Molecular targets in cerebral malaria for developing novel therapeutic strategies

•Elevated levels of pro-inflammatory cytokines and oxidative free radicals contribute to neuropathology in cerebral malaria.•Adjunctive anti-malarial therapy is essential for reducing the cognitive deficits for cerebral malaria.•Adjunctives targeting early pathological events must be studied in the...

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Bibliographic Details
Published in:Brain research bulletin 2020-04, Vol.157, p.100-107
Main Authors: Vanka, Ravisankar, Nakka, Venkata Prasuja, Kumar, Simhadri Praveen, Baruah, Uday Krishna, Babu, Phanithi Prakash
Format: Article
Language:English
Subjects:
Adjunctive therapy
Apoptosis
BBB integrity
Cerebral malaria
Inflammation
Oxidative stress
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Summary:•Elevated levels of pro-inflammatory cytokines and oxidative free radicals contribute to neuropathology in cerebral malaria.•Adjunctive anti-malarial therapy is essential for reducing the cognitive deficits for cerebral malaria.•Adjunctives targeting early pathological events must be studied in the animal models of cerebral malaria. Cerebral malaria (CM) is the severe neurological complication associated with Plasmodium falciparum infection. In clinical settings CM is predominantly characterized by fever, epileptic seizures, and asexual forms of parasite on blood smears, coma and even death. Cognitive impairment in the children and adults even after survival is one of the striking consequences of CM. Poor diagnosis often leads to inappropriate malaria therapy which in turn progress into a severe form of disease. Activation of multiple cell death pathways such as Inflammation, oxidative stress, apoptosis and disruption of blood brain barrier (BBB) plays critical role in the pathogenesis of CM and secondary brain damage. Thus, understanding such mechanisms of neuronal cell death might help to identify potential molecular targets for CM. Mitigation strategies for mortality rate and long-term cognitive deficits caused by existing anti-malarial drugs still remains a valid research question to ask. In this review, we discuss in detail about critical neuronal cell death mechanisms and the overall significance of adjunctive therapy with recent trends, which provides better insight towards establishing newer therapeutic strategies for CM.
ISSN:0361-9230
1873-2747
DOI:10.1016/j.brainresbull.2020.01.020