Acta Neuropathologica

, Volume 110, Issue 2, pp 120–126 | Cite as

Evaluation of the apoptosis-related proteins of the BCL-2 family In the traumatic penumbra area of the rat model of cerebral contusion, treated by hyperbaric oxygen therapy: a quantitative immunohistochemical study

  • Eugene VlodavskyEmail author
  • Eilam Palzur
  • Moshe Feinsod
  • Jean F. Soustiel
Regular Paper


The growth and progression of traumatic brain injury (TBI) lesions depend significantly on developments in the traumatic penumbra area, perilesional region, where delayed neuronal death occurs. Recent data supports the important role of apoptosis in delayed cell death in TBI. Previously we demonstrated a significant reduction of apoptosis in traumatic penumbra in animals treated by hyperbaric oxygen (HBO).In this study we evaluate the expression of apoptosis-related proteins of the Bcl-2 family (Bcl-2, Bax and Bcl-xL) in the traumatic penumbra area in correlation with the extent of apoptosis in the rat model of focal cerebral contusion, treated by HBO. Sprague-Dawley rats underwent cortical dynamic deformation, some with subsequent hypoxemia. A group of both hypoxemic and non-hypoxemic animals was treated by HBO. The pathological study was based on immunohistochemical staining of the brain sections for Bcl-2, Bax and Bcl-xL with quantitative evaluation of staining by image analysis. The expression of Bcl-2 in hypoxemic animals was lower than in non-hypoxemic animals, but a significant increase in Bcl-2 expression was seen in both groups after HBO treatment. Bcl-xL also demonstrated an increase after HBO treatment but less significant. Staining for Bax protein did not demonstrate significant change after treatment. These data correlate well with the reduction of TUNEL-positive cells in traumatic penumbra after HBO treatment. We concluded that the apoptotic mechanisms are important in delayed cell death in TBI and that post-traumatic hypoxemia increases the intensity of apoptosis, probably through a decrease in Bcl-2 and Bcl-xL expression which normally repress apoptosis. The beneficial effect of HBO treatment in our model of brain contusion correlates well with the increased expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL) following treatment and the appropriate decrease in the extent of apoptosis. In light of these results, the usage of HBO is justified as neuroprotective treament in TBI.


Apoptosis Bcl-2 Hyperbaric oxygen Traumatic brain injury 



The authors gratefully acknowledge the expert technical assistance of Shoshana Ben-Eliezer, Irina Minkov and Inna Grinberg with histological and immunohistochemical methods. The authors also thank Myrna Perlmutter for her help in the preparation of this paper.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Eugene Vlodavsky
    • 1
    Email author
  • Eilam Palzur
    • 2
  • Moshe Feinsod
    • 2
  • Jean F. Soustiel
    • 2
  1. 1.Institute of PathologyRambam Medical Center and Faculty of Medicine, Technion-Israel Institute of TechnologyHaifaIsrael
  2. 2.Department of Neurosurgery and Acute Brain Research LaboratoryRambam Medical Center and Faculty of Medicine, Technion-Israel Institute of TechnologyHaifaIsrael

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