ABSTRACT
Histology is the gold standard to unveil microscopic brain structures and pathological alterations in humans and animal models of disease. However, due to tedious manual interventions, quantification of histopathological markers is classically performed on a few tissue sections, thus restricting measurements to limited portions of the brain. Recently developed 3D microscopic imaging techniques have allowed in-depth study of neuroanatomy. However, quantitative methods are still lacking for whole-brain analysis of cellular and pathological markers. Here, we propose a ready-to-use, automated, and scalable method to thoroughly quantify histopathological markers in 3D in rodent whole brains. It relies on block-face photography, serial histology and 3D-HAPi (Three Dimensional Histology Analysis Pipeline), an open source image analysis software. We illustrate our method in studies involving mouse models of Alzheimer's disease and show that it can be broadly applied to characterize animal models of brain diseases, to evaluate therapeutic interventions, to anatomically correlate cellular and pathological markers throughout the entire brain and to validate in vivo imaging techniques.
Subject(s)
Alzheimer Disease/diagnostic imaging , Brain Mapping , Brain/diagnostic imaging , Imaging, Three-Dimensional , Alzheimer Disease/pathology , Animals , Brain/pathology , Brain/ultrastructure , Disease Models, Animal , Humans , Image Processing, Computer-Assisted , Mice , SoftwareABSTRACT
The standardized extract of Ginkgo biloba EGb 761 has been used to reduce cognitive dysfunction. The present study was designed to evaluate the effect of postischemic oral treatment with EGb 761 in a model of vascular dementia in gerbils. Daily oral posttreatment with EGb 761 led to a significant recovery of spatial memory assessed by the object location test, inhibited the decrease in plasma SOD activity and protected the hippocampal CA1 neurons, even when administered after the insult. These data provide further evidence for the therapeutic potential of EGb 761 in the treatment of vascular dementia.
Subject(s)
Dementia, Vascular/drug therapy , Ginkgo biloba , Hippocampus/drug effects , Memory Disorders/drug therapy , Neuroprotective Agents/therapeutic use , Phytotherapy , Plant Extracts/therapeutic use , Animals , Brain Ischemia/blood , Brain Ischemia/complications , Brain Ischemia/drug therapy , Dementia, Vascular/blood , Dementia, Vascular/pathology , Disease Models, Animal , Gerbillinae , Hippocampus/pathology , Memory/drug effects , Memory Disorders/blood , Nerve Degeneration/blood , Nerve Degeneration/drug therapy , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Superoxide Dismutase/bloodABSTRACT
A series of 4-arylimidazole carbamates was synthesized and their binding affinities to the site-2 sodium (Na+) channel were determined. SAR studies led to the identification of compound 10, a potent Na+ channel blocker which was efficacious in pain models in vivo.
Subject(s)
Carbamates/chemical synthesis , Carbamates/pharmacology , Imidazoles/chemical synthesis , Imidazoles/pharmacology , Pain/drug therapy , Pain/etiology , Peripheral Nervous System Diseases/complications , Sodium Channel Blockers/chemical synthesis , Sodium Channel Blockers/pharmacology , Animals , Batrachotoxins , Binding, Competitive/drug effects , Carrageenan , Humans , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Indicators and Reagents , Microsomes/drug effects , Microsomes/metabolism , Rats , Sodium/metabolism , Structure-Activity Relationship , Synaptosomes/drug effects , Synaptosomes/metabolism , Veratridine/pharmacologyABSTRACT
A series of 2-alkyl-4-arylimidazoles were prepared and their binding affinities to the site-2 sodium (Na+) channel were determined. SAR studies led to highly potent Na+ channel blockers.
Subject(s)
Sodium Channel Blockers/chemical synthesis , Sodium Channels/metabolism , Animals , Benzimidazoles/chemical synthesis , Benzimidazoles/pharmacology , Binding Sites , Brain/metabolism , Carbolines/chemistry , Cells, Cultured , Electrophysiology , Inhibitory Concentration 50 , Rats , Sodium Channel Blockers/pharmacology , Structure-Activity Relationship , Veratridine/pharmacologyABSTRACT
A series of hybrid compounds possessing an nNOS pharmacophore linked to an antioxidant fragment has been synthesized. Among them, compound 8d, a propofol derivative, displayed the greatest dual potencies against nNOS (IC(50)=0.12 microM) and lipid peroxidation (IC(50)=0.4 microM) accompanied with e/nNOS selectivity (67.5). This shows that nNOS was able to accommodate very bulky groups such as di-tert-butyl or di-iso-propyl phenol in its active site.
