[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%.

[Clinical characteristics of craniocerebral injury in patients with arterial hypertension]. / Klinicheskie osobennosti cherepno-mozgovoi travmy u bol'nykh s arterial'noi gipertenziei.

A comparative analysis of 408 cases of craniocerebral trauma (CCT) has revealed a considerable influence of hypertension on clinical manifestations of CCT. It has been found that in hypertensive patients the incidence of secondary acute impairments of the cerebral circulation predominantly of the ischemic type with less marked hypertensive and dislocation syndromes was 4-5 fold higher than in patients with normal blood pressure.

[Clinical characteristics of repeated cranio-cerebral injury]. / Klinicheskie osobennosti povtornoi cherepno-mozgovoi travmy.

The clinical manifestations of repeated craniocerebral injury indicate that repeated brain injury is a graver form of traumatic disease of the brain. As compared to the primary injury, patients with repeated craniocerebral injury manifest more pronounced general cerebral, focal hemispheric symptomatology. In such patients, stem symptoms are also encountered more often. Analysis of 163 cases has demonstrated that the clinical manifestations of repeated craniocerebral injury depend on the gravity of the primary and repeated brain injury, age of the victims and by the rate of repeated injuries.

[Diagnosis and treatment of brain contusions in patients with arterial hypertension]. / Diagnostika i lechenie ushibov golovnogo mozga u bol'nykh arterial'noi gipertenziei.

From comparative analysis of 408 cases of brain contusion it is shown that arterial hypertension influences, essentially at times, the informativeness of some diagnostic indices. The sequence of the therapeutic measures in patients with arterial hypertension is determined by the trend of the secondary reactions of the brain to the contusion: the hemorrhagic type of vascular disorders in the first hours and days after the trauma and subsequently by secondary (mainly ischemic type) cerebral circulatory disorders.

[The characteristics of craniocerebral trauma in diffuse toxic goiter]. / Osobennosti cherepno-mozgovoi travmy pri diffuznom toksicheskom zobe.

The specific features of craniocerebral trauma in diffuse toxic goiter were studied from analysis of 34 cases. The craniocerebral trauma aggravated the course of diffuse toxic goiter with the development of thyreotoxic crises in the first days after the trauma in one of five patients. The therapeutic tactics in thyreotoxic crisis and the preoperative and postoperative management of patients are discussed.

[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.

[Prevention and treatment of postoperative complications of acute traumatic intracranial hematoma]. / Profilaktika i lechenie rannykh posleoperatsionnykh oslozhnenii pri ostrykh travmaticheskikh vnutricherepnykh gematomakh.

Timely application of adequate diagnostic and therapeutic measures, reoperations among others, allows mortality to be reduced to 33% in postoperative epidural hematomas, to 50% in recurrent intracranial hematomas, and by 19% in edema and swelling of the brain with its compression. Methods of neurosurgical prevention of complications, the use of an inflow-outflow dialysis system and removal of crushed brain areas attendant to the hematomas in the first place, are the leading factor in improving the outcomes of the treatment of acute traumatic intracranial hematomas.

[Local cerebral blood flow, vascular reactivity and intracranial pressure in the very acute period of a cerebral concussion (experimental)]. / Mestnyi mozgovoi krovotok, sosudistaia reaktivnost' v vnutricherepnoe davlenie v ostreishem periode ushiba golovnogo mozga (v éksperimente).

Changes of local cerebral blood flow, vascular reactivity, and intracranial pressure in the first hours after brain contusion in its different areas (hemispheres, brain stem) were studied in experiment. The dynamics of changes of these values and their interrelationship in the first 2 hour after trauma were revealed.

[Features of the clinical manifestation of contusion of the cerebral hemisphere in patients with hypertension]. / Osobennosti klinicheskikh proiavlenii ushibov polusharii bol'shogo mozga u bol'nykh gipertonicheskoi bolezn'iu.

Analysis of 401 cases with contusion of the cerebral hemispheres showed that in patients with craniocerebral trauma and essential hypertension the incidence of traumatic intracranial hematoma was 1.3-1.4 times higher and the incidence of acute cerebral circulatory disorders (mainly cerebral infarctions) was 4-5 times higher. Isolated contusion of the cerebral hemispheres in patients with essential hypertension was characterized by less manifested symptoms of internal hypertension and the dislocation syndrome. The combination of craniocerebral injury and essential hypertension has a marked effect on the clinical manifestations of both the craniocerebral trauma and essential hypertension.

[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.

[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.

[Multiple primary brain tumors]. / O mnozhestvennykh pervichnykh opukholiakh golovnogo mozga.

This is a write-up of 32 studies of patients suffering from multiple primary brain tumours. Such tumours are encountered quite rarely. Meningiomas, as well as their combination with tumours of another histological structure (neurinomas, gliomas) were most often studied among multiple primary brain tumours. Multiple gliomas occur even more rarely; they may be of a varying degree of malignancy and different in histological structure. Questions of histological structure, the peculiar features of the clinical picture, diagnosis and surgical treatment of patients with this pathology are discussed. A very rare case of multiple primary sarcomas of the brain is described.

[Craniocerebral trauma and stroke]. / Cherepno-mozgovaia travma i mozgovoi insul't.

It was demonstrated from analysis of 685 cases that craniocerebral injury is attended by the development of secondary acute disorders of cerebral circulation in 8.9% of cases. Cerebral apoplexy is encountered in craniocerebral trauma 4-5 times more frequently (in 25% of cases) among patients with arterial hypertension and 2-2.5 times more frequently (in 12% of cases) among those with diabetes mellitus than in patients with a nonacerbated somatic anamnesis (in 5.4% of cases).

[The characteristics of closed craniocerebral trauma in older persons]. / Osobennosti zakrytoi cherepno-mozgovoi travmy u lits starcheskogo vozrasta.

It is shown that in the recent 2 decades the incidence of craniocerebral trauma increased from 4.8 to 7.2% among old-aged individuals and from 53 to 72% in the group of patients over 60. The dynamics of changes in the clinical course of mild craniocerebral trauma in 21% of old-aged patients were marked by secondary acute cerebral circulatory disorders which often led to a fatal outcome. Mortality rate in craniocerebral trauma at old age was 52.3%.

[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.

[Surgical treatment of contusion foci in different age groups]. / Khirurgicheskoe lechenie kontuzionnykh ochagov u postradavshikh razlichnykh vozrastnykh grupp.

The specific features of surgical treatment of contusion foci in patients of various age groups were studied basing on analysis of 606 cases. Two groups of cases were analysed: those with an isolated brain contusion and cases with contusion and compression of the brain by hematoma and bone fragments. It is shown that removal of the contusion foci in patients of various age groups improves the results of treatment. The patient's age has an essential influence on the choice of surgical tactics in brain contusion.

[The use of myelopid in the combined treatment of infectious-inflammatory complications in the postoperative period in neuro-oncology patients]. / Primenenie mielopida v kompleksnom lechenii infektsionno-vospalitel'nykh oslozhnenii v posleoperatsionnom periode u neiroonkologicheskikh bol'nykh.

Clinical observations over 48 neurosurgical patients with infectious inflammatory complications and study of their immune status showed that a course of immunocorrective therapy with myelopid produces a favourable clinical effect and normalizes the patient's immune status. Myelopid causes the best normalizing effect in patients with nontumorous pathology of the central nervous system and in extracerebral neoplasms.

[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.