LPS Nigral Infusion Model — Melissa K. McCoy | ReplicateScience

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LPS Nigral Infusion Model — Melissa K. McCoy | ReplicateScience

1

Prepare XENP345 and LPS for coinfusion

Prepare the engineered dominant-negative TNF compound XENP345 and bacterial lipopolysaccharide (LPS) for chronic in vivo coinfusion into the substantia nigra

Not specified in provided textNot specified in provided text

Note: XENP345 is a PEGylated version of TNF variant A145R/I97T

View evidence from paper

“chronic in vivo coinfusion of XENP345 with bacterial lipopolysaccharide (LPS) into the substantia nigra”

2

Perform nigral infusion surgery

Conduct stereotaxic surgery to implant infusion cannula into the substantia nigra for chronic coinfusion of XENP345 and LPS

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Note: XENP345 was neuroprotective only when infused into the nigra, not the striatum

View evidence from paper

“XENP345 was neuroprotective only when infused into the nigra, not the striatum”

3

Initiate chronic coinfusion

Begin chronic in vivo coinfusion of XENP345 with bacterial lipopolysaccharide (LPS) into the substantia nigra

Chronic (duration not specified in provided text)Not specified in provided text

Note: This procedure induces neuroinflammation and nigral degeneration

View evidence from paper

“chronic in vivo coinfusion of XENP345 with bacterial lipopolysaccharide (LPS) into the substantia nigra”

4

Assess amphetamine-induced rotational behavior

Measure amphetamine-induced rotational behavior in rats to assess preservation of striatal dopamine levels

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Note: Attenuated rotational behavior indicates preservation of dopaminergic function

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“XENP345/6-OHDA rats displayed attenuated amphetamine-induced rotational behavior, indicating preservation of striatal dopamine levels”

5

Analyze nigral degeneration

Evaluate the extent of nigral degeneration and compare between treatment groups receiving XENP345 coinfusion versus LPS alone

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Note: Similar protective effects were observed with chronic coinfusion of XENP345 with LPS into substantia nigra

View evidence from paper

“Similar protective effects were observed with chronic in vivo coinfusion of XENP345 with bacterial lipopolysaccharide (LPS) into the substantia nigra”