Nuclear accidents or terrorist activities may lead to moderate dose whole body radiation exposure to a mass population. Ionizing radiation is known to influence brain and behaviour. Of all the brain regions, hippocampus is known to be highly sensitive to radiation injury. Radiation induced acute, early delayed and late delayed brain injury is often observed after fractionated partial or whole brain irradiation. However, effect of whole body radiation on brain is still a problem of research to work upon. A few recent studies have observed whole body radiation induced acute changes in brain^1,2. Yet a comprehensive study is required to understand whole body radiation induced changes in brain at all the phases of injury like early delayed or late delayed. Therefore, the present study was planned to study whole radiation induced changes in hippocampus at different phases of radiation injury in animals employing two approaches, behaviour functions and advanced MR techniques.To look for cognitive, metabolic and microstructural changes in hippocampal region at acute, early delayed and late delayed phases of whole body radiation injury.Study was conducted on 120 C57 male mice (8 to 10 weeks old). Out of 120 animals, 60 animals were irradiated with 5Gy of whole body radiation dose. The remaining 60 animals served as sham irradiated controls. The Behavioral, DTI and MRS experiments were carried out on 20 animals each at 1,3, 5, 8, 10 and 12 months (n=10 irradiated and n=10 sham) post-irradiation. All animal handling and experimental protocols were performed in strict accordance by institutional animal ethical committee. The spontaneous behavior activity and working memory in mice was evaluated using Opto-varimex 4 system and novel object recognition test. All MRS experiments were performed on anaesthetised animals (i.p., xylazine (10mg/kg BW) and ketamine (80mg/kg BW)) at 7T Bruker Biospec system. The MRS voxel was localised in the hippocampus (1.5 x 3.5 x 3.0 mm3; 15.75µl) and spectra were acquired using PRESS with TR/TE = 2500 msec/20msec and 512 averages.FID was processed using LC model for quantitation. DTI images were acquired using multi slice multi shot spin echo EPC sequence with TR/TE = 3800ms/31ms, number of gradient encoding directions = 46 and b = 672 s/mm. DTI analysis Java based software was used to generate FA and MD map and ROI was placed in left and right hippocampus for estimation of FA and MD values (Figure 1). Independent Students t test was performed to evaluate the differences among age matched control and irradiated groups.: The data for MRS, DTI and behavioural parameters were acquired at sub acute (1 month), early delayed (3, 5 and 8 months) and late delayed phases (10 and 12 months) of radiation injury. The data showed non-significant changes in behavioural as well as DTI parameters at sub acute phase of radiation injury. During early delayed phase, there was a significant decrease in cognitive index/discrimination ratio indicating impairment in hippocampal dependent recognition memory (Figure 2). However, MRS based metabolic changes, in particular myoinositol level was observed from one month post-irradiation and continued till 8 months time point (Table 1a,1b). There was no significant change observed in FA values at any time point studied but MD values were significantly decreased mainly during early delayed phase (Table 1a, 1b). At later time points (10 and 12 month post-irradiation), no profound effect of radiation exposure was seen at behavioural, metabolic and microstructural level. It indicates that whole body radiation induced changes do not persist in late delayed phase and are reversible as no significant change in cognitive function observed as compared to placebo group. In whole body radiation, changes in brain are implicated due to systemic inflammatory response, which have been observed at acute phases in our earlier studies³. Effect of systemic inflammation on microenviroment may be considered as a plausible cause for hippocampus associated changes, which may have continued till early delayed phase. However, from our findings of insignificant changes at late delayed phases, it may be presumed that with time whole body radiation induced neuroinflammation and oxidative stress may have been receded resulting in changes revering back to normal. Secondly, 5Gy of whole body radiation exposure to mice is equivalent to 2.8Gy to human, which is a moderate dose and may have a reasonable effect that may not last for long. Whole body radiation induced behavioral, metabolic and microstructual changes were observed till 8 months post-irradiation only. It is concluded from the study that whole body radiation of 5 Gy dose exposure does not have late delayed radiation injury.