Preconditioning With Gamma Ray Irradiation Induces Neuroprotection Against Ischemia-reperfusion Insult: A 31p-nmr Study

Osamu Tokumaru1, Chihiro Kuroki1, Hiroyuki Kenai2, Hirofumi Nagatomi3, Isao Yokoi1

1Oita University 2Oita, Japan 3 Nagatomi Neurosurgical Hospital

Keywords: perfusion, ischemia, radiation injury, neuroprotection, gamma knife

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Abstract

     The authors previously reported that preconditioning with subnecrotic gamma ray irradiation induces bioenergetic tolerance and thereby remodels energy metabolism of rat brain that is crucial for postischemic recovery in ischemia-reperfusion insult.
     The authors further investigated whether gamma ray preconditioning is dependednt on neurons or on astrocytes by assessing bioenergetic dynamics of rat brain using phosphorous nuclear magnetic resonance (31P-NMR).
      
     In Exp-1, rat brain was irradiated with 60Gy by Gamma Cell 40 Exactor (MDS Nordion, Ottawa, Canada). One week after the irradiation, the animal was sacrificed and the brain slices (400 µm-thick) were incubated in standard artificial cerebrospinal fluid (ACSF) bubbled with 95% O2 and 5% CO2 gas mixture at 25°C. The slices were exposed to ischemic insult by halting the perfusion for 64 min followed by the recovery period for 128 min. Levels of high-energy phosphates, phosphocreatine (PCr) and ?-ATP, were measured by 31P-NMR. In Exp-2, rats are fixed on a Régis-Valliccioni frame and irradiated in the right hemisphere by Leksell Gamma Knife 4C (Gamma Knife Center, Nagatomi Neurosurgical Hospital, Oita, Japan) with 50% isodoze line of 60 Gy covering the whole right cerebrum. 31P-NMR study is performed to compare high energy phosphate levels between bilateral hemispheres of each rat.
     In Exp-1, the recovery of PCr after ischemia-reperfusion insult was significantly better in the preconditioned brain by gamma ray than in the control (n = 8, p = 0.009). But no difference was observed when slices were pretreated with fluorocitrate, a selective astrocytic poison (n = 6). Exp-2 is now under way to confirm the findings of Exp-1.
     This is a retrospective study.
     Preconditioning with non-necrotic gamma ray induced neuroprotective effect against inshemia-reperfusion insult, but it did not induce the effect without the presence astrocytes.
      Those findings indicated that low-dose gamma-irradiation remodels bioenergetic dynamics of the brain including the astrocyte-neuron lactate shuttle, which connects energy metabolism and neuronal functions. Exp-2 is being executed in order to elucidate the effect by comparing the paired data (irradiated vs control hemisphere) within a rat.


Acknowledgements

Project Roles:

O. Tokumaru (), C. Kuroki (), H. Kenai (), H. Nagatomi (), I. Yokoi ()