| Objective To observe short/long-dated damage on hippocampus in rats with different plasma concentration hyperbilirubinemia, reevaluate the dangerous degree of hyperbilirubinemia according to the results of growth associated protein-43 (GAP-43) expressed, neuron Nissl body counted, Morris water maze tested and the long-term potential (LTP) changed in vivo,and investigate the protective effects of basic fibroblast growth factor (bFGF) in order to provide references for clinical treatment on hyperbilirubinemia.Methods (1) Seventy five rats were divided randomly into four groups:Control group (CG), test-1 group (T1G), test-2 group (T2G), BFGF treated group (BTG).(2) Hyperbilirubinemia models were established by injecting confected liquid of bilirubin into 7d old rats' abdominal cavity.Judging the success of models by measuring the bilirubin concentrations in plasma/brains and observing the macro-/ micro-morphological features of brains.(3) The bFGF was used in BTG at 30min, 1d, 3d, 5d and 7d respectively after operation of bilirubin. GAP-43 expression and amount of Nissl body were measured at 2d, 8d, 28d and 60d to evaluate the microcosmic neurotoxicity of bilirubin. The ultrastructure changes of brain were observed with electromicroscope. (4) When part of model rats were feed to 60d old in separate cages, the LTP in hippocampus and tests of Morris water maze were detected to explore the long-dated damages of hyperbilirubinemia on learning and memory. Therapeutic effects of bFGF on hyperbilirubinemia were evaluated by the same methods. Results (1) The model groups displayed the steady and significant abnormalities of emotion and behaviors, and concentrations of plasma and brain tissue of T1G and T2G were far higher than that of CG. Bilirubin deposits were only found in brains of T2G. (2) The expression of GAP-43 of all groups showed the same tendency: the highest level appeared on 8d and the lowest level on 60d. Compared to CG, the data of T1G and T2G were more significantly higher (P<0.05 and P<0.01 respectively), and degree of T2G was more remarkable. (3) Amount of Nissl body decreased in model groups, and phenomenon of light-colored and anomalistic form were here and there. Neuronophagia phenomenon could be found in T2G.(4) Slices of electromicroscope represented significantly changes in morphologic: edema of nerve fibers, abnormity of organelles and hyperplastic glia cells were prevalent. Deposit of lipofuscin in neurons, which was usually regarded as the signal of cell senescence was never been reported in former assy literatures about analogous tests.(5) Morris water maze: In the place navigation test (PNT) and the spatial probe test (SPT), we observed the average escape latency (EL) delayed, which indicated capability of spatial learning of model groups suffered from hyperbilirubinemia, but memory of T1G was still normal, contrary to what T2G represented. (6) Compared to the CG, field potential recorded in hippocampus of model groups showed great decreasing change rates of PS at the same points (p<0.05), and significant differences were found. (7) BFGF could enhance the expression level of GAP-43 and amount of Nissl body, improve almost all the negative changes from hyperbilirubinemia. In the Morris water maze, the treated group showed shorter EL, more accurate capability of judging orientation and better memory.In the LTP, change rate of PS at the same points rised by 13.9, difference in statistics was remarkable(P<0.05).(8) The improvements from bFGF were certain but not enough for eliminating the difference completely between CG and treated group. Conclusion (1) Neurotoxicity of bilirubin is certain, and the damage occurs by killing the neurons or blocking communication among neural fibers or disordering stability of memory for received information. (2) Nerve system of organism could react to stimulations form environment, try to make up succedent damage by enhancing level of some endogenetic substance, and advance the regeneration at the same time. But these...
|
PDF Full Text Request