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US 10,207,011 B2Granted
Methods, systems, and devices for an invertebrate model of traumatic brain injury
AssigneeWisconsin Alumni Research Foundation
InventorsBarry S. Ganetzky, David A. Wassarman
Life of this patent
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Abstract
Described herein are methods, systems, and devices for identifying agents and genetic pathways that modulate the effects of traumatic brain injury (TBI) in invertebrate model systems having a brain, e.g., Drosophila or C. elegans.
Claims17
A method for assaying a test agent in Drosophila, the method comprising the steps of:
- (i) delivering to one or more Drosophila individuals an impact to induce closed-head traumatic brain injury (TBI) wherein the step of delivering the impact comprises the steps of:
- (a) providing the one or more unrestrained Drosophila individuals inside one or more walled containers secured to a spring-loaded acceleration assembly having first and second ends and defining a deflectable long axis therebetween, the assembly fixedly secured at the first end to a base, the one or more containers secured to the assembly at the second end, the assembly configured to accelerate the one or more secured walled containers toward a strike surface upon deflection of the assembly on the long axis followed by release;
- and
- (b) deflecting the assembly on the long axis and releasing the deflected assembly, thereby accelerating the one or more secured walled containers toward and into contact with the strike surface, whereby the unrestrained Drosophila individuals in the one or more walled containers impact the one or more walled containers;
- (ii) dosing the one or more Drosophila individuals with a test agent before or after the impact;
- and
- (iii) after the impact, assessing in the dosed one or more Drosophila individuals the severity of a phenotype associated with closed-head TBI selected from the group consisting of lethality, an immune response, neurodegeneration, a sleep abnormality, a circadian abnormality, a learning deficit, a memory deficit, a social behavior deficit, a motor behavior deficit, changes in longevity, changes in intestinal barrier permeability, changes in mitochondrial structure and function, changes in gene expression, changes in enzymatic activity, changes in phosphorylation, changes in post-translational modification, changes in metabolite concentration, changes in cell death, changes in neurotransmitter signaling, and changes in microtubule structure.
4 more elements
A method for assaying a test agent in Drosophila, the method comprising the steps of:
- (i) delivering to one or more Drosophila individuals an impact to induce closed-head traumatic brain injury (TBI), wherein the step of delivering the impact comprises the steps of:
- (a) providing the one or more unrestrained Drosophila individuals inside one or more walled containers secured to a spring-loaded acceleration assembly having first and second ends and defining a deflectable long axis therebetween, the assembly fixedly secured at the first end to a base, the one or more containers secured to the assembly at the second end, the assembly configured to accelerate the one or more secured walled containers toward a strike surface upon deflection of the assembly on the long axis followed by release;
- and
- (b) deflecting the assembly on the long axis and releasing the assembly, thereby accelerating the one or more secured walled containers toward and into contact with the strike surface, whereby the unrestrained Drosophila individuals in the one or more walled containers impact the one or more walled containers;
- (ii) dosing the one or more individuals with a test agent before or after the impact;
- and
- (iii) after the impact, assessing closed-head TBI-associated lethality in the dosed one or more Drosophila.
4 more elements
Dependencies are inferred from the claim text.