Patients suffering from familial hemiplegic migraine type 1 (FHM1) may have a disproportionally severe outcome after head trauma, but the underlying mechanisms are unclear. Hence, we subjected... Show morePatients suffering from familial hemiplegic migraine type 1 (FHM1) may have a disproportionally severe outcome after head trauma, but the underlying mechanisms are unclear. Hence, we subjected knock-in mice carrying the severer S218L or milder R192Q FHM1 gain-of-function missense mutation in the CACNA1A gene that encodes the alpha(1A) subunit of neuronal voltage-gated Ca(V)2.1 (P/Q-type) calcium channels and their wild-type (WT) littermates to experimental traumatic brain injury (TBI) by controlled cortical impact and investigated cortical spreading depolarizations (CSDs), lesion volume, brain edema formation, and functional outcome. After TBI, all mutant mice displayed considerably more CSDs and seizures than WT mice, while S218L mutant mice had a substantially higher mortality. Brain edema formation and the resulting increase in intracranial pressure were more pronounced in mutant mice, while only S218L mutant mice had larger lesion volumes and worse functional outcome. Here, we show that gain of Ca(V)2.1 channel function worsens histopathological and functional outcome after TBI in mice. This phenotype was associated with a higher number of CSDs, increased seizure activity, and more pronounced brain edema formation. Hence, our results suggest increased susceptibility for CSDs and seizures as potential mechanisms for bad outcome after TBI in FHM1 mutation carriers. Show less
After a reperfused myocardial infarction (MI), dynamic tissue changes occur (edema, inflammation, microvascular obstruction, hemorrhage, cardiomyocyte necrosis, and ultimately replacement by... Show moreAfter a reperfused myocardial infarction (MI), dynamic tissue changes occur (edema, inflammation, microvascular obstruction, hemorrhage, cardiomyocyte necrosis, and ultimately replacement by fibrosis). The extension and magnitude of these changes contribute to long-term prognosis after MI. Cardiac magnetic resonance (CMR) is the gold-standard technique for noninvasive myocardial tissue characterization. CMR is also the preferred methodology for the identification of potential benefits associated with new cardioprotective strategies both in experimental and clinical trials. However, there is a wide heterogeneity in CMR methodologies used in experimental and clinical trials, including time of post-MI scan, acquisition protocols, and, more importantly, selection of endpoints. There is a need for standardization of these methodologies to improve the translation into a real clinical benefit. The main objective of this scientific expert panel consensus document is to provide recommendations for CMR endpoint selection in experimental and clinical trials based on pathophysiology and its association with hard outcomes. (C) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. Show less
