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Endothelin-1 induced focal ischaemia : a novel model of spinal cord injury

Endothelin-1 induced focal ischaemia : a novel model of spinal cord injury
Endothelin-1 induced focal ischaemia : a novel model of spinal cord injury

A novel model of SCI has been generated in which microinjection of the vasoconstricting peptide endothelin-1 (ET-1) into the ventral grey matter of the rat spinal cord is used to generate an atraumatic focal ischaemic lesion.  Within 15 minutes of microinjection of 15pmol ET-1, blood flow in the spinal cord is reduced by 90%, the remains below baseline values for at least one hour.  Neurons and astrocytes are destroyed by the ischaemia within 6 hours, and there is widespread astrocyte activation in adjacent areas.  There is a profound acute inflammatory response characterised by peak recruitment of neutrophils at 24 hours, and macrophages are present in the grey and white matter from 3 days to at least 21 days after microinjection.  Macrophage numbers are maintained in the white matter from 7 to 21 days, whereas in the grey matter the number of macrophages decreases at this time.

Histological evidence of axonal injury, in the form of amyloid precursor protein (APP) positive axon profiles and ‘end-bulb’-like structures, is present 24 hours and 3 days after microinjection of ET-1 but not vehicle.  Examination of the ventral white matter axons 3 days after microinjection of ET-1 using electron microscopy revealed substantial injury to the axoplasm but less injury to myelin sheaths.  Microinjection of the excitotoxin N-methyl-D-aspartate into the ventral grey matter of the spinal cord resulted in more extensive myelin injury and sparing of axoplasm, which suggests that the axonal injury seen after ET-1 is not solely due to release of glutamate from injured neurons and is likely to be the result of ischaemia.

This model presents a novel opportunity to study the mechanisms of secondary injury, particularly with respect to axonal injury, in an atraumatic setting.  All the characteristics of conventional SCI models are reproduced but without paralysis of the animals or the involvement of direct mechanical injury.

University of Southampton
Corkill, Dominic John
Corkill, Dominic John

Corkill, Dominic John (2003) Endothelin-1 induced focal ischaemia : a novel model of spinal cord injury. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

A novel model of SCI has been generated in which microinjection of the vasoconstricting peptide endothelin-1 (ET-1) into the ventral grey matter of the rat spinal cord is used to generate an atraumatic focal ischaemic lesion.  Within 15 minutes of microinjection of 15pmol ET-1, blood flow in the spinal cord is reduced by 90%, the remains below baseline values for at least one hour.  Neurons and astrocytes are destroyed by the ischaemia within 6 hours, and there is widespread astrocyte activation in adjacent areas.  There is a profound acute inflammatory response characterised by peak recruitment of neutrophils at 24 hours, and macrophages are present in the grey and white matter from 3 days to at least 21 days after microinjection.  Macrophage numbers are maintained in the white matter from 7 to 21 days, whereas in the grey matter the number of macrophages decreases at this time.

Histological evidence of axonal injury, in the form of amyloid precursor protein (APP) positive axon profiles and ‘end-bulb’-like structures, is present 24 hours and 3 days after microinjection of ET-1 but not vehicle.  Examination of the ventral white matter axons 3 days after microinjection of ET-1 using electron microscopy revealed substantial injury to the axoplasm but less injury to myelin sheaths.  Microinjection of the excitotoxin N-methyl-D-aspartate into the ventral grey matter of the spinal cord resulted in more extensive myelin injury and sparing of axoplasm, which suggests that the axonal injury seen after ET-1 is not solely due to release of glutamate from injured neurons and is likely to be the result of ischaemia.

This model presents a novel opportunity to study the mechanisms of secondary injury, particularly with respect to axonal injury, in an atraumatic setting.  All the characteristics of conventional SCI models are reproduced but without paralysis of the animals or the involvement of direct mechanical injury.

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Published date: 2003

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Local EPrints ID: 465174
URI: http://eprints.soton.ac.uk/id/eprint/465174
PURE UUID: 59672c4d-0bf2-41d9-8bc5-27e539534554

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Date deposited: 05 Jul 2022 00:27
Last modified: 05 Jul 2022 04:27

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Author: Dominic John Corkill

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