RGD Reference Report - Inhibition of matrix metalloproteinases-2 and -9 prevents cognitive impairment induced by pneumococcal meningitis in Wistar rats. - Rat Genome Database

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Inhibition of matrix metalloproteinases-2 and -9 prevents cognitive impairment induced by pneumococcal meningitis in Wistar rats.

Authors: Barichello, T  Generoso, JS  Michelon, CM  Simoes, LR  Elias, SG  Vuolo, F  Comim, CM  Dal-Pizzol, F  Quevedo, J 
Citation: Barichello T, etal., Exp Biol Med (Maywood). 2014 Feb;239(2):225-31. doi: 10.1177/1535370213508354. Epub 2014 Jan 13.
RGD ID: 8657111
Pubmed: PMID:24419461   (View Abstract at PubMed)
DOI: DOI:10.1177/1535370213508354   (Journal Full-text)

Pneumococcal meningitis is a relevant clinical disease characterized by an intense inflammatory reaction into the subarachnoid and ventricular spaces, leading to blood-brain barrier breakdown, hearing loss, and cognitive impairment. Matrix metalloproteinases (MMPs) are capable of degrading components of the basal laminin, thus contributing to BBB damage and neuronal injury. In the present study, we evaluated the effects of MMP-2, MMP-9, and MMP-2/9 inhibitors on BBB integrity, learning, and memory in Wistar rats subjected to pneumococcal meningitis. The animals underwent a magna cistern tap and received either 10 microL sterile saline as a placebo or an equivalent volume of a Streptococcus pneumoniae suspension at a concentration of 5 x 10(9)cfu/mL. The rats were randomized into different groups that received adjuvant treatment with MMP-2, MMP-9 or MMP-2/9 inhibitors. The BBB integrity was evaluated, and the animals were habituated to open-field and object recognition tasks 10 days after meningitis induction. Adjuvant treatments with inhibitors of MMP-2 or MMP-2/9 prevented BBB breakdown in the hippocampus, and treatments with inhibitors of MMP-2, MMP-9 or MMP-2/9 prevented BBB breakdown in the cortex. Ten days after meningitis induction, the animals that received adjuvant treatment with the inhibitor of MMP-2/9 demonstrated that animals habituated to the open-field task faster and enhanced memory during short-term and long-term retention test sessions in the object recognition task. Further investigation is necessary to provide support for MMP inhibitors as an alternative treatment for bacterial meningitis; however, these findings suggest that the meningitis model could be a good research tool for studying the biological mechanisms involved in the behavioral alterations associated with pneumococcal meningitis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Pneumococcal Meningitis treatmentISOMmp2 (Rattus norvegicus)8657111; 8657111 RGD 
Pneumococcal Meningitis treatmentISOMmp9 (Rattus norvegicus)8657111; 8657111 RGD 
Pneumococcal Meningitis treatmentIMP 8657111; 8657111 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp2  (matrix metallopeptidase 2)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp2  (matrix metallopeptidase 2)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP2  (matrix metallopeptidase 2)
MMP9  (matrix metallopeptidase 9)


Additional Information