PPARα Agonist Fenofibrate Ameliorates Learning and Memory Deficits in Rats Following Global Cerebral Ischemia.

Increasing evidence demonstrates that local inflammation contributes to neuronal death following cerebral ischemia. Peroxisome proliferator-activated receptor α (PPARα) activation has been reported to exhibit many pharmacological effects including anti-inflammatory functions. The aim of this study was to investigate the neuroprotective effects of PPARα agonist fenofibrate on the behavioral dysfunction induced by global cerebral ischemia/reperfusion (GCI/R) injury in rats. The present study showed that fenofibrate treatment significantly reduced hippocampal neuronal death, and improved memory impairment and hippocampal neurogenesis after GCI/R. Fenofibrate administration also inhibited GCI/R-induced over-activation of microglia but not astrocytes and prevented up-regulations of pro-inflammatory mediators in hippocampus. Further study demonstrated that treatment with fenofibrate suppressed GCI/R-induced activations of P65 NF-κB and P38 MAPK. Our data suggest that the PPARα agonist fenofibrate can exert functional recovery of memory deficits and neuroprotective effect against GCI/R in rats via triggering of neurogenesis and anti-inflammatory effect mediated by inhibiting activation of P65 NF-κB and P38 MAPK in the hippocampus, which can contribute to improvement in neurological deficits.

Valproic acid alleviates memory deficits and attenuates amyloid-ß deposition in transgenic mouse model of Alzheimer's disease.

In the brains of patients with Alzheimer's disease (AD) and transgenic AD mouse models, astrocytes and microglia activated by amyloid-ß (Aß) contribute to the inflammatory process that develops around injury in the brain. Valproic acid (VPA) has been shown to have anti-inflammatory function. The present study intended to explore the therapeutic effect of VPA on the neuropathology and memory deficits in APPswe/PS1ΔE9 (APP/PS1) transgenic mice. Here, we report that VPA-treated APP/PS1 mice markedly improved memory deficits and decreased Aß deposition compared with the vehicle-treated APP/PS1 mice. Moreover, the extensive astrogliosis and microgliosis as well as the increased expression in interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the hippocampus and cortex of APP/PS1 transgenic mice were significantly reduced following administration of VPA, which attenuated neuronal degeneration. Concomitantly, VPA alleviated the levels of p65 NF-κB phosphorylation and enhanced the levels of acetyl-H3, Bcl-2, and phospho-glycogen synthase kinase (GSK)-3ß that occurred in the hippocampus of APP/PS1 transgenic mice. These results demonstrate that VPA could significantly ameliorate spatial memory impairment and Aß deposition at least in part via the inhibition of inflammation, suggesting that administration of VPA could provide a therapeutic approach for AD.

WITHDRAWN: Transplantation of bone mesenchymal stem cells containing the nerve growth factor gene in adult rat brain with Fimbria Fornix lesion.

Bone marrow-derived mesenchymal stem cells (BMSCs) are a promising source for cell-based treatment of brain injury, but the therapy of BMSCs is restricted by low cell survival. We examined whether nerve growth factor (NGF) improve BMSCs viability in the brain with Fimbria-Fornix lesion (FF). After transduction of NGF gene via recombinant retroviral vectors, the rat BMSCs were transformed into the NGF-GFP positive BMSCs, nearly 100% of cells expressed NGF. After transplanted into basal forebrain of rat with FF, the NGF-GFP positive BMSCs expressed the exogenous NGF gene in the host brain, and interesting, the survival number of BMSCs in the NGF group was significant more than that of the void plasmid group. Furthermore, the number of choline acetyltransferase (ChAT) immunoreactive neurons of NGF group was also significant higher than those of the void plasmid group (p<0.05) or the PBS group (p<0.01). Performance in the water maze test was improved in these rats in NGF group. These results indicate that NGF increased BMSCs survival in brain with FF, which results in better improvement of brain function than injected with BMSCs alone.

[Damaging nucleus centromedianus thalami for treatment of cancer pain in experimental and clinical aspects].

BACKGROUND & OBJECTIVE: There is no perfect method to control cancer pain. It is reported that nucleus centromedianus thalami plays a crucial role in the analgesia of central nerve system. The authors conducted this study, based on rat experiments, together with the clinical treatment of more than 90 cases involving various cancer pains, to explore the pain-relieving effects after damaging nucleus centromedianus thalami. METHODS: Ten SD rats, whose nucleus centromedianus thalami were damaged by electrolysis, were chosen, and then measured the pain degree by applying electricity to stimulate the tails of the rats. Meanwhile, another 10 rats, whose nucleus centromedianus thalami were not damaged, were chosen as the control group, among whom the same operation procedure as the above mentioned was carried out. The range of pain scale of the rats was measured by the alteration of the electric intensity. A total of 90 cases of intractable cancer pain were treated, including 36 cases of lung cancer, 21 cases of nasopharyngeal carcinoma, 10 cases of intestinal cancer, 8 cases of cancer of pancreas, 8 cases of osteocarcinoma, 4 cases of carcinoma of kidney, 3 cases of hepatocarcinoma. The brain stereotactic technique was used to damage the nucleus centromedianus thalami with radiofrequency coagulation lesions. The 10-grade method recommended by WHO was used to rank pain degree. RESULTS: Pain scale of rats in the first group rose from 0.152+/-0.034 mA prior to the damage to 0.326+/-0.05 afterwards, with a significant difference (P< 0.001), while the pain scale of the control group dropped from 0.142+/-0.027 mA prior to the operation to 0.138+/-0.035 mA afterwards, with no remarkable difference (P > 0.05). To patients with cancer pain, the average pain grade in this study went above 7 scores, but dropped to 0-3 scores after operation, according to the 10 grade method by WHO. A life-long tracing observation indicted that cancer pain in 24 cases relapsed to varying degrees but below 5 scores, the rest of the patients were analgesic persistently, 3 cases among whom lasted for as long as 2 years. The incidence cases of operational complications were 15 of somnolence, 10 of urinary incontinence, 8 of divagation, and 3 of unilateral oculomotor paralysis. These complications released after symptomatic treatments. CONCLUSION: Nucleus centromedianus thalami damage is an effective way to relieve cancer pain, as well as the complications should be paid attention.