Brain-derived neurotrophic factor protects against multiple forms of brain injury in bacterial meningitis.
BACKGROUND
Brain-derived neurotrophic factor (BDNF) blocks activation of caspase-3, reduces translocation of apoptosis-inducing factor (AIF), attenuates excitotoxicity of glutamate, and increases antioxidant enzyme activities. The mechanisms of neuroprotection suggest that BDNF may be beneficial in bacterial meningitis.


METHODS
To assess a potentially beneficial effect of adjuvant treatment with BDNF in bacterial meningitis, 11-day-old infant rats with experimental meningitis due to Streptococcus pneumoniae or group B streptococci (GBS) were randomly assigned to receive intracisternal injections with either BDNF (3 mg/kg) or equal volumes (10 mu L) of saline. Twenty-two hours after infection, brains were analyzed, by histomorphometrical examination, for the extent of cortical and hippocampal neuronal injury.


RESULTS
Compared with treatment with saline, treatment with BDNF significantly reduced the extent of 3 distinct forms of brain cell injury in this disease model: cortical necrosis in meningitis due to GBS (median, 0.0% [range, 0.0%-33.7%] vs. 21.3% [range, 0.0%-55.3%]; P<.03), caspase-3-dependent cell death in meningitis due to S. pneumoniae (median score, 0.33 [range, 0.0-1.0] vs. 1.10 [0.10-1.56]; P<.05), and caspase-3-independent hippocampal cell death in meningitis due to GBS (median score, 0 [range, 0-2] vs. 0.88 [range, 0-3.25]; P<.02). The last form of injury was associated with nuclear translocation of AIF.


CONCLUSIONS
BDNF efficiently reduces multiple forms of neuronal injury in bacterial meningitis and may hold promise as adjunctive therapy for this disease.
Bifrare
Yoeng-Delphine
YD
Institute for Infectious Diseases, University of Bern, 3010 Bern, Switzerland.
Kummer
Jürg
J
Joss
Philipp
P
Täuber
Martin G
MG
Leib
Stephen L
SL
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D001921:Brain / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D002540:Cerebral Cortex / Q000473:pathology; D004195:Disease Models, Animal; D005420:Flavoproteins / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000473:pathology*; D008586:Meningitis, Pneumococcal / Q000188:drug therapy / Q000473:pathology; D009336:Necrosis / Q000517:prevention & control; D051381:Rats; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000473:pathology*; D013292:Streptococcus agalactiae; D013296:Streptococcus pneumoniae
C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D019208:Brain-Derived Neurotrophic Factor; D005420:Flavoproteins; D008565:Membrane Proteins