Evidence map›Paper›PMID 32357505›Full record

ArticleInternational journal of molecular sciences2020

Comparative Cerebroprotective Potential of d- and l-Carnosine Following Ischemic Stroke in Mice.

Saurabh Jain, Eun-Sun Kim, Donghyun Kim, David Burrows, Milena De Felice, Minyeong Kim, Seung-Hoon Baek, Ali Ali, Jessica Redgrave, Thorsten R Doeppner and 3 more

Open access · goldAbstract readComparative Study
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 25 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Saurabh JainDepartment of Neuroscience, SITraN, University of Sheffield, Sheffield S10 2HQ, UK.
Eun-Sun KimCollege of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Korea.
Donghyun KimCollege of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Korea.
David BurrowsDepartment of Neuroscience, SITraN, University of Sheffield, Sheffield S10 2HQ, UK.
Milena De FeliceDepartment of Neuroscience, SITraN, University of Sheffield, Sheffield S10 2HQ, UK.ORCID 0000-0001-5729-6525
Minyeong KimCollege of Pharmacy and Research, Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Korea.
Seung-Hoon BaekCollege of Pharmacy and Research, Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Korea.ORCID 0000-0002-4166-057X
Ali AliDepartment of Neuroscience, SITraN, University of Sheffield, Sheffield S10 2HQ, UK.
Jessica RedgraveDepartment of Neuroscience, SITraN, University of Sheffield, Sheffield S10 2HQ, UK.
Thorsten R DoeppnerDepartment of Neurology, University Medical Center Goettingen, 37075 Goettingen, Germany.
Iain GardnerTranslation DMPK Sciences, Simcyp Division, Certara, Sheffield S1 2BJ, UK.
Ok-Nam BaeCollege of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Korea.ORCID 0000-0003-0583-2116
Arshad MajidDepartment of Neuroscience, SITraN, University of Sheffield, Sheffield S10 2HQ, UK.
University of Sheffield · GBHanyang University · KRAjou University · KRSimcyp (United Kingdom) · GB

Funding

Medical Research Council MR/R005923/1National Research Foundation of Korea NRF-2017R1C1B3002626
6 · The paper itself

Abstract

l-carnosine is an attractive therapeutic agent for acute ischemic stroke based on its robust preclinical cerebroprotective properties and wide therapeutic time window. However, large doses are needed for efficacy because carnosine is rapidly degraded in serum by carnosinases. The need for large doses could be particularly problematic when translating to human studies, as humans have much higher levels of serum carnosinases. We hypothesized that d-carnosine, which is not a substrate for carnosinases, may have a better pharmacological profile and may be more efficacious at lower doses than l-carnosine. To test our hypothesis, we explored the comparative pharmacokinetics and neuroprotective properties of d- and L-carnosine in acute ischaemic stroke in mice. We initially investigated the pharmacokinetics of d- and L-carnosine in serum and brain after intravenous (IV) injection in mice. We then investigated the comparative efficacy of d- and l-carnosine in a mouse model of transient focal cerebral ischemia followed by in vitro testing against excitotoxicity and free radical generation using primary neuronal cultures. The pharmacokinetics of d- and l-carnosine were similar in serum and brain after IV injection in mice. Both d- and l-carnosine exhibited similar efficacy against mouse focal cerebral ischemia. In vitro studies in neurons showed protection against excitotoxicity and the accumulation of free radicals. d- and l-carnosine exhibit similar pharmacokinetics and have similar efficacy against experimental stroke in mice. Since humans have far higher levels of carnosinases, d-carnosine may have more favorable pharmacokinetics in future human studies.

Indexed as

AnimalsBrain ChemistryCarnosineCells, CulturedDisease Models, AnimalHumansInjections, IntravenousIschemic StrokeMaleMiceNeuronsNeuroprotective AgentsPrimary Cell CultureCarnosineNeuroprotective Agentsd- and l-carnosineefficacyMCAOneuroprotectionpharmacokineticsstroke

Identifiers

PMID32357505
PMCPMC7246848
OpenAlexW3018847363

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.