The Effect of Brain Injuries on the Quantitative Ratio and Functional Activity of Peripheral Blood Leukocytes

The dissertation is dedicated to studying the effect of brain injuries — traumatic brain injury and ischemic stroke — on the quantitative ratio and functional activity of peripheral blood leukocytes. The research encompasses changes in the leukocyte formula, morphocytochemical indicators of lymphocytes, and the state of microbicidal systems of neutrophils. The work was carried out at Surgut State University and includes the analysis of groups of patients with traumatic brain injury, patients with ischemic stroke, and practically healthy individuals.

Research Relevance. In recent times, a significant increase in the number of brain injuries, including among individuals of working age, has been noted, accompanied by a high level of mortality and disability among the affected [1, 77, 178, 179, 238]. Among traumatic brain injuries, mild traumatic brain injury is the most common (up to 70% of the total number of neurotrauma) [180]; and in the structure of acute cerebral circulation disorders, ischemic stroke accounts for the major share (up to 80% of all strokes) [46, 240].

Brain injuries lead to the development of complex pathophysiological disorders in patients. Among the most important components of pathogenesis, immunopathological processes are currently recognized, the main clinical manifestations of which are infectious complications [44, 113, 222, 235].

Disorders of the immune status of the organism arise within the first days of nervous system injury [153] and persist for a long time after clinical recovery [32]. Timely diagnosis of the severity of the lesion, assessment of the state of major organ systems, and the dynamics of the pathological process serve as the basis for prescribing adequate treatment and determining the individual prognosis [90].

The blood system plays a crucial role in the development of the organism's response to brain injury, owing to the multifaceted nature of its functions and its ability to sensitively and promptly react to external influences. This property of blood cells is utilized in the study of various hematological indicators, particularly those characterizing the white blood cell series [90, 167, 224, 231]. Based on the indicators of the quantity and ratio of various types of peripheral blood leukocytes and their functional activity, the onset and dynamics of pathological processes in the organism can be determined. In this regard, changes in morphocytochemical indicators of blood cells arise earlier than changes in leukogram values, reflect deeper metabolic disturbances, and appear before clinical symptoms [129, 172]. The pathophysiological significance of changes in these parameters in brain injuries has not yet been definitively established.

The majority of works devoted to studying the immune status in brain injuries focus on the investigation of cellular (T- and B-lymphocytes, phagocytic activity of leukocytes) and humoral factors of immunity (immunoglobulins, cytokines, complement components) [37, 69, 68, 83, 139, 170, 181, 197]. Only in isolated publications are questions concerning the state of microbicidal systems of neutrophils in brain injuries addressed [33, 89, 113, 218]. The results of these studies are fragmented and contradictory. The morphological features of peripheral blood lymphocytes and the activity of RNA synthesis in lymphocyte nuclei have also been insufficiently studied. This determined the relevance of the present study.

The objective of the study: to investigate the effect of brain injuries on the quantitative ratio and functional activity of peripheral blood leukocytes.

Tasks of the study:

1) To evaluate changes in the quantity and ratio of various morphological forms of peripheral blood leukocytes in patients with brain injuries.

2) To evaluate morphocytochemical indicators of peripheral blood lymphocytes in patients with brain injuries.

3) To study the state of microbicidal systems of peripheral blood neutrophils based on myeloperoxidase content and lysosomal cationic proteins in patients with brain injuries.

4) To conduct an analysis of the interrelationships of morphocytochemical indicators in patients with brain injuries.

The work was carried out within the framework of the departmental research program «Medical-Ecological Monitoring of the Health Status of the Indigenous and Settler Population of the Khanty-Mansi Autonomous Okrug — Yugra» (state registration No. 0120406834).

Scientific Novelty of the Study.

For the first time, the informativeness of integral hematological indicators in brain injuries of different etiology has been determined.

For the first time, changes in the activity of the nucleolar apparatus and morphometric indicators of peripheral blood lymphocytes in traumatic and ischemic brain injuries have been demonstrated.

For the first time, changes in the microbicidal systems of neutrophilic leukocytes of peripheral blood in brain injuries of different etiology have been evaluated.

For the first time, the difference in the nature of the relationships between microbicidal systems of neutrophilic leukocytes, the activity of the nucleolar apparatus of lymphocytes, and morphometric indicators in brain injuries depending on the severity of the pathological process has been demonstrated.

Practical Significance of the Work.

The diagnostic significance of integral hematological, morphological, and cytochemical laboratory indicators of peripheral blood leukocytes for assessing the nature and severity of brain injuries has been demonstrated.

The results of the study have been implemented in the practice of the Regional Hospital «Trauma Center» of Surgut and the Neurovascular Department of the Surgut Regional Clinical Hospital.

Main Provisions Presented for Defense:

1. In brain injuries, one of the links in the pathological process is the alteration of the quantitative ratio of peripheral blood leukocytes: an increase in the content of phagocytes (neutrophils and monocytes) and a decrease in the number of lymphocytes.

2. The effect of brain injuries on immunocompetent cells of peripheral blood manifests itself in the activation of the nucleolar apparatus of lymphocytes, an increase in the activity of oxygen-independent and a decrease in the activity of oxygen-dependent microbicidal systems of neutrophils.

3. The relationship between indicators of microbicidal systems of neutrophilic leukocytes and indicators of the activity of the nucleolar apparatus of lymphocytes in brain injuries manifests differently depending on the nature of the injury — in mild and moderate traumatic brain injury, this is a strong positive correlation, while in ischemic stroke, it is a strong negative correlation.

Dissertation Defense Validation.

The main provisions and results of the study were presented as publications and reports at the Open Regional Conference of Young Scientists «Science and Innovations of the XXI Century» (Surgut, 2003); the International Scientific Conference «Medical-Biological and Ecological Problems of Human Health in the North» (Surgut, 2004); the V Open Regional Conference of Young Scientists «Science and Innovations of the XXI Century» (Surgut, 2004); and the XIV All-Russian Conference «Neuroimmunology» (St. Petersburg, 2005).

Publications of the Research Results.

15 printed works have been published on the dissertation topic.

Volume and Structure of the Dissertation. The dissertation is presented on 125 pages of typed text, illustrated with 11 figures, 33 tables, and consists of an introduction, literature review, materials and methods of research, three chapters of original research, conclusion, findings, practical recommendations, and a list of references. The bibliography contains 247 sources, of which 181 are by domestic and 66 by foreign authors.