NEUTROPENIA PRESERVES ENERGY METABOLITES DURING CEREBRAL HYPOXIA-ISCHEMIA IN THE NEONATAL RAT. † 2256

Abstract

We found that neutropenia induced before cerebral hypoxia-ischemia (HI) in the 7day old rat is neuroprotective. However, neutrophil depletion achieved by 6-8hrs of recovery is not protective. Neutrophils can plug microvessels and reduce red cell velocity when flow is reduced during ischemia. The aims of this study were to determine the effect of neutropenia on cerebral energy metabolism during the HI insult and at 6hrs of recovery. We produced a HI insult to the R cerebral hemisphere (RH) of 7day old rat pups by R common carotid artery ligation and 2.25h hypoxia in 8% oxygen. This insult causes cerebral ischemia and injury to the right hemisphere. We made some rats neutropenic with antineutrophil serum before HI. Other rats received normal rabbit serum as control. Sixteen rats of each group were killed by immersion in liquid nitrogen at the end of the HI insult and 10-12 of each group at 6h of recovery from HI. From perchloric acid brain extracts we measured L and R hemisphere levels of P-Cr, ATP, ADP, AMP, and calculated Total Adenine Nucleotides (TAN). We compared the energy metabolite levels of the neutropenic and nonneutropenic rats at 0 and 6h recovery. Normal levels of ATP were 2.29±0.18mmol/kg (Mean ±SD). In the nonneutropenic rats at 0 recovery ATP levels were 0.88±.59 while in the neutropenic rats it was 1.3±0.76. Seven of 16 neutropenic rats had ATP levels at 0 recovery within 3SD of normal compared to only 2 of 14 nonneutropenic rats, p=.04 Chi Square. TAN levels were 2.7±0.22 in the normal rats, at 0h recovery they were 2.02±0.56 mmol/kg in neutropenic rats and only 1.55±0.56 in the nonneutropenic rats, p =0.02 Mann-Whitney U test. At 6 hours of recovery ATP levels had returned to within 2SD of the Mean(1.93-2.65mmol/kg) in all 12 neutropenic rats and 7/10 nonneutropenic rats. There was not a significant difference between the neutropenic and nonneutropenic rats at 6hrs of recovery for any metabolite. Average levels were normal for all metabolites at 6h recovery. In conclusion neutropenia induced before cerebral HI preserves energy metabolism during the insult. Cerebral energy metabolism recovers by 6 hrs of recovery following a hypoxic ischemic insult.