PMID- 28676008
OWN - NLM
STAT- MEDLINE
DCOM- 20190410
LR  - 20190410
IS  - 2212-3938 (Electronic)
IS  - 1574-8847 (Linking)
VI  - 12
IP  - 2
DP  - 2017
TI  - Repurposing Pharmaceuticals as Neuroprotective Agents for Cerebral Malaria.
PG  - 62-72
LID - 10.2174/1574884712666170704144042 [doi]
AB  - BACKGROUND: Cerebral malaria (CM) is a severe complication of Plasmodium 
      falciparum infection which may result in death or developmental disability. The 
      pathologic processes leading to CM are not fully elucidated; however, widely 
      accepted mechanisms include parasite sequestration, release of infected red blood 
      cell contents, activation of endothelial cells, increased inflammatory responses, 
      and ultimately dysfunction of the neurovascular unit (NVU). The endothelium plays 
      a central role in these processes as the site of parasitized erythrocyte 
      sequestration and as the regulator of fluid extravasation into the central 
      nervous system. Modulating endothelial barrier function at the NVU may provide 
      new therapeutic approaches to improve outcomes in CM. METHODS: Here we provide a 
      narrative review of the literature of peer-reviewed research relating to 
      adjunctive therapies for CM. We discuss regulatory pathways of the NVU, with a 
      focus on the potential for pharmacologic modulation of the NVU to improve CM 
      outcomes. RESULTS: Recently licensed pharmaceuticals, developed as therapies for 
      cancer or neurologic disease, could be re-purposed for use as host-directed 
      therapies in CM to target pathways involved in endothelial stability and 
      activation. CONCLUSION: The findings of this review highlight recently licensed 
      pharmaceuticals that may be developed as future adjunctive therapies for CM.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.org.
FAU - Brooks, Hannah M
AU  - Brooks HM
AD  - Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
FAU - Hawkes, Michael T
AU  - Hawkes MT
AD  - Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Clin Pharmacol
JT  - Current clinical pharmacology
JID - 101273158
RN  - 0 (Neuroprotective Agents)
SB  - IM
MH  - Animals
MH  - *Drug Repositioning
MH  - Humans
MH  - Malaria, Cerebral/*prevention & control
MH  - Malaria, Falciparum/complications/parasitology
MH  - Neuroprotective Agents/*therapeutic use
MH  - Plasmodium falciparum/isolation & purification
OTO - NOTNLM
OT  - Cerebral malaria
OT  - adjunctive therapies
OT  - cerebral edema
OT  - childhood morbidity
OT  - endothelial cells.
OT  - infectious disease
OT  - neuroprotective
EDAT- 2017/07/06 06:00
MHDA- 2019/04/11 06:00
CRDT- 2017/07/06 06:00
PHST- 2017/03/31 00:00 [received]
PHST- 2017/06/09 00:00 [revised]
PHST- 2017/06/21 00:00 [accepted]
PHST- 2017/07/06 06:00 [pubmed]
PHST- 2019/04/11 06:00 [medline]
PHST- 2017/07/06 06:00 [entrez]
AID - CCP-EPUB-84491 [pii]
AID - 10.2174/1574884712666170704144042 [doi]
PST - ppublish
SO  - Curr Clin Pharmacol. 2017;12(2):62-72. doi: 10.2174/1574884712666170704144042.