Protective effects of carnosine on white matter damage induced by chronic cerebral hypoperfusion

Carnosine is a dipeptide that scavenges free radicals, inhibits infammation in the central nervous system, and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions. Therefore, we hypothesized that carnosine would also protect against white matter damage caused by subcortical ischemic injury. White matter damage was induced by right unilateral common carotid artery occlusion in mice. The animals were treated with 200, 500 or 750 mg/kg carnosine by intraperitoneal injection 30 minutes before injury and every other day after injury. Then, 37 days later, Klfiver-Barrera staining, toluidine blue staining and immunofluorescence stain- ing were performed. Carnosine （200, 500 mg/kg） substantially reduced damage to the white matter in the corpus callosum, internal capsule and optic tract, and it rescued expression of myelin basic protein, and alleviated the loss of oligodendrocytes. However, carnosine at the higher dose of 750 mg/kg did not have the same effects as the 200 and 500 mg/kg doses. These findings show that carnosine, at a particular dose range, protects against white matter damage caused by chronic cerebral ischemia in mice, likely by reducing oligodendroglial cell loss.

Mechanism underlying the protective effect of Kaixin Jieyu Fang on vascular depression following cerebral white matter damage

The Chinese compound Kaixin fieyu Fang can be used to treat vascular depression; however, the underlying mechanism remains unclear. This study established a rat model of chronic cerebral ischemia-caused white matter damage by ligation of the bilateral common carotid arteries. Rats received daily intragastric administration of a suspension of Kaixin ]ieyu Fang powder. After 3, 7 and 21 days of treatment, the degree of white matter damage in the cerebral ischemia rat model was alleviated, Bcl-2 protein and mRNA expression in brain tissue increased, and Bax protein and mRNA expression decreased. These results indicate that Kaixin Jieyu Fang can alleviate cere- bral white matter damage, and the underlying mechanism is associated with regulation of Bcl-2/ Bax protein and mRNA expression, which is one of possible mechanism behind the protective effect of Kaixin Jieyu Fang against vascular depression.

Transmission electron microscopy of synaptic ultrastructural white matter damage in neonatal rats

BACKGROUND： To date, animal models of white matter damage remain controversial. Mild grey matter damage should be the basis for animal models to investigate white matter disease. OBJECTIVE： To establish white matter damage in neonatal rats and evaluate feasibility of the established model by observing myelination and synaptic ultrastructure. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Histology and Embryology of Guangzhou Medical College from December 2008 to May 2009. MATERIALS： H600 transmission electron microscopy was provided by Hitachi, Japan. METHODS： A total of 39 neonatal, Sprague Dawley rats were randomly assigned to normal control （n = 12）, sham-surgery （n = 12）, and white matter damage （n = 15） groups. White matter damage rats were subjected to right common carotid artery ligation, followed by inhalation of nitrogen oxygen gas mixture （6% oxygen） for 4 hours. MAIN OUTCOME MEASURES： Myelin sheath and synaptic ultrastructure in the injured （right） hippocampal CA1 region in 1-month-old rats were observed through the use of transmission electron microscopy, and pathological changes in the cerebral cortex and corpus callosum of the right hemisphere were detected by hematoxylin-eosin staining. RESULTS： Obvious tissue loss was observed in the corpus callosum of the injured （right） hemisphere. Injured oligodendrocytes and disrupted myelination were observed in the white matter damage group. However, synaptic length in the active zones, width of synaptic cleft, thickness of postsynaptic density, and curvature of the synaptic interface remained unchanged following injury, compared with the control and sham-surgery groups （P 〉 0.05）. CONCLUSION： The established white matter damage model resulted in changes in myelination and slightly altered synaptic ultrastructures. The model could function as an ideal model for white matter damage in neonatal rats.

Strategies for myelin regeneration: lessons learned from development

Myelin regeneration is indispensably important for patients suffering from several central nervous system （CNS） disorders such as multiple sclerosis （MS） and spinal cord injury （SCI）, because it is not only essential for restoring neurophysiology, but also protects denuded axons for secondary degeneration. Understanding the cellular and molecular mechanisms underlying remyelination is critical for the development of remyelination-specific therapeutic approaches. As remyelination shares certain common mechanisms with developmental myelination, knowledge from study of developmental myelination contributes greatly to emerging myelin regeneration therapies, best evidenced as the recently developed human anti-Nogo receptor interacting protein-1 （LINGO-1） monoclonal antibodies to treat MS patients in clinical trials.

Protection of Effective Component Group from Xiaoshuan Tongluo on Brain Injury after Chronic Hypoperfusion in Rats

Objective To investigate the protective effects of purified effective component group in extract from Xiaoshuan Tongluo(CGXT) formula on chronic brain ischemia in rats.Methods CGXT 75,150,and 300 mg/kg or vehicle were ig administered daily for four weeks to rats with bilateral common carotid arteries ligation(BCCAL) .From the day 24 to 28 after BCCAL,Morris water maze was performed to assess the learning and memory impairment of rats.Four weeks after BCCAL,brain gray and white matter damage were assessed.Results In Morris test,the mean escape latency of rats in the CGXT(150 and 300 mg/kg) groups was significantly shorter than that in the vehicle group.CGXT also attenuated the neuronal damage in hippocampus and cortex and reduced the pathological damage in the optic tract and corpus callosum.Conclusion CGXT could improve learning and memory impairment resulted from BCCAL in rats.These results provide the experimental basis for the clinical use of CGXT in stroke treatment and may help in investigation of multimodal therapy strategies in ischemic cerebrovascular diseases including stroke.