Significance of Immunohistochemical Studies of Heat Shock Proteins of the HSP70 Family in the Investigation of Postresuscitative Brain Changes

Objective: to evaluate the immunological responsiveness of various neuronal populations of heat shock proteins of the HSP 70 family and to reveal their association with the magnitude of postresuscitative neuronal morphological changes.

Materials and methods. The hypoxia-highly sensitive neuronal populations of pyramidal neurons in the layer of the fifth cerebral sensomotor cortex and hippocampal sectors CA1 and CA4 throughout the postresuscitative period after 12-minute cardiac arrest were subject to a complex immunocytochemical and morphometric study. Their immunological responsiveness to the thermal shock proteins was determined by the indirect peroxidase-antiperoxidase test using the polyclonal antibodies to HSP70. The density and composition of neuronal populations were ascertained by the morphometric assay.

Results. The baseline immunological responsiveness of neuronal populations has been demonstrated to be an important factor of its resistance to ischemic lesions. The authors have determined a trend in postresuscitative changes in the immunological responsiveness of neuronal populations to HSP70 and established its association with the development of nerve cell dystrophic changes. They discuss whether complex immunocytochemical and morphometric studies are promising in investigating the mechanisms of postresuscitative brain abnormality.

Conclusion. By and large, the findings suggest that the role of HSP70 in maintaining the homeostasis of neuronal populations is more complex and multifactorial, as earlier considered, and it is unlikely to be restricted itself to only merely neuroprotective properties. The high baseline content of HSP70 makes a considerable contribution to the resistance of neuronal populations to ischemia-reperfusion; and the changes in the immunological responsiveness to HSP70 are closely associated with the development of pathological nerve cell changes during a postresuscitative process.

1. Неговский В. А., Мороз В. В. Актуальные проблемы реаниматологии на рубеже XXI века. В кн.: Тез. докл. 2 Рос. конгр. по патофизиологии, 9-12 окт. 2000 г. М.: Медицина; 2000. 302.

2. Аврущенко М. Ш. Изменение гетерогенных нейронных популяций в постреанимационном периоде после остановки сердца у крыс. Анестезиология и реаниматология 1994; 5: 41—44.

3. Lipton P., Raley-Susman K. M. Autoradiographic measurements of protein synthesis in hippocampal slices from rats and guinea pigs. Methods 1999; 18 (2): 127—143.

4. Neuman R. W. Molecular mechanisms of ischemic neuronal injury. Ann. Emerg. Med. 2000; 36 (5): 483—505.

5. White B., Sullivan J., DeGracia D. et al. Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J. Neurol. Sci. 2000; 179: 1—33.

6. Yao X.-H., Yu H.-V., Koide S., Li X.-J. Identification of a kay protein associated with cerebral ischemia. Brain Res. 2003; 967 (1—2): 11—18.

7. Liu M., Alkaued N. Hypoxic preconditioning and tolerance via hypoxia inducible factor (HIF) 1alfa -linked induction of P450 2C11 epoxygenase in astrocytes . J.Cereb.Blood Metab. 2005; 25 (8): 939—948.

8. Jin K., Mao X., Eshoo M. et al. Microarray analysis of hippocampal gene expression in global cerebral ischemia. Ann. Neurol. 2001; 50 (1): 93—103.

9. Fredduzzi S., Mariucci M. T., Ambrosini M. V. Generalized induction of 72-kDa heat-shock protein after transient focal ischemia in rat brain. Exp. Brain Res. 2001; 136: 19—24.

10. Giffard R., Lijun Xu., Heng Zh. et al. Chaperones, protein aggregation, and brain protection from hypoxic/ischemic injury. J. Experim. Biol. 2004; 207: 3213—3220.

11. Bottiger B.W., Schmitz B., Wiessner C. et al. Neuronal stress response and neuronal cell damage after cardiopulmonary arrest in rats J. Cereb. Blood Flow Metab. 1998; 18: 1077—1087.

12. Kita T. The role of heat shock proteins on the disordered tissues: implication for the pathogenesis and diagnostics in the forensic practice. Nippon Hoigaku Zasshi 2000; 54: 367—371.

13. Franklin T. B., Krueger-Naug A. M., Clarke D. B. et al. The role of heat shock proteins Hsp70 and Hsp27 in cellular protection of the central nervous system. Int. J. Hyperthermia 2005; 21 (5): 379—392.

14. Корпачев В. Г., Лысенков С. П., Тель Л. З. Моделирование клинической смерти и постреанимационной болезни у крыс. Патол. физиология и эксперим. терапия 1982; 3: 78—80.

15. Аврущенко М. Ш. Изучение популяции клеток Пуркинье коры мозжечка собак, перенесших остановку системного кровообращения. Бюл. эксперим. биологии и медицины 1981; 93 (12): 8—11.

16. Аврущенко М. Ш., Саморукова В. В., Мороз В. В. и др. Развитие постреанимационных морфологических изменений нейронов гиппокампа и мозжечка: общие закономерности и особенности. Патол. физиология и эксперим. терапия 2003; 2: 27—30.

17. Аврущенко М. Ш., Маршак Т. Л., Фатеева В. И. и др. Интенсивность синтеза белка в различных областях мозга крыс, перенесших остановку системного кровообращения. Анестезиология и реаниматология 1993; 2: 43—46.

18. Аврущенко М. Ш., Маршак Т. Л. Синтез белка в нейронах и сателлитных глиальных клетках после глобальной ишемии мозга, вызванной остановкой сердца у крыс. Бюл. эксперим. биологии и медицины 1997; 123 (3): 257—260.

19. Plumier J. C., Krueger A. M., Currie R. W. et al. Transgenic mice expressing the human inducible HSP70 have hippocampal neurons resistant to ischemic injury. Cell Stress Chaperones 1997; 2: 162—167.

20. Yenari M. A., Fink S. L., Sun G. H. et al. Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy. Ann. Neurol. 1998; 44: 584—591.

21. Lee J. E., Yenari M. A., Sun G. H. et al. Differential neuroprotection from human heat shock protein 70 overexpression in in vitro in vivo models of ischemia and ischemia-like conditions. Exp. Neurol. 2001; 170: 129—139.

22. Christians E., Yan L.-J., Benjamin I. Heat shock factor 1 and heat shock proteins: critical partners in protection against acute cell injury. Crit. Care Med. 2002; 30 (1): 43—50.

23. Yenari M. A., Liu J., Zheng Z. et al. Antiapoptotic and anti-inflammatory mechanisms of heat-shock protein protection. Ann. N.Y. Acad. Sci. 2005; 1053: 74—83.

24. Klettner A. The induction of heat shock proteins as a potential strategy to treat neurodegenerative disorders. Drug News Prospect 2004; 17 (5): 299—306.