MORPHOFUNCTIONAL PECULIARITIES OF ISCHEMIC AND HEMORRHAGIC INJURIES OF THE BRAIN IN RATS AT THE MODELING OF THE EFFECTS OF MICROGRAVITATION
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1
Federal Research and Clinical Center, Federal Medical-Biological Agency, Russia
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2
Research Institute of General Pathology and Pathophysiology, the Russian Academy of Medical Sciences, Russia
Information on the effects of microgravity at the central nervous system (CNS) is still fragmentary. At the same time, cognitive functions: memory, ability to learn and analyze situations, make decisions - can also change under microgravity. Besides, cerebro-vascular changes can impact the onset and course of both cerebral ischemic and hemorrhagic stroke if it occurs during the space flight.
Purpose: To assess microgravity effects at the formation of specific features in the development of brain injuries of various etiology.
The rat suspension model was used for modeling microgravity.
Several experiment series were made in which suit suspension (SS) of various duration preceded to or was made after experimental brain injury.
For the experimental model of ischemic stroke, photochemical thrombosis of blood vessels in the prefrontal cortex was used.
Cognitive functions of rats' brain were studied by developing a conditioned passive avoidance reflex (CPAR) [1]. CPAR stability was defined with latent period (LP).
Model of hemorrhagic stroke. A transplant consisting of crushed hemostatic collagen sponge and blood plasma of rabbit was injected into the cortex motor zone in the left hemisphere into the area which is responsible for movements of animal's right front paw.
There were several groups of rats in this experiment:
Group1. Typical hemorrhagic stroke. Transplant contains acellular blood plasma.
Group 2. Typical hemorrhagic stroke. Transplant contains blood plasma rich with platelets containing angiogenesis stimulation factors (PRP).
Group 3. Typical stroke. Transplant (PRP). 7 days of SS after stroke.
Group 4. 7 days of SS. Typical stroke. Transplant (PRP).
Group 5. 2 days of SS. Typical stroke. Transplant (PRP).
Group 6. Vivarium control.
Animals' functional state was assessed with their motor activity. Motor activity was examined before surgery and on day 7 after it using test "walking on bar".
Morphological findings were used for defining: vasculature development, blood vessels caliber, neurons content, gliocytes, infiltrate cells; location density of binuclear neurons.
Results:
Microgravity negative impact at rats' cognitive functions was revealed even without additional pathological damage.
After exposure to microgravity in EG, average values of motor activity and CPAR indices were not significantly different from the baseline values. It was noted decrease in LP CPAR. In CG, motor activity was reliably reduced in comparison to initial levels after 14 days of staying in normal vivarium conditions, while CPAR latent period remained unchanged. Decreased motor activity in the control group and a conditioned passive avoidance reflex demonstrate that cognitive functions were preserved, since animals show less "interest" to repeated presentations to familiar "open field" device environment and keep in their memory unpleasant sensations of electric shock (CPAR). On the other hand, findings in experimental animals can be regarded as an adverse SS effect at cognitive functions. Less transition latent period indicates weakened conditioned passive avoidance reflex; animals have motor activity on the "open field" similar to the pre-experimental level what shows weak fixation of the information obtained during the first testing.
Than we studied an impact of ischemic stroke at cognitive functions and at the structure of brain prefrontal cortex. Animals were divided into control and experimental groups. For 14 days, controls were in vivarium, while experimental animals were in SS. On day 7, ischemic stroke was induced with the described procedure in both groups.
We can state that stroke in the prefrontal cortex causes significant memory impairments in rats of both groups, but there are no differences between the groups.
At the next stage, hemorrhagic stroke was chosen as a model of pathological process in brain. Number of binuclear neurons per unit area in rat's cerebral cortex was taken as an indicator of regenerative processes.
The highest mortality rate was in the group in which SS started after stroke modeling; and the lowest mortality rate was in Group 5 in which stroke was preceded by a short-term simulated microgravity.
The best restoration of motor function was in animals from Groups 4 and 5 in which hemorrhagic stroke was preceded by exposure to SS. The worst results were in Group 3.
Morphological examination of brain preparations from animals of Group 1 showed extravasates in the infiltrate, neoangiogenesis. However, vessels grow slowly; they are mostly of small diameter.
Group 2 - much more blood vessels. Vessels were of larger caliber and they were arterioles and venules. Significantly more macrophages; they were most often located in the vessel wall.
Morphological changes in Group 3 demonstrated signs of acute circulatory disorders. Serious circulation impairments - extravasates- which were not seen in Group 2, are often met in Group 3. Many longitudinally cut capillaries which are invisible under normal circulation, now become clearly seen and are indicative of disorders in blood outflow and blood stasis.
Group 4 has a larger number of newly formed vessels than Groups 1 and 3. These vessels are capillaries and more matured vessels - venules and arterioles. All animals of this group had extravasates at the border of infiltrate and penumbra which mainly consisted of loosely lying erythrocytes and rarely met dense clusters. There were no other circulatory disorders, such as blood stasis.
Group 5 has the largest number of newly formed vessels, both in the infiltrate and penumbra. There are no circulatory disorders, such as blood stasis or extravasates.
Groups 3 and 5 significantly differ from the controls with density of binuclear neurons locations. In Group 5, density of fusion locations in the stroke area significantly exceeds similar density at the same part of intact hemisphere. Injury triggers regeneration, but simultaneously it inhibits this regeneration with pathogenic changes in the stroke focus. That is why, regeneration intensity is always a ratio of stimulating and inhibiting factors. In Group 5, this ratio promoted regeneration what was manifested both morphologically and functionally.
The overall good result in Group 5 can be probably explained with effects of short-term microgravity which preceded damage; it increased venous pressure and thereby, contributed to collapse or dilatation of collaterals and anastomoses.
References
1. Bures J., Burešová O., Huston J.P. Techniques and Basic Experiments for the Study of Brain and Behavior., Elsevier, 1976.
Keywords:
ischemic stroke,
Hemorragic stroke,
microgravity,
Rats,
morphology
Conference:
39th ISGP Meeting & ESA Life Sciences Meeting, Noordwijk, Netherlands, 18 Jun - 22 Jun, 2018.
Presentation Type:
Extended abstract
Topic:
Animal Models
Citation:
Baranov
M,
Paltsyn
A,
Romanova
G and
Shakova
F
(2019). MORPHOFUNCTIONAL PECULIARITIES OF ISCHEMIC AND HEMORRHAGIC INJURIES OF THE BRAIN IN RATS AT THE MODELING OF THE EFFECTS OF MICROGRAVITATION.
Front. Physiol.
Conference Abstract:
39th ISGP Meeting & ESA Life Sciences Meeting.
doi: 10.3389/conf.fphys.2018.26.00035
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Received:
02 Dec 2018;
Published Online:
16 Jan 2019.
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Correspondence:
Dr. Mikhail Baranov, Federal Research and Clinical Center, Federal Medical-Biological Agency, Moscow, Russia, baranovm2000@mail.ru