IMPAIRED NEONATAL CEREBRAL BLOOD FLOW AUTOREGULATION IN GROUP B STREPTOCOCCAL MENINGITIS IS NOT MEDIATED BY TUMOR NECROSIS FACTOR (TNFα).• 977

Abstract

Group B streptococcal (GBS) meningitis impairs cerebral blood flow (CBF) autoregulation in newborn piglets probably via inflammatory mediators in response to GBS. We tested whether TNFα mediates early CBF impairment by GBS in 3 grps of awake sedated newborn piglets (0-5 days). Grp 1 (CTRL), n=8 had normal saline (0.5ml) via the lateral cerebral ventricle (icv), Grp 2(n=7) had heat killed unencapsulated GBS (109 cfu, 0.5ml icv) and Grp 3 had TNFα, 1,000 units icv, 0.5ml). CBF was measured over a range of mean arterial blood pressure (35-125 mmHg) induced by inflating balloon tipped catheters at the aortic root to produce cerebral hypotension or descending aorta for hypertension at 5 time points: 15 min pre (baseline) and post injection of either saline, GBS or TNFα), and during randome hypo-, normo-, and hypertension. RESULTS: 1) Grp 1, CBF and CPP (cerebral perfusion pressure) best fitted a 3rd order polynomial regression (R2=0.57,p=0.008) with constant CBF at 50-90 mmHg CPP. 2) Grp 2, GBS caused direct correlation in CBF and CPP (50-110 mmHg), r=0.52, p <0.05. Grp 3 (TNFα) had CBF constant at 50-110 mmHg, r=0.12, p=NS. Cerebrovascular resistance correlated with CPP(50-125 mmHg) in CTRL (r=0.458,p=0.009)and TNFα grps (r=0.60, p=0.002) but not in GBS grp (r=0.06, p=.8). Thus, TNFα did not mediate early impairment in neonatal CBF autoregulation in GBS meningitis and therapies directed to TNFα may not correct CBF changes.Figure