Disordered distribution of spleen lymphocytes over phases of the cell cycle in experimental stroke of different severity
Abstract
Background. Impairment of the immune system in stroke plays an important pathogenic role in development of this disease and generally consists at the systemic level of depressed non-specific and cellular immunity, activated humoral immunity, autoimmune reactions, and imbalance of the cytokine system. However, information about the relationship between activity of immunocompetent cells and severity of acute cerebrovascular disease is unavailable.
Aim: To study proliferative activity and distribution of lymphocytes over phases of the cell cycle in stroke of different severity.
Materials and methods: This experimental study was performed on Wistar rats weighing 200-220 g (n=55). Proliferative activity and distribution of spleen T and B lymphocytes in the mitotic cycle were studied in the left hemisphere (capsula interna) on experimental models of mild, moderate and severe stroke. Neurological status of animals was evaluated using the Stroke-index McGraw scale modified by I.V. Gannushkina. Results: Assessment of the neurological status on the 3rd day after the onset of experimental stroke showed that the severity of experimental model corresponded to the severity of neurological status. Stroke was associated with changes in the distribution of B-lymphocytes over the cell cycle phases. This was evident as a decrease in proliferative activity shown by decreased pools of cells in the S-phase, in which DNA replication occurs (mild stroke, 55.3% [52.7; 58.1]; moderate stroke, 53.2% [50.9; 54.7]; severe stroke, 46.2% [44.2; 50.0]) and in the G2/M-phase, in which mitosis occurs (mild stroke, 1.1% [0.9; 1.3]; moderate stroke, 0.8% [0.7; 1.1]; severe stroke, 0.5% [0.5; 0.7]); and by increased pool of cells in the G0/G1 phase, in which mRNA and protein are synthesized (mild stroke, 43.4% [40.8; 46.2]; moderate stroke, 46.1% [44.4; 48.3]; severe stroke, 53.3% [49.6; 55.4]). These differences were significant compared with the control group. These changes increased with severity of the stroke model. A similar tendency was noted for T-lymphocytes in stroke groups – a decreased proportion of cells in the S-phase and an increased cell pool in the G0/G1-phases. However, in the G2/M-phases, the number of lymphocytes was increased (mild stroke, 2.9% [2.6; 3.2]; moderate stroke, 3.8% [3.5; 4.1]; severe stroke, 4.4% [4.1; 4.8]) and significantly different from the control, which indicated active mitosis. These changes increased with the severity of stroke.
Conclusion: acute cerebrovascular pathology results in disordered distribution of splenic T and B lymphocytes over cell cycle phases and decreased lymphocyte proliferative activity; these changes increased with the severity of experimental stroke.