A Rapid Murine Coma and Behavior Scale for Quantitative Assessment of Murine Cerebral Malaria

• Published in: PloS one Vol. 5; no. 10; p. e13124
• Main Authors: Carroll, Ryan W., Wainwright, Mark S., Kim, Kwang-Youn, Kidambi, Trilokesh, Gómez, Noé D., Taylor, Terrie, Haldar, Kasturi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2010; Public Library of Science (PLoS)
• Subjects: Analysis; Animal models; Animals; Apolipoproteins; Apoptosis; Behavior; Behavior rating scales; Behavior, Animal; Cell Biology; Coma; Disease Models, Animal; Genotype & phenotype; Health aspects; Health care; Hemorrhage; House mouse; Infection; Infections; Infectious Diseases; Infectious Diseases/Neglected Tropical Diseases; Infectious Diseases/Tropical and Travel-Associated Diseases; Malaria; Malaria, Cerebral - parasitology; Malaria, Cerebral - physiopathology; Medical research; Medical treatment; Mice; Mice, Inbred C57BL; Microbiology/Parasitology; Mortality; Neurological Disorders/Infectious Diseases of the Nervous System; Neuroscience/Neurobiology of Disease and Regeneration; Parasites; Parasitic diseases; Pathogenesis; Pathology; Pathology/Neuropathology; Pediatrics; Pediatrics and Child Health/Pediatric Critical Care; Plasmodium berghei; Plasmodium berghei - isolation & purification; Plasmodium falciparum; Preventive medicine; Public Health and Epidemiology/Infectious Diseases; Seizures; Therapy; Vector-borne diseases; Chicago Illinois; Indiana; United States > US; Illinois
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013124

Cerebral malaria (CM) is a neurological syndrome that includes coma and seizures following malaria parasite infection. The pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to CM, even if the underlying parasite infection has resolved. To that effect, there is no known adjuvant therapy for CM. Current murine CM (MCM) models do not allow for rapid clinical identification of affected animals following infection. An animal model that more closely mimics the clinical features of human CM would be helpful in elucidating potential mechanisms of disease pathogenesis and evaluating new adjuvant therapies. A quantitative, rapid murine coma and behavior scale (RMCBS) comprised of 10 parameters was developed to assess MCM manifested in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA). Using this method a single mouse can be completely assessed within 3 minutes. The RMCBS enables the operator to follow the evolution of the clinical syndrome, validated here by correlations with intracerebral hemorrhages. It provides a tool by which subjects can be identified as symptomatic prior to the initiation of trial treatment. Since the RMCBS enables an operator to rapidly follow the course of disease, label a subject as affected or not, and correlate the level of illness with neuropathologic injury, it can ultimately be used to guide the initiation of treatment after the onset of cerebral disease (thus emulating the situation in the field). The RMCBS is a tool by which an adjuvant therapy can be objectively assessed.