The purpose of this study was to compare the language and cognitive profiles of four progressive nonfluent aphasia (PNFA) patients with 25 probable Alzheimer's disease (pAD) patients, and to identify the distinct cortical defects associated with cognitive deficits in PNFA using positron emission tomography (PET). Longitudinal observations of PNFA patients revealed progressively telegraphic speech and writing and a gradual deterioration of sentence comprehension, but memory and visual functioning were relatively preserved. Direct contrast with PAD patients revealed that PNFA patients are significantly impaired on grammatical phrase structure aspects of sentence comprehension and expression, phonemic judgments, repetition, and digit span, but not on other cognitive measures. PET studies of PNFA revealed reduced cortical activity throughout the left hemisphere. In addition, there was a prominent defect in left superior and middle temporal and inferior frontal regions of PNFA patients that differed significantly from the distribution of regional cerebral dysfunction in pAD. We conclude that PNFA is associated with a distinct profile of language and cognitive difficulty, and that this pattern of impairment is related to cortical dysfunction in a specific distribution of the left hemisphere.

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Cognitive deficits, including spatial memory impairment, are very common after ischemic stroke. Neurogenesis in the dentate gyrus (DG) contributes to forming spatial memory in the ischemic brain. Fluoxetine, a selective serotonin reuptake inhibitor, can enhance neurogenesis in the hippocampus in physiological situations and some neurological diseases. However, whether it has effects on ischemia-induced spatial cognitive impairment and hippocampal neurogenesis has not been determined. Here we report that fluoxetine treatment (10 mg kg(-1), i.p.) for 4 weeks promoted the survival of newborn cells in the ischemic hippocampus and, consequently, attenuated spatial memory impairment of mice after focal cerebral ischemia. Disrupting hippocampal neurogenesis blocked the beneficial effect of fluoxetine on ischemia-induced spatial cognitive impairment. These results suggest that chronic fluoxetine treatment benefits spatial cognitive function recovery following ischemic insult, and the improved cognitive function is associated with enhanced newborn cell survival in the hippocampus. Our results raise the possibility that fluoxetine can be used as a drug to treat poststroke spatial cognitive deficits.

The alkaloid sinomenine (7,8-didehydro-4-hydroxy-3,7-dimethoxy-17-methylmorphinan-6-one, SIN) is a bioactive alkaloid derived from the Chinese medicinal plant, Sinomenium acutum REHDER & E. H. WILSON (Family Menispermaceae). Chinese doctors have utilized this plant to treat rheumatic and arthritic diseases for over one thousand years. 1)Clinical trials done in China demonstrated that the pure alkaloid SIN had significant therapeutic effects for the patients who suffered from rheumatoid arthritis (RA). 2)RA has been classified as a chronic immune-mediated disease that exhibits overlapping manifestation of inflammatory, abnormal cellular and hormonal immune responses with synovial hyperplasia. SIN had been shown to inhibit lymphocytes proliferation in vitro 3) and improve adjuvant arthritis (AA) and antigen-induced arthritis (AIA) in rats. 4) Recently, SIN was observed inhibiting the expression of cytokines, tumor necrosis factor-alpha (TNF-a) and gamma-interferon (IFN-g), as well as the activity of nuclear factor-kappaB (NF-kB) in adjuvant arthritis (AA) rats. Furthermore SIN has suppressive effects on both Th1 and Th2 immune responses, and Th1 response is more preferentially suppressed by the SIN compared to Th2 response in mice. 5)Experimental autoimmune encephalomyelitis (EAE) is a CD4 ϩ T cell-mediated inflammatory demyelinating disease of the central nervous system (CNS) that is commonly used as a model of multiple sclerosis (MS).6) The generally accepted concept of pathogenesis in both EAE and MS involves episodes of disease onset that correlate with infiltration of activated leukocytes into the CNS, initiation of effector functions through the cytokine network, and production of histopathological lesions that result in neurological deficiencies.7) Proliferation of T cells specific for the immunizing antigen and that these antigen-specific cells produce Th1-type cytokines and transfer are believed to play a key role in this process. 8) In Lewis rats, MBP derived from guinea pig myelin is highly encephalitogenic. This is because MBP contain amino acid residues in the dominant encephalitogenic epitope for the Lewis rat, myelin basic protein (MBP) fragment 68-82 (MBP 68-82 ). MS-like immunopathology can be reproduced in Lewis rats. [9][10][11] As T cell mediated disorders including AA and EAE, some drugs such as immunoglobulins and an anti-rheumatic drug (TAK-603) protect against arthritis and EAE and that this beneficial effect is associated with a decreased proliferation of T cells specific for the immunizing antigen.12,13) For the mechanism of the anti-inflammatory and anti-rheumatic effects of SIN, we explore the effects of SIN on EAE. MATERIALS AND METHODS Experimental AnimalsFemale Lewis rats (Vital River, Beijing, China) were maintained in the SPF animal facility at Laboratory Animal Center of Nanjing Medical University under conventional conditions with laboratory chow and water accessible ad libitum. Animals were housed three or four per cage for at least 1 week prior to study. All animal procedures w...