Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage

About 50% of humans with aneurysmal subarachnoid hemorrhage (SAH) die and many survivors have neurological and neurobehavioral dysfunction. Animal studies usually focused on cerebral vasospasm and sometimes neuronal injury. The difference in endpoints may contribute to lack of translation of treatments effective in animals to humans. We reviewed prior animal studies of SAH to determine what neurological and neurobehavioral endpoints had been used, whether they differentiated between appropriate controls and animals with SAH, whether treatment effects were reported and whether they correlated with vasospasm. Only a few studies in rats examined learning and memory. It is concluded that more studies are needed to fully characterize neurobehavioral performance in animals with SAH and assess effects of treatment

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Temperature Dependence of Bandgap in Lead‐Halide Perovskites with Corner‐Sharing Octahedra

Understanding the molecular origin of the atypical temperature dependence of bandgap (i.e., bandgap renormalization) in lead‐halide perovskites with corner‐sharing octahedra is of fundamental interest and a prerequisite for their applications in fabricating high‐performance optoelectronic devices. The bandgap renormalization is attributed to the lattice thermal expansion and electron–phonon interactions. However, it remains controversial whether the thermal expansion has a negligible effect on the band‐edge structure of corner‐sharing [PbX6]4− (X = halide anion) octahedra in perovskites, relative to the electron–phonon interactions. In this review, this issue is clarified by focusing upon the most recent theoretical advances in the field of investigating the bandgap renormalization in perovskites. The timely research progress on the modulation of bandgap renormalization through the structural engineering in perovskites is also outlined. Finally, a vision about the directions for further in‐depth research in this field is provided, with the intent of promoting a more profound understanding and controlling of bandgap renormalization in perovskites in the future

Identification of key genes associated with multiple sclerosis based on gene expression data from peripheral blood mononuclear cells

The aim of this study was to identify the potential key candidate genes of multiple sclerosis (MS) and uncover mechanisms in MS. We combined data from the microarray expression profile of three MS stages and performed bioinformatics analysis. Differentially expressed genes (DEGs) were identified among the distinct stages of MS and healthy controls, and a total of 349 shared DEGs were identified. Gene ontology (GO) and pathway enrichment analyses showed that the DEGs were significantly enriched in the biological processes (BPs) of purine-related metabolic processes and signaling, especially the common DEGs, which were enriched in some immunological processes. Most of the DEGs were enriched in signaling pathways associated with the immune system, some immune diseases and infectious disease pathways. Through a protein–protein interaction (PPI) network analysis and a gene expression regulatory network constructed with MS-related miRNAs, we confirmed FOS, TP53, VEGFA, JUN, HIF1A, RB1, PTGS2, CXCL8, OAS2, NFKBIA and OAS1 as candidate genes of MS. Furthermore , we explored the potential SNPs associated with MS by database mining. In conclusion, this study provides the identified genes, SNPs, biological processes, and cellular pathways associated with MS. The uncovered candidate genes may be potential biomarkers involved in the diagnosis and therapy of MS

Alteration in voltage-dependent calcium channels in dog basilar artery after subarachnoid hemorrhage: Laboratory investigation

Object. The L-type Ca++ channel antagonists like nimodipine have limited efficacy against vasospasm after subarachnoid hemorrhage (SAH). The authors tested the hypothesis that this is because SAH alters these channels, rendering them less responsible for contraction. Methods. Basilar artery smooth muscle cells were isolated 4, 7, and 21 days after SAH in dogs, and Ca ++ channel currents were recorded in 10-mmol/L barium. Proteins for α1 subunits of L-type Ca++ channels were measured by immunoblotting and isometric tension recordings done on rings of the basilar artery. Results. High voltage - activated (HVA) Ca++ channel currents were significantly decreased and low voltage - activated (LVA) currents increased during vasospasm 4, 7, and 21 days after SAH (p \u3c 0.05). Vasospasm was associated with a significant decrease in the number of cells with negligible LVA current while the number of cells in which the LVA current formed greater than 50% of the maximal current increased (p \u3c 0.01). Window currents through LVA and HVA channels were significantly reduced. All changes correlated with the severity of vasospasm. There was an increase in protein for Cav3.1 and Cav3.3 α1 subunits that comprise T-type Ca++ channels, a decrease in L-type (Ca v1.2 and Cav1.3) and an increase in R-type (Ca v2.3) Ca++ channel α1 subunits. Functionally, however, isometric tension studies showed vasospastic arteries still relaxed with nimodipine. Conclusions. Voltage-dependent Ca++ channels are altered in cerebral arteries after SAH. While decreased L-type channels may account for the lack of efficacy of nimodipine clinically, there may be other reasons such as inadequate dose, effect of nimodipine on other cellular targets, and mechanisms of vasospasm other than smooth muscle contraction mediated by activation of L-type Ca++ channels

Alteration in voltage-dependent calcium channels in dog basilar artery after subarachnoid hemorrhage: Laboratory investigation

Object. The L-type Ca++ channel antagonists like nimodipine have limited efficacy against vasospasm after subarachnoid hemorrhage (SAH). The authors tested the hypothesis that this is because SAH alters these channels, rendering them less responsible for contraction. Methods. Basilar artery smooth muscle cells were isolated 4, 7, and 21 days after SAH in dogs, and Ca ++ channel currents were recorded in 10-mmol/L barium. Proteins for α1 subunits of L-type Ca++ channels were measured by immunoblotting and isometric tension recordings done on rings of the basilar artery. Results. High voltage - activated (HVA) Ca++ channel currents were significantly decreased and low voltage - activated (LVA) currents increased during vasospasm 4, 7, and 21 days after SAH (p \u3c 0.05). Vasospasm was associated with a significant decrease in the number of cells with negligible LVA current while the number of cells in which the LVA current formed greater than 50% of the maximal current increased (p \u3c 0.01). Window currents through LVA and HVA channels were significantly reduced. All changes correlated with the severity of vasospasm. There was an increase in protein for Cav3.1 and Cav3.3 α1 subunits that comprise T-type Ca++ channels, a decrease in L-type (Ca v1.2 and Cav1.3) and an increase in R-type (Ca v2.3) Ca++ channel α1 subunits. Functionally, however, isometric tension studies showed vasospastic arteries still relaxed with nimodipine. Conclusions. Voltage-dependent Ca++ channels are altered in cerebral arteries after SAH. While decreased L-type channels may account for the lack of efficacy of nimodipine clinically, there may be other reasons such as inadequate dose, effect of nimodipine on other cellular targets, and mechanisms of vasospasm other than smooth muscle contraction mediated by activation of L-type Ca++ channels

Anterior circulation mouse model of subarachnoid hemorrhage

A model of subarachnoid hemorrhage (SAH) first described in rats where blood is injected into the prechiasmatic cistern was adapted to mice. The hypothesis was that such an anterior circulation SAH model would produce vasospasm of greater severity and longer duration than other mouse models. The goal was to create a mouse model that could then be used in transgenic and knockout animals in order to further knowledge of SAH and vasospasm. A needle was inserted stereotactically into the prechiasmatic cistern and 100 μl autologous arterial blood injected over seconds (n = 10). Effects were compared to injection of saline (n = 10) or to sham operation (n = 7). Monitoring of cerebral blood flow by laser Doppler showed a statistically similar decrease during injection in both groups. 7 days after SAH there was vasospasm of the middle and anterior cerebral arteries (51% reduction in MCA radius in SAH compared to saline-injected group, P \u3c 0.009, Student\u27s t-test). In order to determine if SAH in this model was associated with neuronal injury, brains were examined for TUNEL and fluoro-jade-positive cells. 60% of SAH but not saline-injected mice exhibited TUNEL-positive cells in the cerebral cortex and 30% of the SAH but no saline-injected mice had fluoro-jade positive cells in the cortex, hippocampus and dentate gyrus. The model is simple to perform and may be useful for investigating the pathophysiology of SAH. © 2009 Elsevier B.V. All rights reserved