Experimental and Clinical Therapeutics

Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP120) Hyperbaric oxygen improves survival of irradiated CNS astrocytes and neurons.

Hoopes , P. Jack *,1, 2, Yeo, Tet-kin 1, Strawbridge, Rendall1, Sundaram , Sujatha 1, Gladstone , David 2, Paul, Brian 1, 2, Shenberger , Jeffrey 3, Myers , Jeniffer 3, Buckey, Jay 2, O'Hara, Julia2, Hug , Eugne 2, 1 Department of Surgery, Hanover, NH, USA2 Department of Medicine (Radiation Oncology), Hanover, NH, USA3 Department of Pediatrics, Hanover, NH, USA

ABSTRACT- Radiation and surgery remain the most common and effective treatment for malignant brain tumors. However, the efficacy of radiation treatment continues to limited by the radiation tolerance of the normal brain that surrounds the tumor. Although far from being optimized there is now considerable patient data which suggests hyperbaric oxygen therapy can effectively spare some of the complications associated with brain irradiation. Although relatively little is known about the molecular and/or cellular effects of HBO, it is now used routinely to rescue normal tissues that are poorly vascularized (e.g. diabetes complications) or are at risk for complications from irradiation. In these studies we focus on understanding the molecular mechanisms and optimization of hyperbaric oxygen (HBO) sparing of irradiated normal brain tissue. Preliminary findings include : 1. Numerous brain irradiation studies (including our own)have shown astrocytes proliferate following conventional therapeutic brain irradiation. 2. HBO given after radiation improves astrocytes survival as compared to no HBO or HBO given before or simultaneously with radiation. 3. Clonogenic studies indicate that the survival of irradiated CNSA (astrocytes from CNS)increased significantly (84.6%)when exposed to 1.5 ATA of HBO five days following irradiation, 5 Gy at a dose rate of 100 rads/min. No significant changes were observed when was HBO given before or simultaneously with radiation or in other cultured CNS cells (endothelial cells or oligodendrocytes) 4. A significant decrease in ERK1, FAK, p38 MAPK, and PKR was observed following HBO treatment of irradiated CNSA cells. Although it is still unclear how this finding relates to increased astrocyte and neuron survival, it is possible that these phosphoproteins (especially MPAK) have a role in the functionality of the astrocytes. 5. Histomorphometric studies in irradiated and/or HBO treated mouse brains confirmed the in vitro study results. There was a significant increase in the survival of astrocytes and neurons in irradiated brain tissues(5 x 6 Gy) which received a 1.5 hour HBO treatment (1.5 ATA) 21 days following irradiation.

Key words: brain, radiation injury, hyperbaric oxygen, tissue sparing

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2005 RRS