Abstract TP112: Post-conditioning with Isoflurane Reduces Ischemia-induced Hemorrhage and Brain Injury Following MCAO in Rats: A Longitudinal Study with MRI

Abstract

The objective of this study was to use multimodal MR imaging to evaluate the effect of isoflurane on short-term and long-term neuronal tissue damage and neurological deficits after focal brain ischemia in rats and correlate the improvement with the behavioral outcome. Male Wistar/Kyoto rats were divided into 4 experimental groups; Control (Group I, n=5), Sham (Group II, n=5), MCAO (Group III, n=20) and MCAO with isoflurane treatment (Group IV, n=20). Animals were anesthetized with 5% isoflurane and maintained on 2% isoflurane during surgery. MCA was transiently occluded (90 min) using intra-luminal thread. After surgery, group IV was kept under 2% isoflurane for 90 min period. Other groups were allowed to recover immediately after the surgery. Animals were subjected to MRI to measure, infract volume, edema and blood flow in 8 in vivo imaging sessions performed at 6, 12, 24, 48, 72h (short term) and 7, 14 and 21d (long term) post MCAO. Anatomical, diffusion and arterial spin labeling (ASL) were performed with 7T MR Scanner. The following parameters were used in DTI; TE/TR=23/5000 ms, diffusion directions 30, b=100, 850, and 1850 s/mm2, FOV 4.0 x 4.0 cm, 12 slices with thickness 1 mm, and matrix 128 x 128. Standard ASL sequence was used to calculate the regional blood flow. Diffusion images were processed to generate diffusion parameter maps. Mean diffusion parameters calculated in the infarct regions were manually drawn on T2 maps. Behavioral improvement was measured in terms of latency on rotarod and beam walk. Rats post-conditioned with isoflurane did not show hemorrhage during short term or long term post MCAO, while non-conditioned rat develop hemorrhage after short term post MCAO. Lesion in the cortical area was noticed since 6h post MCAO. However, cortical lesion was significantly reduced in the treatment group. Post-conditioned rats had significantly higher latency on rotarod and lesser number of foot faults on beam walk test measured on day 3,7,14 and 21 of MCAO, implying isoflurane mediated functional protection. Our results for the first time, at the longitudinal level show that maintaining MCAO rats under isoflurane environment before reperfusion offers enhanced neuroprotection and recovery from behavioral dysfunction through reduced brain hemorrhage.