Kazakov V.Е., Davidchuk A. V.

SE “Lugansk state medical university”

IMMUNOLOGICAL AND BIOCHEMICAL DISTURBANCES IN REMOTE PERIOD OF TRAUMATIC BRAIN INJURY

Introduction. Traumatic brain injury (TBI) is one of the most common causes of disability and death. In most cases after the TBI, appear severe psychotic and neurological disorders. At the same time, during the first 3-4 years structural brain changes are not present.

Objectives. The aim was to determine the possibility of dependence between the clinical condition and immunological and biochemical peculiarities.

Methods. The study involved 97 patients with disease duration of 1 year to 3 years. By the type of mental disorders studied were divided in such way: paranoid disorder, chronic hallucinosis, hysterical disorder, depression, manic, pseudopsychopatical disorder, amnesic syndrome, post commotion syndrome. 41% of patients have cognitive impairment. The control group was represented by patients with TBI not led to long-term effects. All of the examined patients of the main group was conducted detailed clinical and psychopathological, neurological examination, neuropsychological research, tool (MRT and CT). The examination included also neuropsychological study. In the neuropsychological study was used a set of tests CogState, which were used to study the long-term, short-term memory, visual, spatial, emotional, as well as tests on cognitive, motor, and senso-motor learning. The study was conducted in long period of time. Whenever possible, patients began the study if underwent a traumatic brain injury in a period of not more than one year and continued for at least 3 years. Statistical processing of the material was carried out on the personal computer using Microsoft Exel-2010.

Results. We noted particularly the most common forms of post-traumatic disorders. A distinctive feature of the postcommotion syndrome is heavy, poorly amenable to correction asthenia. The peculiarity of paranoid disorder - the presence of paranoid or paraphrenic delusions combined with a change of personality that manifests itself in patient’s hypersocialization. We can see paranoid idea combined with asthenia and psychoorganic disorder. Hallucinosis manifested in the form of true tactile and false visual hallucinations pretentious sense. Manic condition have features angry manic, depression condition have features dysphoria. Psychopathic disorders are shown in the form of difficult polymorphic complex of symptoms with asthenia, vegetative, hysterical, depressive and psychoorganic components. Eventually pathological transformation of traumatic depressive disorder in the outlined affective; sensitive - in the paranoid disorders, explosive - in organic disorders are possible. Besides, by the neuropsychological methods, the study revealed subclinical symptoms (disorder memory) that predict flowing of TBI, including the possibility of psychotic disorders. As it turned out, a persistent breach of cognitive learning, identified neuropsychological, is a prerequisite for the emergence of psycho-organic syndrome, and violation of the emotional memory - for the emergence autisation. Furthermore, in the late period effects of TBI observed relationship between insomnia and psychopathological symptoms. Insomnia was predictor of psychopathology. The problem for many patient with trauma brain injury are insomnia. Insomnia is not only lack of sleep but rather faulty perceptions of their sleeping patterns. Sleep disorders have some features, mainly quantitative, dependent on the variant of a psychopathological syndrome.

Patients with traumatic disorder have color, panic, horrible dreams, they were suffered from nightmares, wake up hallucination. Patients with cognitive disorder suffer from snore, sleep apnea, sleepwalking, wake up hallucination.

During the first 2-3 years after TBI in 83% of the study group patients symptoms of asthenia and insomnia were constantly prevailing.

1.5-2 years after the brain injury in the study group, reduction of level and disorders of melatonin rhythm synthesis were detected in 69% of cases, which was associated with insomnia, flattened diurnal temperature curve and uncontrollable asthenia. In the future, patients with disorders of melatonin synthesis have so-called psychopathological "heat lightnings". There is a direct interference between the daily rhythm’s disorders (melatonine level decreasing, disturbances of its synthesis, insomnias, flattering of the temperature curve) and mental disorders. Was discovered a definite regularity in the formation of mental disorders at the late period of the traumatic brain injury.

3 years after traumatic brain injury in the study group patients using the flow cytometry, we discovered, that in patients with remote effects of traumatic brain injury number of NK-cells is a 200% higher than in healthy individuals. In the cytoplasm of NK-cells are so called cytolytic granules, derived from lysosomal proteins and containing cytolytic proteins. They include perforin and granzymes. Perforin monomers embedded in the cell membrane, polymerize and form a pathological pores. Through pores the cell receives granzymes. They activate the caspase cascade of self-destruction of target cells, i.e., induce apoptosis in cells. The content of population Granzyme B+ - cells in the treatment group was 63.9%, while in healthy content Granzyme B+ was only 31%. The occurrence of apoptosis was obviously provoked by the protracted inflammation and impaired blood-brain barrier. In lymphocyte cultures appeared blast forms of cells, increased expression of CD95+, increased the number of AnV+ cells, involved in apoptosis. There was a loss of the mitochondria ability to maintain a membrane potential, which is associated with the suppression of the antioxidant function of inhibiting apoptosis protein bcl-2. By lowering the transmembrane potential (Dy_m) and pore formation proapoptogenic factors (cytokines) entered into the cytoplasm and invoke caspase cascade. Clinically that looked like violation of the general condition, as well as the appearance of psychopathological hallucinatory and delusional affective "lightning" and led to worsening of the patients’ general condition and growing asthenic, depressive, anxiety symptoms, with the appearance of pseudo-psychopathic, hallucinatory-paranoid features and cognitive impairment. In the control group, asthenic symptoms were less obvious, unlike in the study group, their sleep-wake cycle was normal, and increased apoptosis and disorders of melatonin synthesis were not detected.

Conclusions. There is a direct dependence between the clinical condition of TBI and immunological, biochemical (melatonine), cytological (apoptosis induction) disorders, that should be paid attention to at diagnostics and differential diagnostics.