NNZ-2566 treatment inhibits neuroinflammation and pro-inflammatory cytokine expression induced by experimental penetrating ballistic-like brain injury in rats.

Wei HH, Lu XC, Shear DA, Waghray A, Yao C, Tortella FC, Dave JR

Journal of neuroinflammation5 Aug 2009Cited by 61 (Europe PMC)

PMID19656406PMCIDPMC2731085DOI10.1186/1742-2094-6-19PepBankPUB-19656406

Summary

BackgroundInflammatory cytokines play a crucial role in the pathophysiology of traumatic brain injury (TBI), exerting either deleterious effects on the progression of tissue damage or beneficial roles during recovery and repair. NNZ-2566, a synthetic analogue of the neuroprotective tripeptide Glypromate, has been shown to be neuroprotective in animal models of brain injury. The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI) in rats.MethodsNNZ-2566 or vehicle (saline) was administered intravenously as a bolus injection (10 mg/kg) at 30 min post-injury, immediately followed by a continuous infusion of NNZ-2566 (3 mg/kg/h), or equal volume of vehicle, for various durations. Inflammatory cytokine gene expression from the brain tissue of rats exposed to PBBI was evaluated using microarray, quantitative real time PCR (QRT-PCR), and enzyme-linked immunosorbent assay (ELISA) array. Histopathology of the injured brains was examined using hematoxylin and eosin (H&E) and immunocytochemistry of inflammatory cytokine IL-1beta.ResultsNNZ-2566 treatment significantly reduced injury-mediated up-regulation of IL-1beta, TNF-alpha, E-selectin and IL-6 mRNA during the acute injury phase. ELISA cytokine array showed that NZ-2566 treatment significantly reduced levels of the pro-inflammatory cytokines IL-1beta, TNF-alpha and IFN-gamma in the injured brain, but did not affect anti-inflammatory cytokine IL-6 levels.ConclusionCollectively, these results suggest that the neuroprotective effects of NNZ-2566 may, in part, be functionally attributed to the compound's ability to modulate expression of multiple neuroinflammatory mediators in the injured brain.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Mechanism
In rats with PBBI, NNZ-2566 significantly reduced injury-mediated IL-1beta mRNA upregulation versus saline.
In plain wordsIn rats with brain injury, NNZ-2566 reduced IL-1beta mRNA upregulation versus saline.
Peptide
Trofinetide
Outcome
DecreaseIL-1beta mRNA
Study
ratn: not reported in source
Penetrating ballistic-like brain injury
Comparator
Saline vehicle
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
10 mg/kg bolus followed by 3 mg/kg/h infusion · intravenousAs given in this study (rat).
Source sentences
Summary
NNZ-2566 treatment significantly reduced injury-mediated up-regulation of IL-1beta, TNF-alpha, E-selectin and IL-6 mRNA during the acute injury phase.
2 context sentences(design, population, supporting numbers)
Summary · context
The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI) in rats.
Summary · context
NNZ-2566 or vehicle (saline) was administered intravenously as a bolus injection (10 mg/kg) at 30 min post-injury, immediately followed by a continuous infusion of NNZ-2566 (3 mg/kg/h), or equal volume of vehicle, for various durations.
Show in the study text Report a problemFND-1965640601
02AnimalAnimal study (in vivo)Mechanism
In rats with PBBI, NNZ-2566 significantly reduced injury-mediated TNF-alpha mRNA upregulation versus saline.
In plain wordsIn rats with brain injury, NNZ-2566 reduced TNF-alpha mRNA upregulation versus saline.
Peptide
Trofinetide
Outcome
DecreaseTNF-alpha mRNA
Study
ratn: not reported in source
Penetrating ballistic-like brain injury
Comparator
Saline vehicle
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
10 mg/kg bolus followed by 3 mg/kg/h infusion · intravenousAs given in this study (rat).
Source sentences
Summary
NNZ-2566 treatment significantly reduced injury-mediated up-regulation of IL-1beta, TNF-alpha, E-selectin and IL-6 mRNA during the acute injury phase.
2 context sentences(design, population, supporting numbers)
Summary · context
The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI) in rats.
Summary · context
NNZ-2566 or vehicle (saline) was administered intravenously as a bolus injection (10 mg/kg) at 30 min post-injury, immediately followed by a continuous infusion of NNZ-2566 (3 mg/kg/h), or equal volume of vehicle, for various durations.
Show in the study text Report a problemFND-1965640602
03AnimalAnimal study (in vivo)Mechanism
In rats with PBBI, NNZ-2566 significantly reduced injury-mediated E-selectin mRNA upregulation versus saline.
In plain wordsIn rats with brain injury, NNZ-2566 reduced E-selectin mRNA upregulation versus saline.
Peptide
Trofinetide
Outcome
DecreaseE-selectin mRNA
Study
ratn: not reported in source
Penetrating ballistic-like brain injury
Comparator
Saline vehicle
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
10 mg/kg bolus followed by 3 mg/kg/h infusion · intravenousAs given in this study (rat).
Source sentences
Summary
NNZ-2566 treatment significantly reduced injury-mediated up-regulation of IL-1beta, TNF-alpha, E-selectin and IL-6 mRNA during the acute injury phase.
2 context sentences(design, population, supporting numbers)
Summary · context
The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI) in rats.
Summary · context
NNZ-2566 or vehicle (saline) was administered intravenously as a bolus injection (10 mg/kg) at 30 min post-injury, immediately followed by a continuous infusion of NNZ-2566 (3 mg/kg/h), or equal volume of vehicle, for various durations.
Show in the study text Report a problemFND-1965640603
04AnimalAnimal study (in vivo)Mechanism
In rats with PBBI, NNZ-2566 significantly reduced injury-mediated IL-6 mRNA upregulation versus saline.
In plain wordsIn rats with brain injury, NNZ-2566 reduced IL-6 mRNA upregulation versus saline.
Peptide
Trofinetide
Outcome
DecreaseIL-6 mRNA
Study
ratn: not reported in source
Penetrating ballistic-like brain injury
Comparator
Saline vehicle
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
10 mg/kg bolus followed by 3 mg/kg/h infusion · intravenousAs given in this study (rat).
Source sentences
Summary
NNZ-2566 treatment significantly reduced injury-mediated up-regulation of IL-1beta, TNF-alpha, E-selectin and IL-6 mRNA during the acute injury phase.
2 context sentences(design, population, supporting numbers)
Summary · context
The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI) in rats.
Summary · context
NNZ-2566 or vehicle (saline) was administered intravenously as a bolus injection (10 mg/kg) at 30 min post-injury, immediately followed by a continuous infusion of NNZ-2566 (3 mg/kg/h), or equal volume of vehicle, for various durations.
Show in the study text Report a problemFND-1965640604
05AnimalAnimal study (in vivo)Mechanism
In rats with PBBI, NNZ-2566 significantly reduced brain IL-1beta levels versus saline.
In plain wordsIn rats with brain injury, NNZ-2566 reduced brain IL-1beta levels versus saline.
Peptide
Trofinetide
Outcome
DecreaseBrain IL-1beta protein
Study
ratn: not reported in source
Penetrating ballistic-like brain injury
Comparator
Saline vehicle
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
10 mg/kg bolus followed by 3 mg/kg/h infusion · intravenousAs given in this study (rat).
Source sentences
Summary
ELISA cytokine array showed that NZ-2566 treatment significantly reduced levels of the pro-inflammatory cytokines IL-1beta, TNF-alpha and IFN-gamma in the injured brain, but did not affect anti-inflammatory cytokine IL-6 levels.
2 context sentences(design, population, supporting numbers)
Summary · context
The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI) in rats.
Summary · context
NNZ-2566 or vehicle (saline) was administered intravenously as a bolus injection (10 mg/kg) at 30 min post-injury, immediately followed by a continuous infusion of NNZ-2566 (3 mg/kg/h), or equal volume of vehicle, for various durations.
Show in the study text Report a problemFND-1965640605
06AnimalAnimal study (in vivo)Mechanism
In rats with PBBI, NNZ-2566 significantly reduced brain TNF-alpha levels versus saline.
In plain wordsIn rats with brain injury, NNZ-2566 reduced brain TNF-alpha levels versus saline.
Peptide
Trofinetide
Outcome
DecreaseBrain TNF-alpha protein
Study
ratn: not reported in source
Penetrating ballistic-like brain injury
Comparator
Saline vehicle
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
10 mg/kg bolus followed by 3 mg/kg/h infusion · intravenousAs given in this study (rat).
Source sentences
Summary
ELISA cytokine array showed that NZ-2566 treatment significantly reduced levels of the pro-inflammatory cytokines IL-1beta, TNF-alpha and IFN-gamma in the injured brain, but did not affect anti-inflammatory cytokine IL-6 levels.
2 context sentences(design, population, supporting numbers)
Summary · context
The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI) in rats.
Summary · context
NNZ-2566 or vehicle (saline) was administered intravenously as a bolus injection (10 mg/kg) at 30 min post-injury, immediately followed by a continuous infusion of NNZ-2566 (3 mg/kg/h), or equal volume of vehicle, for various durations.
Show in the study text Report a problemFND-1965640606
07AnimalAnimal study (in vivo)Mechanism
In rats with PBBI, NNZ-2566 significantly reduced brain IFN-gamma levels versus saline.
In plain wordsIn rats with brain injury, NNZ-2566 reduced brain IFN-gamma levels versus saline.
Peptide
Trofinetide
Outcome
DecreaseBrain IFN-gamma protein
Study
ratn: not reported in source
Penetrating ballistic-like brain injury
Comparator
Saline vehicle
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
10 mg/kg bolus followed by 3 mg/kg/h infusion · intravenousAs given in this study (rat).
Source sentences
Summary
ELISA cytokine array showed that NZ-2566 treatment significantly reduced levels of the pro-inflammatory cytokines IL-1beta, TNF-alpha and IFN-gamma in the injured brain, but did not affect anti-inflammatory cytokine IL-6 levels.
2 context sentences(design, population, supporting numbers)
Summary · context
The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI) in rats.
Summary · context
NNZ-2566 or vehicle (saline) was administered intravenously as a bolus injection (10 mg/kg) at 30 min post-injury, immediately followed by a continuous infusion of NNZ-2566 (3 mg/kg/h), or equal volume of vehicle, for various durations.
Show in the study text Report a problemFND-1965640607
08AnimalAnimal study (in vivo)Mechanism
In rats with PBBI, NNZ-2566 did not affect brain IL-6 levels versus saline.
In plain wordsIn rats with brain injury, NNZ-2566 did not affect brain IL-6 levels versus saline.
Peptide
Trofinetide
Outcome
No significant changeBrain IL-6 protein
Study
ratn: not reported in source
Penetrating ballistic-like brain injury
Comparator
Saline vehicle
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
10 mg/kg bolus followed by 3 mg/kg/h infusion · intravenousAs given in this study (rat).
Source sentences
Summary
ELISA cytokine array showed that NZ-2566 treatment significantly reduced levels of the pro-inflammatory cytokines IL-1beta, TNF-alpha and IFN-gamma in the injured brain, but did not affect anti-inflammatory cytokine IL-6 levels.
2 context sentences(design, population, supporting numbers)
Summary · context
The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI) in rats.
Summary · context
NNZ-2566 or vehicle (saline) was administered intravenously as a bolus injection (10 mg/kg) at 30 min post-injury, immediately followed by a continuous infusion of NNZ-2566 (3 mg/kg/h), or equal volume of vehicle, for various durations.
Show in the study text Report a problemFND-1965640608

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:37 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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