PMID- 30489210
OWN - NLM
STAT- MEDLINE
DCOM- 20191127
LR  - 20220129
IS  - 1747-4949 (Electronic)
IS  - 1747-4930 (Linking)
VI  - 14
IP  - 2
DP  - 2019 Feb
TI  - The effect of rapamycin treatment on cerebral ischemia: A systematic review and 
      meta-analysis of animal model studies.
PG  - 137-145
LID - 10.1177/1747493018816503 [doi]
AB  - BACKGROUND: Amplifying endogenous neuroprotective mechanisms is a promising 
      avenue for stroke therapy. One target is mammalian target of rapamycin (mTOR), a 
      serine/threonine kinase regulating cell proliferation, cell survival, protein 
      synthesis, and autophagy. Animal studies investigating the effect of rapamycin on 
      mTOR inhibition following cerebral ischemia have shown conflicting results. AIM: 
      To conduct a systematic review and meta-analysis evaluating the effectiveness of 
      rapamycin in reducing infarct volume in animal models of ischemic stroke. SUMMARY 
      OF REVIEW: Our search identified 328 publications. Seventeen publications met 
      inclusion criteria (52 comparisons: 30 reported infarct size and 22 reported 
      neurobehavioral score). Study quality was modest (median 4 of 9) with no evidence 
      of publication bias. The point estimate for the effect of rapamycin was a 21.6% 
      (95% CI, 7.6%-35.7% p < 0.01) improvement in infarct volume and 30.5% (95% CI 
      17.2%-43.8%, p < 0.0001) improvement in neuroscores. Effect sizes were greatest 
      in studies using lower doses of rapamycin. CONCLUSION: Low-dose rapamycin 
      treatment may be an effective therapeutic option for stroke. Modest study quality 
      means there is a potential risk of bias. We recommend further high-quality 
      preclinical studies on rapamycin in stroke before progressing to clinical trials.
FAU - Beard, Daniel J
AU  - Beard DJ
AUID- ORCID: 0000-0002-3720-7588
AD  - 1 Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, 
      Oxford, UK.
FAU - Hadley, Gina
AU  - Hadley G
AD  - 1 Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, 
      Oxford, UK.
AD  - 2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, 
      UK.
FAU - Thurley, Neal
AU  - Thurley N
AUID- ORCID: 0000-0003-0770-7298
AD  - 3 Bodleian Healthcare Libraries, University of Oxford, Oxford, UK.
FAU - Howells, David W
AU  - Howells DW
AD  - 4 School of Medicine, College of Health and Medicine, University of Tasmania, 
      Hobart, Australia.
FAU - Sutherland, Brad A
AU  - Sutherland BA
AD  - 4 School of Medicine, College of Health and Medicine, University of Tasmania, 
      Hobart, Australia.
FAU - Buchan, Alastair M
AU  - Buchan AM
AUID- ORCID: 0000-0002-2918-5200
AD  - 1 Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, 
      Oxford, UK.
AD  - 5 Medical Sciences Division, University of Oxford, Oxford, UK.
AD  - 6 Acute Vascular Imaging Centre, University of Oxford, Oxford University 
      Hospitals, Oxford, UK.
LA  - eng
GR  - MR/M022757/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20181129
PL  - United States
TA  - Int J Stroke
JT  - International journal of stroke : official journal of the International Stroke 
      Society
JID - 101274068
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Neuroprotective Agents)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/*drug therapy
MH  - Cerebellum/*pathology
MH  - Disease Models, Animal
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Neuroprotective Agents/*therapeutic use
MH  - Sirolimus/*therapeutic use
MH  - Stroke/*drug therapy
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Experimental stroke
OT  - infarct volume
OT  - mTOR
OT  - meta-analysis
OT  - rapamycin
OT  - systematic review
EDAT- 2018/11/30 06:00
MHDA- 2019/11/28 06:00
CRDT- 2018/11/30 06:00
PHST- 2018/11/30 06:00 [pubmed]
PHST- 2019/11/28 06:00 [medline]
PHST- 2018/11/30 06:00 [entrez]
AID - 10.1177/1747493018816503 [doi]
PST - ppublish
SO  - Int J Stroke. 2019 Feb;14(2):137-145. doi: 10.1177/1747493018816503. Epub 2018 
      Nov 29.