Assessment of R18, COG1410, and APP96-110 in excitotoxicity and traumatic brain injury

Li Shan Chiu, Ryan Scott Anderton, Jane Louise Cross, Vincent William Clark, Adam B. Edwards, Neville W Knuckey, Bruno Meloni

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Cationic arginine-rich and poly-arginine peptides (referred to as CARPs) have potent neuroprotective properties in in vitro excitotoxicity and in vivo models of stroke. Traumatic brain injury (TBI) shares many pathophysiological processes as stroke, including excitotoxicity. Therefore, we evaluated our lead peptide, poly-arginine R18, with the COG1410 and APP96-110 peptides, which have neuroprotective actions following TBI. In an in vitro cortical neuronal glutamic acid excitotoxicity injury model, R18 was highly neuroprotective and reduced neuronal calcium influx, while COG1410 and APP96-110 displayed modest neuroprotection and were less effective at reducing calcium influx. In an impact-acceleration closed-head injury model (Marmarou model), R18, COG1410, and APP96-110 were administered intravenously (300 nmol/kg) at 30 minutes after injury in male Sprague-Dawley rats. When compared to vehicle, no peptide significantly improved functional outcomes, however the R18 and COG1410 treatment groups displayed positive trends in the adhesive tape test and rotarod assessments. Similarly, no peptide had a significant effect on hippocampal neuronal loss, however a significant reduction in axonal injury was observed for R18 and COG1410. In conclusion, this study has demonstrated that R18 is significantly more effective than COG1410 and APP96-110 at reducing neuronal injury and calcium influx following excitotoxicity, and that both R18 and COG1410 reduce axonal injury following TBI. Additional dose response and treatment time course studies are required to further assess the efficacy of R18 in TBI.

Original languageEnglish
Pages (from-to)147-157
JournalTranslational Neuroscience
Volume8
Issue number1
DOIs
Publication statusPublished - 15 Nov 2017

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Peptides
Wounds and Injuries
Arginine
Calcium
Stroke
Rotarod Performance Test
Closed Head Injuries
COG1410
Traumatic Brain Injury
Adhesives
Sprague Dawley Rats
Glutamic Acid
In Vitro Techniques

Cite this

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title = "Assessment of R18, COG1410, and APP96-110 in excitotoxicity and traumatic brain injury",
abstract = "Cationic arginine-rich and poly-arginine peptides (referred to as CARPs) have potent neuroprotective properties in in vitro excitotoxicity and in vivo models of stroke. Traumatic brain injury (TBI) shares many pathophysiological processes as stroke, including excitotoxicity. Therefore, we evaluated our lead peptide, poly-arginine R18, with the COG1410 and APP96-110 peptides, which have neuroprotective actions following TBI. In an in vitro cortical neuronal glutamic acid excitotoxicity injury model, R18 was highly neuroprotective and reduced neuronal calcium influx, while COG1410 and APP96-110 displayed modest neuroprotection and were less effective at reducing calcium influx. In an impact-acceleration closed-head injury model (Marmarou model), R18, COG1410, and APP96-110 were administered intravenously (300 nmol/kg) at 30 minutes after injury in male Sprague-Dawley rats. When compared to vehicle, no peptide significantly improved functional outcomes, however the R18 and COG1410 treatment groups displayed positive trends in the adhesive tape test and rotarod assessments. Similarly, no peptide had a significant effect on hippocampal neuronal loss, however a significant reduction in axonal injury was observed for R18 and COG1410. In conclusion, this study has demonstrated that R18 is significantly more effective than COG1410 and APP96-110 at reducing neuronal injury and calcium influx following excitotoxicity, and that both R18 and COG1410 reduce axonal injury following TBI. Additional dose response and treatment time course studies are required to further assess the efficacy of R18 in TBI.",
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Assessment of R18, COG1410, and APP96-110 in excitotoxicity and traumatic brain injury. / Chiu, Li Shan; Anderton, Ryan Scott; Cross, Jane Louise; Clark, Vincent William; Edwards, Adam B.; Knuckey, Neville W; Meloni, Bruno.

In: Translational Neuroscience, Vol. 8, No. 1, 15.11.2017, p. 147-157.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Assessment of R18, COG1410, and APP96-110 in excitotoxicity and traumatic brain injury

AU - Chiu, Li Shan

AU - Anderton, Ryan Scott

AU - Cross, Jane Louise

AU - Clark, Vincent William

AU - Edwards, Adam B.

AU - Knuckey, Neville W

AU - Meloni, Bruno

PY - 2017/11/15

Y1 - 2017/11/15

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AB - Cationic arginine-rich and poly-arginine peptides (referred to as CARPs) have potent neuroprotective properties in in vitro excitotoxicity and in vivo models of stroke. Traumatic brain injury (TBI) shares many pathophysiological processes as stroke, including excitotoxicity. Therefore, we evaluated our lead peptide, poly-arginine R18, with the COG1410 and APP96-110 peptides, which have neuroprotective actions following TBI. In an in vitro cortical neuronal glutamic acid excitotoxicity injury model, R18 was highly neuroprotective and reduced neuronal calcium influx, while COG1410 and APP96-110 displayed modest neuroprotection and were less effective at reducing calcium influx. In an impact-acceleration closed-head injury model (Marmarou model), R18, COG1410, and APP96-110 were administered intravenously (300 nmol/kg) at 30 minutes after injury in male Sprague-Dawley rats. When compared to vehicle, no peptide significantly improved functional outcomes, however the R18 and COG1410 treatment groups displayed positive trends in the adhesive tape test and rotarod assessments. Similarly, no peptide had a significant effect on hippocampal neuronal loss, however a significant reduction in axonal injury was observed for R18 and COG1410. In conclusion, this study has demonstrated that R18 is significantly more effective than COG1410 and APP96-110 at reducing neuronal injury and calcium influx following excitotoxicity, and that both R18 and COG1410 reduce axonal injury following TBI. Additional dose response and treatment time course studies are required to further assess the efficacy of R18 in TBI.

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DO - 10.1515/tnsci-2017-0021

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JO - Translational Neuroscience

JF - Translational Neuroscience

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IS - 1

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