Original articleBrain-Derived Neurotrophic Factor Rescues Neurons From Bacterial Meningitis
Introduction
Bacterial meningitis is a serious infection most commonly occurring in the central nervous system. This disease is fatal in 5-40% of patients, and transient or permanent neurological sequelae including deafness, epilepsy, mental retardation, and the impairment of sensorimotor function, among others, arise in up to a third of survivors [1], [2]. Advanced antimicrobial agents have had a profound effect on the clinical course and prognosis of bacterial meningitis, and outcomes have been modestly improved by advanced medical intensive care technology and the availability of new, effective antibiotics. Further improvements in treatment can only result from a better understanding of the pathophysiological events that occur after activation of the host’s inflammatory responses by either the bacteria or their products, and of the molecular mechanisms that take part in the genesis of brain damage during bacterial meningitis and after initiation of antibiotic treatment [2], [3], [4], [5].
In previous work [6], [7], we found that the expression of brain-derived neurotrophic factor (BDNF) mRNA and its production in the brain, and its receptor, tyrosine kinase receptor B (TrkB), is downregulated after administration of antibiotics in bacterial meningitis, and that there is a dose-dependent downregulation of BDNF by antibiotics, but there is no effect on the expression of BDNF in normal animals treated with antibiotics. That is, the intrinsic neuroprotective role of BDNF was reduced in bacterial meningitis after treatment with antibiotics [6], [7]. The present work uses a rat model of experimental pneumococcal meningitis to study the neuroprotective effects of BDNF on brain injury.
Section snippets
Animals and Cannula Implantation
Forty-four Sprague-Dawley rats were selected, aged 3 weeks. The rats were anesthetized with 0.15-0.3 mL/100 g 10% chloral hydrate injected intraperitoneally. Two stainless steel cannulas were implanted, into the left and right lateral cerebral ventricles, and were located 3.8 mm rostral to the lambdoid suture of the skull, 2 mm lateral on both sides from the midline of the skull, and 2.5 mm from the skull surface [8]. The rats were fostered in their cages for three days.
Experimental Design and BDNF Injection
The 44 rats were
Mortality Rate
During the course of treatment, one rat in group 2 (the control group after infection) and two rats in group 4 (the control group before infection) died of serious meningitis. The mortality was thus 12.5% and 25%, respectively, but there was no significance difference between the two kinds of mortality (P > 0.05). No rats died in groups 1 or 3 (the group treated after or before infection), nor in groups 5 or 6 (the groups treated or control group after injection of normal saline).
Population of Survival Neurons in Cerebral Cortex
Nissl staining
Discussion
Our experiments have confirmed that neurons of the brain were damaged following bacterial meningitis, that the exogenous BDNF could protect a large number of neurons in cortex and hippocampus from inflammatory brain damage in bacterial meningitis, and that the neuroprotective effect did not show significant difference between the treatment of BDNF before and after infection, nor between the normal group treated with BDNF and the normal control group not so treated. The findings suggest that the
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Exogenous BDNF increases neurogenesis in the hippocampus in experimental Streptococcus pneumoniae meningitis
2016, Journal of NeuroimmunologyCitation Excerpt :Several studies have found that decreased levels of hippocampal BDNF are correlated with behavioral deficits (Barichello et al., 2010), and exogenous BDNF could play a neuroprotective role by preventing neuronal death and decreasing the size of the infarction, whereas decreased growth factor expression via inhibitors or in knockout mice impairs neurogenesis (Bifrare et al., 2005; Chen et al., 2005; Kiprianova et al., 1999). In our recent studies, BDNF has been found to play a neuroprotective role via up-regulation of the expression of trkB mRNA, which can consequently rescue the number of neurons; however, its role in the proliferation and differentiation of endogenous NSCs has not been examined (Li et al., 2007; Song et al., 2014). Using immunofluorescence labeling with BrdU and various markers, we hypothesize that BDNF could enhance the neurogenesis of endogenous NSCs at early time after bacterial meningitis.
Targets for adjunctive therapy in pneumococcal meningitis
2015, Journal of NeuroimmunologyCitation Excerpt :BDNF reduces the translocation of AIF, attenuates excitotoxicity of glutamate, and increases the antioxidant activities of enzyme (Bifrare et al., 2005). In another study, the neuronal population in both the cerebral cortex and the hippocampus of rats treated with BDNF was markedly increased (Li et al., 2007). During pneumococcal meningitis, large amounts of superoxide anions (O2−) and nitric oxides (NO) are produced, leading to the formation of peroxynitrite species (ONOO−), as a consequence of oxidative stress (Klein et al., 2006).
Neonatal Escherichia coli K1 meningitis causes learning and memory impairments in adulthood
2014, Journal of NeuroimmunologyCitation Excerpt :Neurons are the main source of BDNF in the CNS (Lewin and Barde, 1996). Furthermore, BDNF secreted by immune cells is bioactive (Kerschensteiner et al., 1999), and it has neuroprotective effects on neurons following bacterial meningitis induction (Li et al., 2007). BDNF protects against multiple forms of brain injury (Bifrare et al., 2005), and may rescue brain neurons from inflammatory brain injury in bacterial meningitis (Li et al., 2007).
Evaluation of the brain-derived neurotrophic factor, nerve growth factor and memory in adult rats survivors of the neonatal meningitis by Streptococcus agalactiae
2013, Brain Research BulletinCitation Excerpt :This neurotrophin is found in several types of neuronal cells and is highly expressed in the hippocampus (Han et al., 2000), evidence indicate that BDNF is essential in sustaining physiological processes of the normal, intact adult brain, and also has a role in synaptic plasticity and long-term potentiation (Kang, 1995), with this manner it influences learning and memory (Yamada et al., 2002). Moreover, Li et al. (2007) demonstrated that BDNF could protect a large number of neurons in cerebral cortex and hippocampus from inflammatory brain injury in bacterial meningitis, one previous study also showed that BDNF blocked the caspase-3 activation in neonatal hipoxia-ischemia (Han et al., 2000). Caspase-3 mediated hippocampal apoptosis in pneumococcal meningitis (Gianinazzi et al., 2003) and when its activation was inhibited it also decreased neurological sequelae in animal induced with GBS meningitis (Irazuzta et al., 2008).
Correlation between behavioral deficits and decreased brain-derived neurotrofic factor in neonatal meningitis
2010, Journal of Neuroimmunology