Monitoring microvascular perfusion variations with laser speckle contrast imaging using a view-based temporal template method

Purpose Laser speckle contrast imaging (LSCI) continues to gain an increased interest in clinical and research studies to monitor microvascular perfusion. Due to its high spatial and temporal resolutions, LSCI may lead to a large amount of data. The analysis of such data, as well as the determination of the regions where the perfusion varies, can become a lengthy and tedious task. We propose here to analyze if a view-based temporal template method, the motion history image (MHI) algorithm, may be of use in detecting the perfusion variations locations. Methods LSCI data recorded during three different kinds of perfusion variations are considered: (i) cerebral blood flow during spreading depolarization (SD) in a mouse; (ii) cerebral blood flow during SD in a rat; (iii) cerebral blood flow during cardiac arrest in a rat. Each of these recordings was processed with MHI. Results We show that, for the three pathophysiological situations, MHI identifies the area in which perfusion evolves with time. The results are more easily obtained compared with a visual inspection of all of the frames constituting the recordings. MHI also has the advantage of relying on a rather simple algorithm. Conclusions MHI can be tested in clinical and research studies to aid the user in perfusion analyses

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission. © 2019, The Author(s)

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission. © 2019, The Author(s)