- Overview
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Species
RatStrain common name
-Full nomenclature
-Genetic background
Sprague DawleyOriginal publication of model
-Breeding scheme
-Type of model
Haemorrhagic stroke - Availability
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Principal investigator
Stuart AllanInstitution
University of ManchesterNamed contact
Josie ThomasContact email
josephine.thomas@manchester.ac.ukSource of model
SupplierSupplier code
Charles RiverMTA Holder and Issuing Organisation:
- - Intervention details
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Intervention
HaemorrhagicStandard Operating Procedures for Intervention
https://drive.google.com/open?id=1JR04N9Fcdl26K7-vp1pTxhdP-syx3X5JAge at Surgery
8-10 weeksAnaesthetic
Isoflurane. 5% to induce, maintained at 2-2.5% throughout surgeryAnalgesics
Topical EMLA. 0.06mg/kg buprenorphine administered s.c. Immediately following anaesthetic inductionAntibiotics
None - Study details
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Sex
MaleAge of model
8-10 weeksDuration of Study
Up to 14 daysDiet
Standard chow - for 72h post-surgery animals receive normal diet pellets softened with water to improve feedingCage enrichment and housing
Group housing, 2-5 animals/cage. Enrichment with sizzle nesting, chewing sticks, play tunnels, and seedsTypes of outcomes measured
Inflammatory responseNeurobehaviour (i.e. sensory, motor, cognition)NeuroscorePhysiology (i.e. body weight, BP)Structural measure (i.e. IHC, EM, structural MRI)Vascular function (i.e. BBB integrity, CBF)Details of Outcomes Measured
Weight, modified neurological severity score, Behaviour (cylinder test, corner turn test), tissue pathology using immunohistochemistry and MRI (T2, dynamic contrast enhanced to assess BBB integrity, neurite orientation dispersion and density imaging to assess diffusion metrics and tissue microarchitecture), brain and systemic inflammation (cytokine assays).
Standard Operating Procedures for Intervention
https://drive.google.com/open?id=1JR04N9Fcdl26K7-vp1pTxhdP-syx3X5JStrengths of Model
- Appropriate modelling of haematoma expansion (unlike autologous blood model)
- Straightforward protocol and relatively easy surgery to perform
- Could be easily modified to target other brain regions e.g. cortex, internal capsule, cerebellum
- Induces behavioural deficits lasting at least 14 days
- Largely consistent bleed sizesLimitations of Model
- Collagenase induces rupture of multiple small blood vessels at injection site rather than a single vessel (artery) as seen in human ICH
- Possible concerns of inflammatory actions of collagenase which may exacerbate endogenous inflammatory mechanisms
Image
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Intracerebral haemorrhage in the striatum model
Haemorrhagic stroke