Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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Improving Cognitive Outcome in Cerebral Malaria: Insights from Clinical and Experimental Research

Author(s): Aline Silva de Miranda, Fatima Brant, Fabiana Simao Machado, Milene Alvarenga Rachid, Antonio Lucio Teixeira.

Abstract:

Cerebral Malaria (CM) is a clinical syndrome defined by the World Health Organization (WHO) as a potentially reversible diffuse encephalopathy characterized mainly by coma and the presence of asexual forms of Plasmodium falciparum parasites in peripheral blood smears in the absence of other causes of encephalopathy. A wide range of clinical manifestations follows the disease including cognitive, behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms of CM pathogenesis remain incompletely understood although vascular, immunological and metabolic changes have been described. The classical treatment of CM is based on the administration of antimalarial drugs, especially chloroquine and artemisinin derivates as artesunate. Even with treatment, 15 to 20% of children with CM die and approximately 10 to 17% of those who survive remain with significant long-term cognitive impairment. In this context, neuroprotective and adjuvant therapies have been recently investigated in clinical and experimental studies of CM in an attempt to improve cognitive outcome. A poor understanding of pathophysiological mechanisms, properties of compounds used and patient selection have contributed to the lack of success of these interventions. This review discusses clinical aspects of cognitive sequelae, possible mechanisms involved in the brain injury, perspectives and limitations regarding the pharmacological strategies to improve cognitive outcome in CM.

Keywords: cognitive impairment, malaria, Adjuvant therapies, cerebral malaria, pharmacological strategies, neuroprotective interventions, mitochondrial dysfunction, synaptic plasticity

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Article Details

VOLUME: 11
ISSUE: 4
Year: 2011
Page: [285 - 295]
Pages: 11
DOI: 10.2174/1871524911106040285
Price: $58