TUMOR-NECROSIS-FACTOR-ALPHA CONTRIBUTES TO APOPTOSIS IN HIPPOCAMPAL-NEURONS DURING EXPERIMENTAL GROUP-B STREPTOCOCCAL MENINGITIS

To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) in neu ronal injury in experimental group B streptococcal meningitis, infecte d neonatal rats were treated with a monoclonal antibody against TNF-al pha (20 mg/kg intraperitoneally) or saline given at the time of infect ion. Histopathology after 24 h showed necrosis in the cortex and apopt osis in the hippocampal dentate gyrus. Treated animals had significant ly less hippocampal injury than did controls (P < .001) but had simila r cortical injury and cerebrospinal fluid (CSF) inflammation. The anti body was then administered directly intracisternally (170 mu g) to tes t whether higher CSF concentrations reduced inflammation or cortical i njury. Again, hippocampal apoptosis was significantly reduced (P < .01 ), while cortical injury and inflammation were not. Thus, TNF-alpha pl ayed a critical role in neuronal apoptosis in the hippocampus, while i t was not essential for the development of inflammation and cortical i njury in this model.