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

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     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.


Project Roles:

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