Microglial inhibitory factor (MIF/TKP) mitigates secondary damage following spinal cord injury

Spinal cord injury (SCI) induces an immune response during which microglia, the resident immunocompetent cells of the central nervous system, become activated and migrate to the site of damage. Depending on their state of activation, microglia secrete neurotoxic or neurotrophic factors that influence the surrounding environment and have a detrimental or restorative effect following SCI, including causing or protecting bystander damage to nearby undamaged tissue. Subsequent infiltration of macrophages contributes to the SCI outcome. We show here that suppressing microglia/macrophage activation using the tripeptide macrophage/microglia inhibitory factor (MIF/TKP) reduced secondary injury around the lesion epicenter in the murine dorsal hemisection model of SCI; it decreased the hypertrophic change of astrocytes and caused an increase in the number of axons present within the lesion epicenter. Moreover, timely inhibition of microglial/macrophage activation prevented demyelination and axonal dieback by modulating oligodendrocyte survival and oligodendrocyte precursor maturation. Microglia/macrophages located within or proximal to the lesion produced neurotoxic factors, such as tumor necrosis factor alpha (TNF-α). These results suggest that microglia/macrophages within the epicenter at early time points post injury are neurotoxic, contributing to demyelination and axonal degeneration and that MIF/TKP could be used in combination with other therapies to promote functional recovery.     

Cognitive impairment and dementia in Parkinson's disease

Relatively subtle cognitive disturbances may be present from the initial stages of Parkinson's disease (PD) that progress in many patients to a more severe cognitive impairment and dementia. Several of the initial deficits are ascribed to failure in the frontal-striatal basal ganglia circuits and involve executive defects in planning, initiation, monitoring of goal-directed behaviors and working-memory. Other non-demented PD patients also exhibit visuospatial and memory deficits more representative of posterior cortical functioning and fail performing naming or copying tasks. Major differences in the overall rate of cognitive decline among PD patients support the co-existence of at least two patterns of involution, differentiating a relatively slow decline of fronto-striatal deficits from a more rapid decline of posterior-cortical deficits, with different pathophysiological substrates, genetics, prognosis and response to drugs used to treat the motor symptoms of PD.     

Seeing with the eyes shut: Neural basis of enhanced imagery following ayahuasca ingestion

The hallucinogenic brew Ayahuasca, a rich source of serotonergic agonists and reuptake inhibitors, has been used for ages by Amazonian populations during religious ceremonies. Among all perceptual changes induced by Ayahuasca, the most remarkable are vivid “seeings.” During such seeings, users report potent imagery. Using functional magnetic resonance imaging during a closed‐eyes imagery task, we found that Ayahuasca produces a robust increase in the activation of several occipital, temporal, and frontal areas. In the primary visual area, the effect was comparable in magnitude to the activation levels of natural image with the eyes open. Importantly, this effect was specifically correlated with the occurrence of individual perceptual changes measured by psychiatric scales. The activity of cortical areas BA30 and BA37, known to be involved with episodic memory and the processing of contextual associations, was also potentiated by Ayahuasca intake during imagery. Finally, we detected a positive modulation by Ayahuasca of BA 10, a frontal area involved with intentional prospective imagination, working memory and the processing of information from internal sources. Therefore, our results indicate that Ayahuasca seeings stem from the activation of an extensive network generally involved with vision, memory, and intention. By boosting the intensity of recalled images to the same level of natural image, Ayahuasca lends a status of reality to inner experiences. It is therefore understandable why Ayahuasca was culturally selected over many centuries by rain forest shamans to facilitate mystical revelations of visual nature. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Validation of the Subjective Handicap of Epilepsy (SHE) in Brazilian patients with epilepsy

The objectives of the study were to translate and adapt the Subjective Handicap of Epilepsy (SHE) instrument to Brazilian Portuguese and to determine its psychometric properties for the evaluation of quality of life in patients with epilepsy. A sample of 448 adult patients with epilepsy with different clinical profiles (investigation, preoperative period, postoperative period, and drug treatment follow-up) was evaluated with the SHE and the Epilepsy Surgery Inventory (ESI-55). Exploratory factorial analysis demonstrated that four factors explained 60.47% of the variance and were sensitive to discriminate the different clinical groups, with the preoperative group having the poorest quality of life. Internal consistency ranged from 0.92 to 0.96, and concurrent validity with the ESI-55 was moderate/strong (0.32-0.70). Test-retest reliability was confirmed, with an ICC value of 0.54 (2 days), 0.91 (7 days), and 0.97 (30 days). The SHE had satisfactory psychometric qualities for use in the Brazilian population, similar to those of the original version. The instrument seems to be more adequate in psychometric terms for the postoperative and drug treatment follow-up groups, and its use should be encouraged.     

Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines

Mild cognitive impairment is common in nondemented Parkinson's disease (PD) patients and may be a harbinger of dementia. In view of its importance, the Movement Disorder Society commissioned a task force to delineate diagnostic criteria for mild cognitive impairment in PD. The proposed diagnostic criteria are based on a literature review and expert consensus. This article provides guidelines to characterize the clinical syndrome and methods for its diagnosis. The criteria will require validation, and possibly refinement, as additional research improves our understanding of the epidemiology, presentation, neurobiology, assessment, and long-term course of this clinical syndrome. These diagnostic criteria will support future research efforts to identify at the earliest stage those PD patients at increased risk of progressive cognitive decline and dementia who may benefit from clinical interventions at a predementia stage.