Neurodevelopmental Effects of Prenatal Cannabidiol Exposure on the Offspring of Rats in the Postnatal Period

Cannabis use during pregnancy has recently increased worldwide. Cannabidiol (CBD), the main non-intoxicating compound in Cannabis, is often seen as a natural substance and has been used for the treatment of several health conditions. During pregnancy, women might choose to use CBD to treat very common pregnancy-related symptoms, such as nausea and vomiting. However, there is very little evidence regarding the safety of CBD use during pregnancy and the possible outcomes to maternal and fetal health. In this context, we tested the effects of prenatal CBD exposure on pregnancy outcomes, offspring physical health and neurodevelopment. Pregnant rats were treated by intraperitoneal injection with either a drug vehicle solution (1:1:18 ethanol:kolliphor:PBS), 5 mg/kg CBD or 10 mg/kg CBD during gestational days 6 to 20. Offspring physical health was assessed until weaning on post-natal day (PND) 21. Different neurodevelopmental tests were conducted from PND3 to PND21 to measure the development of neurological reflexes and postural mechanisms. Prenatal CBD exposure was associated with a lower body weight in offspring and a delay in the development of reflexes in early stages after birth. These findings contribute to the current evidence available on the consequences of in utero CBD exposure and brings light to the need for further research in the area

A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility

We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10−40, OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1∗04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10−43) and HLA-DQα1 47 (p = 4.02 × 10−46), 56, and 76 (both p = 1.84 × 10−45) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10−6, OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10−6, OR = 1.20), and REL (rs115674477, p = 1.10 × 10−5, OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function

Microcirculatory Changes in Experimental Models of Stroke and CNS-Injury Induced Immunodepression

Stroke is the second-leading cause of death globally and the leading cause of disability in adults. Medical complications after stroke, especially infections such as pneumonia, are the leading cause of death in stroke survivors. Systemic immunodepression is considered to contribute to increased susceptibility to infections after stroke. Different experimental models have contributed significantly to the current knowledge of stroke pathophysiology and its consequences. Each model causes different changes in the cerebral microcirculation and local inflammatory responses after ischemia. The vast majority of studies which focused on the peripheral immune response to stroke employed the middle cerebral artery occlusion method. We review various experimental stroke models with regard to microcirculatory changes and discuss the impact on local and peripheral immune response for studies of CNS-injury (central nervous system injury) induced immunodepression

The calcium release complex in skeletal muscle and its associated diseases

International audienceIntroduction The coupling between the stimulation of a muscle fibre and the massive intracellular calcium release, that is the molecular basis of muscle contraction, is fulfilled by a macromolecular complex, the calcium release complex (CRC). Exegesis A very precise molecular architecture is required for CRC correct function, as well as a specific membrane organisation in muscle cells. Conclusion Several muscle pathologies are associated with mutations in the two calcium channels of the CRC. However, elucidation of mechanisms involved in CRC function are still required to characterise muscle pathologies of unknown origin