Modulation of Hippocampal Neuroplasticity by Fas/CD95 Regulatory Protein 2 (Faim2) in the Course of Bacterial Meningitis

Tauber, Simone C.; Harms, Kristian; Falkenburger, Björn H.; Weis, Joachim; Sellhaus, Bernd; Nau, Roland; Schulz, Jörg B.; Reich, Arno

doi:10.1097/nen.0000000000000020

Cited by 19 publications

(33 citation statements)

References 55 publications

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“…A number of studies have demonstrated that neurons in the CNS undergo apoptotic cell death during SP-induced bacterial meningitis (20)(21)(22)(23). Consistent with this, the B7-H3-amplified cell apoptosis and neuronal loss as demonstrated by TUNEL and Nissl staining in the present study are also associated with deteriorated clinical disease status.…”

Section: Discussionsupporting

confidence: 78%

B7 homolog 3 aggravates brain injury in a murine model of Streptococcus pneumoniae-induced meningitis

Chen

Wang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Despite the application of antibiotics, Streptococcus pneumoniae (SP)-induced meningitis continues to be a life-threatening disease with a high fatality rate and an elevated risk of serious neurological sequelae, particularly in developing countries. In this study, the contribution of the co-stimulatory molecule B7 homolog 3 (B7-H3) to the pathogenesis of experimental SP-induced meningitis was investigated. Mice were challenged with the intracerebroventricular injection of serotype 3 SP with or without B7-H3. The clinical status of mice with SP-induced meningitis was examined by body weight loss and spontaneous motor activity with neurological scoring. Coronal brain sections were analyzed by counting Nissl-positive neurons and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells. Protein expression of neuron-specific enolase (NSE) and S100B in brain tissues was examined with immunohistochemical staining. All experiments were performed in a randomized and blinded setting. By the intracerebroventricular injection of SP suspension, a murine model of pneumococcal meningitis was successfully established. In this SP-induced meningitis model, B7-H3 deteriorated the clinical status, as manifested by a decreased neurological score and increased body weight loss. Following the B7-H3 challenge, the number of Nissl-positive cells decreased and TUNEL-stained positive cells increased in the brain tissues of mice with SP meningitis, which demonstrates the enhancement of neuronal necrosis and apoptosis, respectively. Protein expression of NSE was decreased, while that of S100B was increased. These in vivo findings indicate that B7-H3 aggravates brain injury during the pathological process of experimental SP-induced meningitis. IntroductionDespite treatment with effective antibiotics, Streptococcus pneumoniae (SP) meningitis remains a serious infectious disease of the central nervous system (CNS) with mortality rates between 16 and 37% (1) and neurological sequelae in up to 30% of survivors (2). Therefore, further study of the pathological mechanisms of SP meningitis and the identification of new means of intervention has a great clinical significance. SP-induced meningitis can cause disruption of the blood-brain barrier (BBB), and most severely it can result in brain damage, which affects the prognosis of patients with SP meningitis. Emerging studies have demonstrated that necrosis and apoptosis of brain neurons occur while brain damage is taking place. Neuron-specific enolase (NSE) and S100B have been confirmed to be specific markers of brain damage (3). B7 homolog 3 (B7-H3) is a newly identified member of the B7 superfamily, which serves a key function in the regulation of immune responses (4). Our previous study (5) found an abnormally high expression level of soluble B7-H3 (sB7H3) protein in children with bacterial meningitis. In a murine model of SP-induced meningitis, we also demonstrated that B7-H3 further augmented the inflammatory response, exacerbated BBB disruption, a...

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Section: Discussionsupporting

confidence: 78%

B7 homolog 3 aggravates brain injury in a murine model of Streptococcus pneumoniae-induced meningitis

Chen

Wang

et al. 2015

Experimental and Therapeutic Medicine

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“…This was associated with an improved performance of Fas-apoptotic inhibitory molecule 2-deficient mice compared to wild-type infected mice in the Morris water maze. Thus, inhibition of Fas-apoptotic inhibitory molecule 2 during resolution of inflammation may be able to stimulate neurogenesis and improve cognitive deficits after bacterial meningitis [212]. G-CSF as an adjuvant to ceftriaxone treatment increased hippocampal neurogenesis and improved spatial learning performance 6 weeks after meningitis in a mouse model of Str.…”

Section: Rehabilitationmentioning

confidence: 98%

Bacterial meningitis: an update of new treatment options

Nau

Djukic

Spreer

et al. 2015

Expert Review of Anti-infective Therapy

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The outcome of bacterial meningitis critically depends on the rapid initiation of bactericidal antibiotic therapy and adequate management of septic shock. In community-acquired meningitis, the choice of an optimum initial empirical antibiotic regimen depends on the regional resistance patterns. Pathogens resistant to antibacterials prevail in nosocomial bacterial meningitis. Dexamethasone is recommended as adjunctive therapy for community-acquired meningitis in developed countries. In comatose patients, aggressive measures to lower intracranial pressure <20 mmHg (in particular, external ventriculostomy, osmotherapy and temporary hyperventilation) were effective in a case-control study. Although many experimental approaches were protective in animal models, none of them has been proven effective in patients. Antibiotics, which are bactericidal but do not lyse bacteria, and inhibitors of matrix metalloproteinases or complement factor C5 appear the most promising therapeutic options. At present, vaccination is the most efficient method to reduce disease burden. Palmitoylethanolamide appears promising to enhance the resistance of the brain to infections.

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“…We found more neurogenesis (BrdU positive neurons) in the hippocampus 8 weeks after pneumococcal infection, improved learning after meningitis, and more pronounced sprouting 90 days after MPTP intoxication 3,4 . These findings are consistent with the now established role of Fas/CD95 for regenerative processes, including proliferation and differentiation of neuronal precursors and neurite outgrowth 30,24,31 .…”

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confidence: 83%

“…Similarly, cell death following bacterial meningitis is not primarily mediated by bacterial invasion, but by the inflammatory response that follows infection 3 . Finally, neurons in Parkinson disease and in the applied subacute MPTP model die by an apoptotic mechanism with contributions from excitotoxicity, oxidative stress and inflammation 18,19 .…”

mentioning

confidence: 99%

“…We have investigated the role of one such mudulator, Fas inhibitory molecule 2 (Faim2), in neurologic diseases. We generated a Faim2 deficient mouse line and applyed models of transient cerebral ischemia, bacterial meningitis, and Parkinson disease [2][3][4] . In brief, we found increased neuronal cell death in the acute phase of all disease models in Faim2 deficient mice in comparison to the Faim2 wildtype (WT).…”

mentioning

confidence: 99%

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