Brain Physiology Lab

Irisin, a myokine cleaved from its precursor FNDC5 (fibronectin type III domain-containing protein 5) following exercise or low-frequency whole-body vibration, regulates energy metabolism and insulin sensitivity. This study examines irisin's therapeutic potential in stroke in rats. Adult Sprague-Dawley rats of both sexes underwent transient middle cerebral artery occlusion (90 minutes) or sham surgery. After 4.5 hours, they were randomized to receive saline or irisin treatment (0.1, 0.2, and 0.8 μg/g body weight). Infarct volume was quantified 1 day after transient middle cerebral artery occlusion using 2,3,5-triphenyltetrazolium chloride staining. In a subsequent study, reproductively senescent female rats received either saline or 0.2 μg/g body weight irisin at 4.5 hours post-transient middle cerebral artery occlusion, followed by weekly treatments for a month. Sensorimotor and cognitive functions were assessed using the cylinder test and Morris water maze. Ipsilateral cortical tissue was collected from a subset of the reproductive senescence rats following 2 weeks of treatment for RNA sequencing and real-time quantitative polymerase chain reaction analysis. Irisin (0.2 μg/g) significantly reduced infarct volume by 50% in females and 36% in males compared with their respective saline groups. In reproductive senescence females, irisin treatment for a month improved contralateral limb use by day 7 and enhanced spatial learning in the Morris water maze, reducing latency to find the hidden platform on the fourth day of testing (16.5 sec versus saline; P<0.05) and increasing time spent in the target quadrant during the probe trial (9.3 sec versus saline; P<0.05). Irisin therapy significantly altered cortical gene expression, with 332 genes upregulated and 136 downregulated. Gene ontology analysis revealed genes linked to the extracellular matrix were significantly upregulated, which was confirmed by increased expression of the cell-surface integrin αVβ5, known to interact with irisin. Post-transient middle cerebral artery occlusionirisin therapy modulates the transcriptome, enhancing motor and cognitive function while protecting against ischemic brain damage in middle-aged female rats.

Functional and morphological alterations of islet capillaries occur in mice early after multiple low dose STZ treatment;Islet pericytes remodel and express higher levels of the myofibroblast marker periostin upon STZ treatment; Islet pericyte cytosolic Ca 2+ and vasomotor responses to high glucose are impaired in living pancreas slices from mice treated with STZ; Islet hyperemic responses to increases in glycemia recorded in the exteriorized pancreas are abolished in STZ-treated mice;Vascular alterations are associated with a pro-inflammatory environment as islets from STZ-treated mice have more macrophages, an inflamed and leaky endothelium.

The previously observed heterogeneity in developmental and intergenerational trajectories of childhood trauma may root from interindividual differences in the way trauma-exposed individuals have resolved these experiences. The current study explored whether distinctive patterns of impaired mentalization in relation to trauma could be identified in a sample of 825 pregnant women who experienced childhood maltreatment and whether these heterogeneous patterns were marked by significant differences in internalized and externalized problems during pregnancy, intimate partner violence, personality dysfunctions, and antenatal attachment. A latent profile analysis applied to the seven subscales of the Failure to Mentalize Trauma Questionnaire unraveled interindividual variability in mentalizing impairments among pregnant women exposed to childhood maltreatment by identifying five distinctive types of psychological responses to trauma, each being associated in cross-sectional analyses with a specific set of symptoms and dysfunctions. Overall, the study highlights the need for tailored interventions based on the individuals' specific impairments in mentalizing trauma and calls for future developmental research exploring the longitudinal correlates of the five documented profiles of trauma processing.

O acidente vascular cerebral corresponde à principal causa de morbimortalidade no Brasil. Com o intuito de reduzir a extensão do comprometimento funcional, a modulação da neuroplasticidade, através da estimulação cerebral profunda (ECP), emerge-se como potencial alvo terapêutico. A despeito de fármacos sistêmicos, a ECP independe do fluxo sanguíneo e do estado da barreira hematoencefálica, bem como evita a exposição química de outros órgãos, sendo explorada especialmente no acidente vascular cerebral isquêmico (AVCi).