The effect of progesterone on cardiomyocytes in traumatic brain injury: A randomized study

Objective: Traumatic brain injury (TBI) is one of the leading causes of death and disability in the world, especially among young people of working age.In addition to direct brain damage, TBI causes repercussive organ changes, including dysfunction of the cardiovascular system, which worsens the prognosis of patients.Currently, there are no effective medicines for the treatment of TBI, and the search for new neuroprotective and cardioprotective drugs remains an urgent task.Progesterone, widely used in gynecology, has demonstrated neuroprotective properties in experimental models of TBI, but its effect on the heart during trauma has not been sufficiently studied.The aim of the study was to study the effect of progesterone on the morphological state of cardiomyocytes in acute TBI.Methods: The experiment was conducted on 15 sexually mature outbred male rats (200-250 g), divided into three groups of 5 individuals: intact (control), with simulated acute TBI without treatment, and with TBI treated with progesterone (10 mg/kg 1 and 24 hours after injury).The closed TBI model was reproduced by the fall of a metal weight (68 g) from a height of 1 m, creating an impact force of 0.6 J. On the 3rd day after the injury, the animals were removed from the experiment and a morphological analysis of the heart was performed.Myocardial samples were fixed, stained, and studied under a light microscope with cardiomyocyte morphometry (thickness, area, nuclearcytoplasmic ratio, pycnotic index).Statistical data processing was performed using SPSS 16.0, the Student's t-test was applied at p < 0.05.Results: On the 3rd day after the induction of moderate TBI cardiomyocytes exhibited changes including loss of their cylindrical shape, disruption of transverse striation, cytoplasmic vacuolization, as well as signs of apoptosis and necrosis.Cell nuclei were deformed, hyperchromatic, and showed karyorrhexis, accompanied by a significant reduction in morphometric parameters of cardiomyocytes: cell length decreased from 95.2 (4.8) to 73.6 (3.9) m, cross-sectional diameter decreased by 23%, and cross-sectional area decreased by 28% compared to the control group (p<0.05).Nuclear diameter decreased from 7.2 (0.5) to 5.3 (0.4) m, and the nuclear-cytoplasmic ratio fell by 27%.Progesterone administration contributed to partial restoration of morphometric parameters: cardiomyocyte length increased to 85.7 (4.1) m, and cross-sectional diameter to 12.6 (1.0) m.The frequency of pyknotic nuclei decreased, and the number of necrotic cells was reduced.Morphologically, preservation of transverse striation, orderly arrangement of cardiomyocytes, and diminished signs of inflammation were observed. Conclusion:The data obtained indicate the ability of progesterone to partially restore the structure of the heart muscle and reduce degenerative processes, which opens up prospects for complex therapy of patients with TBI.