摘要:

We have previously reported a larger and more prolonged increase of slow wave activity (SWA) in NREM sleep after sleep deprivation (SD) in prion protein deficient mice (PrP) compared to wild-type mice. Regional differences in the SWA increase were investigated by comparing the effect of 6 h SD on a frontal and occipital derivation in PrP deficient mice and wild-type mice. The larger increase of SWA after SD in PrP deficient mice was restricted to the occipital derivation. The difference appeared after the waking–NREM sleep transitions, making it unlikely that PrP is involved in the mechanisms enabling the transition to sleep. Our findings may reflect differences between the genotypes in the need for recovery in this particular brain region.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The immature brain is more prone to seizures than the older brain as a result of an imbalance between excitatory and inhibitory input. The depolarizing, rather than hyperpolarizing effect of GABAAduring the first week of life in the rodent, and the delay in post-synaptic GABABinhibition coupled with the over-expression of glutamatergic synapses contribute to this increased propensity toward seizures. It is now clear that seizures can be injurious to the immature brain, although the pattern of seizure-induced injury is age-related. While the immature brain is resistant to acute seizure-induced cell loss, there are functional abnormalities following seizures with impairment of visual-spatial memory and reduced seizure threshold. Neonatal seizures are also associated with a number of activity-dependent changes in brain development including altered synaptogenesis and reduction in neurogenesis. These results argue that neonatal seizures should no longer be considered as benign events.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

We have examined the effects of serotonin2(5-HT2) stimulation and NMDA antagonism on preprotachykinin (PPT) and preproenkephalin (PPE) gene regulation in the dopamine (DA) depleted striatum. Following DA lesions, PPT mRNA expression was reduced (dorsomedial (DM) 44±9%, dorsolateral (DL) 40±4%), whereas PPE message levels were elevated (DM 207±28%, DL 198±25%). Within this state of dysregulated gene activity, DOI (5-HT2agonist) increased PPT message levels (174±5%, DM; 153+13%, DL) without affecting PPE gene expression. In addition, MK-801 (NMDA antagonist) decreased PPE message levels (DM 59±10%, DL 52±7%) without significantly altering PPT mRNA expression. Combined application of DOI and MK-801 resulted in normalization of both PPT and PPE message. Statistical analysis revealed no drug interactions in this paradigm suggesting independent mechanisms for 5-HT2and NMDA receptors in controlling neuropeptide production following DA depletion.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Different diseases of the CNS are associated with blood–brain barrier (BBB) damage and mononuclear cell infiltration. In order to study genes that may play a role in endothelial cell regulation in inflammatory CNS diseases, we performed differential gene expression (DGE) analysis using a mouse brain endothelial cell line. We found that interferon-γ (IFNγ)-induced monokine (MIG), a chemokine that plays a role in T lymphocyte and monocyte chemoattraction, is highly expressed in the presence of inflammatory cytokines.We show that MIG, produced by brain endothelial cellsin vitro, is biologically active in attracting T lymphocytes and that it is possible to interfere with this mechanism of action using anti-MIG antibodies. We suggest that blocking MIG may be beneficial in CNS inflammation. We detected constitutive expression of the MIG receptor, CXCR3, on the surface of the endothelial cells and therefore hypothesize that it plays a role in maintaining the cytokine gradient at the region of CNS inflammation.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The human amygdala's involvement in negative emotion is well established, but relatively little is known regarding its role in positive emotion. Here we examined the neural response to emotionally positive, negative, and neutral words using fMRI. Relative to neutral words, positive and negative emotional words elicited greater activity in the left amygdala. Positive but not negative words elicited activity in dorsal and ventral striatal regions which have been linked in previous neuroimaging studies to reward and positive affect, including caudate, putamen, globus pallidus, and accumbens. These findings provide the first direct evidence that the amygdala is involved in emotional reactions elicited by both positive and negative emotional words, and further indicate that positive words additionally activate brain regions related to reward.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Platelet-activating factor (PAF) is a pro-inflammatory molecule which contributes to secondary damage after spinal cord injury (SCI). To test if PAF contributes to cytokine induction following SCI, female Long-Evans rats were pretreated with the PAF antagonist WEB 2170 prior to receiving a contusion injury at spinal cord level T10 using the NYU impactor. RNase protection assay (RPA) analysis revealed that IL-1α mRNA peaked at 1 h post-injury while IL-1β and IL-6 mRNA levels were higher and peaked at 6 h. TNF-α mRNA was almost undetectable. All mRNA levels approached baseline by 24 h. Treatment with WEB 2170 (1 mg/kg, i.p.) 15 min prior to injury significantly decreased mRNA levels for all three cytokines at 6 h post-injury, but not at 1 h post-injury. These results demonstrate a role for PAF in proinflammatory cytokine induction after SCI.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

In earlier studies the dihydroxylated tetrahydroisoquinoline derivatives salsolinol and 2(N)-methyl-norsalsolinol (NMNorsal), a 2(N)-analogue of salsolinol, were identified as putative endogenous neurotoxins in patients with Parkinson's disease. Since a prominent blood–brain barrier (BBB) was described to exist for salsolinol, in the present study microdialysis experiments were performed to investigate the penetration of NMNorsal through the BBB into the caudate nucleus of the rat brain. After i.p. administration of NMNorsal (20 mg/kg), it could be detected in the dialysate of the caudate nucleus with a mean maximum after 40 min. There was no alteration in extracellular dopamine or 3,4-dihydroxyphenylacetic acid levels. Addition of the monoamine oxidase inhibitor pargyline (10 μM) to the perfusate did not modify NMNorsal levels in the caudate nucleus. To corroborate the microdialysis results, homogenates of the contralateral caudate nucleus were prepared and NMNorsal could also be detected. These findings indicate that NMNorsal is indeed able to pass through the blood–brain barrier of the rat brain.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Huntington's Disease (HD) is a serious dominantly inherited neurodegenerative disorder for which there are no current treatments. Open label and animal studies have suggested that highly unsaturated fatty acids (HUFAs) may be beneficial. Seventeen patients with HD were entered into a randomised, placebo-controlled, double blind trial of HUFA therapy. Patients were assessed on the Rockland-Simpson Dyskinesia Rating Scale (RSDRS) and the Unified Huntington's Disease Rating Scale (UHDRS). On the RSDRS and the UHDRs motor scale patients on HUFA treatment improved while those on placebo deteriorated, with a significant difference between the two groups on the RSDRS. A similar trend was noted on the UHDRS functional performance scales. Little change was seen on the neuropsychology scales. There were no treatment-related adverse events. This is the first time that a significant improvement has been noted in a randomised trial in HD. The results are consistent with open label observations; a second placebo-controlled study in end-stage patients, and a study in a transgenic mouse model of HD.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Resident microglial cells contribute to activation and expansion of T cells under inflammatory conditions within the CNS. However, there is no evidence how interactions between microglia and T cells affect CNS inflammation. We evaluated the effect of glial cell-derived dendritic cells (GC-DC) in expanding and eliminating myelin basic protein (MBP)-reactive T cells. GC-DC untreated with TGF-β1 (GC-DC0) primed antigen specific T cell proliferation, whereas GC-DC treated with TGF-β1 (GC-DCβ) effectively inhibited expansion of T cells via inducing IFN-γ-expressing CD8+T cells. Augmented IFN-γ and/or TNF-α might also affect the elimination of MBP-reactive T cells. These results indicate that TGF-β1-mediated functional skewing of GC-DC plays a critical role for the elimination of MBP-reactive T cells.

ISSN:0959-4965    

出版商:OVID    

年代:2002

数据来源: OVID