Proximal and distant expression of growth differentiation factor 15 (GDF15) correlate with neurological deficit following experimental ischemic stroke.

BACKGROUND AND PURPOSE: Growth differentiation factor 15 (GDF15) has emerged as a promising biomarker in cerebro-cardiovascular disease, particularly in acute and chronic inflammatory stress situations. However, understanding the origins, targets and functions of GDF15 in clinical situations, such as ischemic stroke, remains a complex challenge. This study aims to assess the sources of GDF15 production following an experimental ischemic stroke. METHODS: Adult male Wistar rats underwent cerebral embolization through microspheres injection into the left or right internal carotid artery. Two hours post-surgery, GDF15 expression was analyzed in the brain, blood, lungs, liver and heart using quantitative RT-PCR and Western blotting. RESULTS: Stroke model induced large cerebral infarcts accompanied by severe neurological deficits. GDF15 gene expression exhibited a substantial increase in the ipsilateral cortex and cerebellum, with a lesser extent in the contralateral cortex. Regarding GDF15 protein expression, proGDF15 levels were elevated in the 3 aforementioned organs mentioned and the heart. However, the mature form of GDF15 was exclusively present and increased in the heart. Finally, the expression of GDF15 expression was correlated with the neurological deficit score. CONCLUSIONS: Our findings suggest that both the GDF15 gene and pro-protein are expressed in the ischemic brain after a stroke, while only its mature form is expressed remotely in in the heart. The impact of increased GDF15 in the heart following a stroke remains to be established. This is particularly relevant in understanding its relationships with poor neurological outcomes, determining whether it may contribute to stroke-induced cardiac dysfunction.

Cerebral Benefits Induced by Electrical Muscle Stimulation: Evidence from a Human and Rat Study.

Physical exercise (EX) is well established for its positive impact on brain health. However, conventional EX may not be feasible for certain individuals. In this regard, this study explores electromyostimulation (EMS) as a potential alternative for enhancing cognitive function. Conducted on both human participants and rats, the study involved two sessions of EMS applied to the quadriceps with a duration of 30 min at one-week intervals. The human subjects experienced assessments of cognition and mood, while the rats underwent histological and biochemical analyses on the prefrontal cortex, hippocampus, and quadriceps. Our findings indicated that EMS enhanced executive functions and reduced anxiety in humans. In parallel, our results from the animal studies revealed an elevation in brain-derived neurotrophic factor (BDNF), specifically in the hippocampus. Intriguingly, this increase was not associated with heightened neuronal activity or cerebral hemodynamics; instead, our data point towards a humoral interaction from muscle to brain. While no evidence of increased muscle and circulating BDNF or FNDC5/irisin pathways could be found, our data highlight lactate as a bridging signaling molecule of the muscle-brain crosstalk following EMS. In conclusion, our results suggest that EMS could be an effective alternative to conventional EX for enhancing both brain health and cognitive function.

Impact of Exercise Intensity on Cerebral BDNF Levels: Role of FNDC5/Irisin.

The positive effects of physical exercise (EX) are well known to be mediated by cerebral BDNF (brain-derived neurotrophic factor), a neurotrophin involved in learning and memory, the expression of which could be induced by circulating irisin, a peptide derived from Fibronectin type III domain-containing protein 5 (FNDC5) produced by skeletal muscle contraction. While the influence of EX modalities on cerebral BDNF expression was characterized, their effect on muscle FNDC5/Irisin expression and circulating irisin levels remains to be explored. The present study involved Wistar rats divided into four experimental groups: sedentary (SED), low- (40% of maximal aerobic speed, MAS), intermediate- (50% of MAS) and high- (70% of MAS) intensities of treadmill EX (30 min/day, 7 days). Soleus (SOL) versus gastrocnemius (GAS) FNDC5 and hippocampal BDNF expressions were evaluated by Western blotting. Additionally, muscular FNDC5/Irisin localization and serum/hippocampal irisin levels were studied by immunofluorescence and ELISA, respectively. Our findings revealed that (1) serum irisin and hippocampal BDNF levels vary with EX intensity, showing a threshold intensity at 50% of MAS; (2) hippocampal BDNF levels positively correlate with serum irisin but not with hippocampal FNDC5/Irisin; and (3) GAS, in response to EX intensity, overexpresses FNDC5/Irisin in type II muscle fibers. Altogether, peripheral FNDC5/Irisin levels likely explain EX-dependent hippocampal BDNF expression.