ABSTRACT
Chronic cerebral hypoperfusion (CCH) causes neurodegeneration which contributes to the cognitive impairment. This study utilized a modified rat model with CCH to investigate cerebral blood flow (CBF) and hippocampal metabolic changes. CBF was measured by laser Doppler flowmetry. Various metabolic ratios were evaluated from selective volumes of interest (VOI) in left hippocampal regions using in vivo proton magnetic resonance spectroscopy ((1)H-MRS). The ultrastructural changes with special respect to ribosomes in rat hippocampal CA1 neurons were studied by electron microscopy. CBF decreased immediately after CCH and remained reduced significantly at 1 day and 3 months postoperatively. (1)H-MRS revealed that CCH led to a significant decrease of N-acetyl aspartate/creatine (NAA/Cr) ratio in the hippocampal VOI in the model rats compared with the sham-operated control rats. However, no changes of myo-inositol/Cr, choline/Cr and glutamate and glutamine/Cr ratios between the model and control groups were observed. Under electron microscopy, most rosette-shaped polyribosomes were relatively evenly distributed in the hippocampal CA1 neuronal cytoplasms of the control rats. After CCH, most ribosomes were clumped into large abnormal aggregates in the model rats. Our data suggests that both permanent decrease of CBF and reduction of NAA/Cr ratio in the hippocampal regions may be related to the cognitive deficits in rats with CCH.
Subject(s)
Aspartic Acid/analogs & derivatives , Cerebrovascular Circulation/physiology , Hippocampus/metabolism , Hypoxia-Ischemia, Brain/pathology , Hypoxia-Ischemia, Brain/physiopathology , Magnetic Resonance Spectroscopy , Animals , Aspartic Acid/metabolism , Creatine , Disease Models, Animal , Hippocampus/pathology , Hippocampus/ultrastructure , Inositol , Laser-Doppler Flowmetry , Microscopy, Electron, Transmission , Rats , Rats, Sprague-Dawley , Time Factors , TritiumABSTRACT
<p><b>OBJECTIVE</b>To investigate the feasibility of endothelial cell-targeted therapy to cure post-burn hypertrophic scar.</p><p><b>METHODS</b>A hypertrophic scar animal model was made. Intralesional injecting of VEGF monoclonal antibody was performed for three weeks. The changes of scar in volume and morphology were observed.</p><p><b>RESULTS</b>1. The volume of scar decreased. 2. The number of the capillary, the amount of collagen I and collagen III decreased. 3. Transmission electron microscope examinations demonstrated many dead or apoptotic fibroblasts and endothelial cells. Fibrocytes were seen relatively common.</p><p><b>CONCLUSION</b>VEGF induces the growth and development of hypertrophic scar in that it induces excessive and uncontrollable angiogenesis, which favors excessive collagen synthesis. Endothelial cell-targeted therapy may be a promising method to cure post-burn hypertrophic scar.</p>
