Long-Term Infusion of Nonphysiologic Solutions into Brain Parenchyma: Effects of pH, Osmolarity, and Flow Rate

The effects of long-term (3-day) infusion of nonphysiologic solutions into brain parenchyma were inves- tigated in male Fischer (F344) 344 rats. Two weeks prior to infusion, a guide cannula was placed into the striatum, substantia nigra, or hippocampus. Solutions were infused continually for 3 days at flow rates of 0.03 (129.6 l total) or 0.10 (432 l total) l/min. Four days after infusion, rats were euthanized and the brain was removed and processed for histologic evaluation. Rats that received cannula implants alone had the usual mechanical damage induced by implantation of the cannula. The brain regions that received 0.9% saline, pH 5.0 or pH 9.0 buffer at the two aforementioned flow rates had only minor evidence of tissue damage adjacent to the infusion site that was similar to that attributable to mechanical damage from the cannula implants. Brain tissue infused with distilled water or 1.8% saline also had modest effects of the solutions similar to the usual mechanical damage induced by the infusion cannulae. In contrast, contamination of the infusion sites was seen to induce inflammation. Data from these studies support the hypothesis that nonphysiologic solutions can be used to deliver compounds into brain parenchyma, without the infusion solutions themselves causing excess damage to brain tissue.