Dovgan I. Structural and metabolic characteristics of demyelinating process after hemorrhagic stroke and the ways of its correction

The dissertation is devoted to the study of delayed neurodegenerative changes in the nervous system after hemorrhagic stroke. Numerous patterns of demyelination and degenerative changes in the brain, spinal cord and the sciatic nerve in the acute and remote periods after a stroke have studied. In experimental study the ultrastructural signs of demyelinating and degenerative changes in the cerebral cortex, corpus callosum, internal capsule, lateral corticospinal tract and the bilateral progressive morphological changes of nerve fibers in the sciatic nerve were detected at 10, 30 and 90 days after right-brainhemorrhagic stroke. It was found that the brain swelling and degeneration changes not limited the perifocal are in internal capsule and progressed to contralateral brain cortex, corpus callosum and L3-L5 lateral funiculi. The analysis of nerve fibers morphology showed the development of neurodegenerative changes, which consisted in progressive demyelination, deformation and atrophy of myelin nerve fibers, and edema of non-myelin fibers. Those changes in the left sciatic nerve are more progressive versus the right nerve, up to the complete degeneration of the nerve fibers in the nerve's fascicles of the paretic limb on 90 day. The results of transmission and scanning electron microscopy have shown intact the main stromal elements of the nerve (epineurium and perineurium) and the reduction of nerve fibers density, which was suppressed by pharmacocorrection (piracetam, corvitin with lipin) in acute period of stroke (10 days). Electrophysiological and morphological values of the left and right nerves in rats after stroke with/without pharmacological correction were compared. The electrophysiological study has shown a statistically significant decrease in conduction velocity of the sciatic nerve on 30th and 90th day of stroke. The early structural changes in the nerve on the 10th day of stroke (deformation and decrease the thickness and density of nerve fibers) were registered in morphological study. The progress of neurodegeneration on the 30th and 90th days (loss of nerve fibers and the appearance of free Schwann cells) was also shown. The greater level of degenerative changes in the left sciatic nerve in comparison with the right nerve was verified through the morphometric method. The sciatic nerve conduction velocity on 90th day after the pharmacocorrection by corvitin with lipin was significantly greater compared with 30th and 90th days without treatment. The increase in conduction velocity may indicate on the adaptive and restorative changes in the nerve induced by treatment. The results of histological studies have shown that a unilateral stroke can induce bilateral neurodegeneration in the sciatic nerve, and the proposed pharmacological treatment may result in restore the conduction velocity in the nerve in the long-term period.The results of biochemical studies indicate the activity of antioxidant enzymes changes in the brain and sciatic nerve after stroke. The increased levels of CAT and decreased levels of GR are manifestations of cytoprotective mechanisms imbalance because both of these enzymes are taken part at neutralizing of free radicals through the hydrogen peroxide utilization and restoring the glutathione pool. At the same time neuroprotective and metabolitotropic pharmacocorrection has contributed to the restoration of metabolic processes.Thus, thebrain edema and motor cortex injury afterintracerebral hemorrhage not limited by the local disturbances and caused descending degeneration of the pyramidal tracts.