension (ICH) occurrence rate and significance it's significance. During the second study period, ICH was found in 25% patients with the second type of injury, 57% patients with the third type of injury, and 80%, with the fourth type of injury. Mean ICP in the group of patients with the second type of diffuse injury comprised 14.4 +/- 6.6 mmHg; with the third type of injury, 30 +/- 20.6 mmHg; with the fourth type of injuty, 37.6 +/- 14.1 mmHg. Introduction of differentiated approach to conservative or surgical treatment method application to acute diffuse brain injuries patients based on ICP monitoring data led to 13.8% reduction in mortality in the second study period compared with the first study period.

[Peculiarities of the microsurgical discectomy for hernia of the low-lumbar vertebral column].

There were analyzed the results of observation in 642 patients with hernia of low-lumbar vertebral column, who were examined and operated on using microdiscectomy in the Department of endoscopic and laser spinal neurosurgery of Institute of Neurosurgery of Academy of Medical Sciences of Ukraine. There were delineated the indications for the methods of treatment, their efficacy was estimated, the immediate and late follow-up results of treatment were studied up. In one year after the medial hernia correction the persistent elimination of radicular compression syndrome was achieved in 86.5% of observations, after paramedian one--in 88.7% and postero-lateral--in 95.7%.

[Puncture vertebroplasty in aggressive hemangiomas of the vertebrae bodies]. / Punktsionnaia vertebroplastika pri agressivnykh gemangiomakh tel pozvonkov.

The paper presents the results of treatment in 15 patients with aggressive hemangiomas of the vertebral bodies, operated on by puncture vertebroplasty. The authors analyze current approaches to treating patients with this pathology, present criteria for aggressiveness of hemangiomas. The results of the treatment indicate that puncture vertebroplasty is highly effective and safe in treating patients with hemangiomas of the vertebral bodies.

[Percutaneous lumbar endoscopic diskectomy in discogenic lumbosacral radiculitis]. / Endoskopicheskaia portal'naia nukleoéktomiia pri diskogennykh poiasnichno-kresttsovykh radikulitakh.

The paper presents the results of percutaneous lumbar endoscopic diskectomy in 96 patients with discogenic lumbosacral radiculitis. Indications, contraindications, and surgical techniques are discussed. The intervention is shown to be highly effective (91.1%) in young patients with a relatively short history of the disease and hernias measuring as large as 8 mm. The paper analyzes complications and poor results of treatment using percutaneous lumbar endoscopic diskectomy.

[Endoscopic microsurgery in cervical disc hernias]. / Endoskopicheskaia mikrokhirurgiia pri gryzhakh sheinykh diskov.

The paper provides outcomes of treatment in 37 patients with cervical diskal hernias, operated on by endoscopic portal microsurgery. Surgery involved the use of video endoscopic techniques, microsurgery under fluoroscopic control. The duration of an operation was 22 +/- 2.7 min. Hospital stay was not more than 24 hours. Fair early and late outcomes were noted in 94.1% of the patients.

[Prospects of use of gene therapy in head trauma]. / Perspektivy ispol'zovaniia gennoi terapii pri cherepno-mozgovoi travme.

Neuronal injury may have one of the following three sequelae: death of the neurone, persistent atrophy or recovery. The ability of mature neurones to recover is dependent to a not inconsiderable degree on neurotrophins, on the basis of which consideration the following objective of genotherapy in craniocerebral injury (CCI) is formulated: achievement of therapeutically useful levels of expression of neutrophins by employment of genetical methodological approaches. The next prerequisite for institution of genotherapy in CCI is a proved dependance of CCI sequelae on individual genetic features, on APO E-genotype in particular, which fact suggests to us that specific correction is within the bounds of possibility. Another precondition for use of genotherapy in CCI is considered to be higher permeability of the blood-brain barrier in trauma, which even can facilitate the delivery of transgenes into the brain with the aid of those vectors the access of which to the central nervous system is limited under other conditions.

[Percutaneous laser diskectomy in cervical osteochondrosis]. / Punktsionnaia lazernaia diskéktomiia pri sheinom osteokhondroze.

The paper presents early and late outcomes of treatment in 62 patients undergone paracentetic laser "diskectomy" for discogenic compressed syndromes of the neck. It shows the efficiency of surgery for radicular (92.9%) and myelopathic (92.8%) syndromes. Patients were selected for these interventions on the basis of clinical and neurological examinations, spondylography, MRI, and electric neuromyography. The main stages of an operation were as follows: local anesthesia, right-sided anterolateral access, X-ray guidance of the position of a needle, one-stage removal of herniated disks during multi-levelled injury during an intervention. The operation lasted 18 +/- 2.4 minutes. The mean hospital stay was 12 +/- 1.4 hours. The interventions were performed in 16 of 62 cases in the outpatient setting.

[Application of the puncture laser diskectomy in the treatment of multiple hernias of sacro-iliac intervertebral disks]. / Primenenie punktsionnoi lazernoi diskektomii pri lechenii mnozhestvennykh gryzh mezhpozvonochnykh diskov poiasnichno-kresttsovogo otdela pozvonochnogo stolba.

In 144 patients with discogenic lumbosacralic radiculitis the puncture laser discectomy was performed on several levels independently or in combination with open operative intervention. High efficacy of treatment was noted.

[Individual selection of the total dose of laser energy in percutaneous laser disk nucleotomy]. / Individual'nyi vybor summarnoi dozy lazernoi énergii pri punktsionnoi lazernoi nukleotomii.

On the basis of studies on concentration and mobility of ions in the solution (conductometry technique) an individual selection is suggested of the total dose of laser energy during the percutaneous laser disk nucleotimy sessions. The conductometry technique permits arriving at an objective decision on both completion/continuation of the operation and change in the laser energy rate.

[The clinico-laboratory criteria of brain death in neurosurgical patients]. / Kliniko-laboratornye kriterii smerti mozga u neirokhirurgicheskikh bol'nykh.

With the purpose of developing scientifically substantiated criteria for brain death complex of clinical and physiological, biochemical, physicochemical, and morphological studies was initiated in 55 patients in a critical state because of a dangerous craniocerebral injury, tumours, and vascular affections of the brain. Generalized in the paper are well-known parameters characterizing irreversibility of changes. The following items are to be regarded as the principal criteria for brain death at the present stage of development of medicine: death of truncus cerebri and irreversibility of metabolic disturbances in brain activity.

[Free-radical perodixative reactions in the acute period of craniocerebral trauma]. / Svobodnoradikal'nye perekisno-okislitel'nye reaktsii v ostrom periode cherepno-mozgovoi travme.

The condition is analyzed of the pro-oxidant-antioxidant balance in patients in the acute phase of craniocerebral injury. The higher the degree of craniocerebral injury, the more enhanced are lipid peroxidation processes, the more apparent is the decline in the function of the bodily antioxidant system. Changes in metabolic processes were at their greatest in patients beyond forty four years of age, especially in women with severe craniocerebral injury. The authors recommend including natural and synthetic antioxidants into a complex of measures designed to treat craniocerebral injury.

[The activity of free-radical lipid-peroxidative reactions in the acute and late periods of severe craniocerebral trauma]. / Issledovanie aktivnosti svobodnoradikal'nykh perekisno-okislitel'nykh reaktsii v ostrom i otdalennom periode tiazheloi cherepno-mozgovoi travmy.

Severe craniocerebral injury is shown to result in intensification of processes of lipid peroxidation (LPO), decline in activity of the antioxidant system, which facts lead to further damage to the injured brain caused by products of LPO processes. Activity of LPO processes is recordable as is decline in activity of the antioxidant system after the treatment administered and in 12 and 24 months following the injury sustained as well. The authors recommend that natural and synthetic antioxidants be included into a complex of measures designed to treat severe craniocerebral injury.

[Radiation-induced intracranial meningiomas]. / Radioindutsirovannye vnutricherepnye meningiomy.

Based on the analysis of 112 cases a clinical characterization has been done of intracranial meningiomas developed secondary to X-ray irradiation of the head for fungus disease of skull integuments. X-ray irradiation increases the risk of intracranial meningioma development up to 4-fold. Radiation-induced intracranial meningiomas are characterized by particular features of clinical manifestations, by preponderance of hyperdense forms, by being of large size, as well as by a high frequency of changes in the adjacent bone presenting as hyperostosis, usuration, and destruction. The above meningiomas are notable for a high specific weight of anaplastic varieties.

[Laser puncture diskectomy in discogenic lumbosacral radiculitis]. / Punktsionnaia lazernaia diskéktomiia pri diskogennom poiasnichno-kresttsovom radikulite.

Percutaneous laser discectomy (PLD) was performed in 273 patients with herniated disc-induced lumbosacral radiculitis. Indications for PLD were based on clinical and neurological findings and results of MR tomography: no benefit from conservative treatment, pain syndrome in the lumbago stage and sciatica not presenting with severe paresis and with herniated intervertebral discs down to 6 mm in size across.

[Free-radical and neuroimmune processes in primary and repeated craniocerebral trauma (in an experiment)]. / Svobodnoradikal'nye i neiroimmunnye protsessy pri pervichnoi i povtornoi cherepno-mozgovoi travme (v éksperimente).

The impact of primary and repeated brain injury (BI) (moderate contusion of the brain) on changes of pro- and antioxidative processes in the brain and blood, as well as on the body's neuroimmune responses during 30 days following injury were studied in an experiment on albino rats. The changes in the rate of lipid peroxidation (LPO) were shown to be significantly higher in repeated BI than in primary one. There was no correlation between the changes in the rate of LPO in the blood and in the brain tissue. Immune disorders, namely: the proliferative activity of T and B lymphocytes were slightly milder than in primary BI while in repeated BI, neurosensitization was detectable earlier, which was more pronounced. Thus, goal-oriented correction of free radical processes should be made in the brain and of neuroimmune disorders in BI.

[The puncture laser dissectomy application for the discogenic lumbosacral radiculitis]. / Primenenie punktsionnoi lazernoi diskektomii po povodu diskogennogo poiasnichno-kresttsovoho radikulita.

The puncture laser discectomy was conducted in 273 patients with discogenic lumbosacral radiculitis while the conservative therapy inefficacy, pain syndrome in a lumbago stage present and lumboischialgia with absent prominent locomotive disorders and if the intervertebral disc hernia has the size up to 0.6 cm.

[Secondary craniocerebral trauma in acute disorders of the cerebral circulation]. / Vtorichnaia cherepno-mozgovaia travma pri ostrykh narusheniiakh mozgovogo krovoobrashcheniia.

As many as 69 records were reviewed of those patients predominantly in older age bracket, in whom acute cerebral circulatory disorder (hemorrhage in 26, infarction of the brain in 8, transient cerebral circulatory disturbances in 35) was a cause of their falling and incurring a craniocerebral injury. The studies made suggest that prior history, somatoneurological examination, information provided by various investigational modalities, especially computerized tomographic imaging, all might serve to make the diagnosis of associated brain injury more precise.

[The clinical manifestations of craniocerebral trauma in elderly patients]. / Klinicheskie proiavleniia cherepno-mozgovoi travmy u bol'nykh starcheskogo vozrasta.

It has been shown that over the recent 20 years the number of senile patients with a history of craniocerebral injury rose from 4.8 to 7.2% whereas in the group over 60, from 53 to 72%. In the course of "mild" craniocerebral injury, 21% of senile patients manifested secondary acute disorders of brain circulation that not infrequently eventuated in lethal outcomes. Of paramount importance in the clinical manifestation of craniocerebral injury in senile age is the growing deterioration of brain circulation rather than the rise of intracranial pressure.