Effect of intracerebral infusion rate on optic nerve tissue pressure and diurnal intracranial pressure in rats

To characterize how optic nerve tissue sheath (ONSp) responds to changes in intracerebral fluid infusion rate and consider if low rate intracerebral ventricular (ICV) infusion changes diurnal intracranial pressure (ICP) in rats. Anesthetized adult male rats underwent cannula placement into the lateral ventricles, for infusion and ICP monitoring. ICV infusion rate controlled ICP. A second syringe pump delivered sodium fluorescein for quantification of cerebrospinal fluid (CSF) flow to the optic nerve with fluorescence imaging (n = 14). Cannula were placed in lateral ventricle and under the optic nerve sheath (n = 6) for simultaneous pressure measurement at different ICV infusion rates, and at normal (n = 6, 95.6 ± 5.9mmHg) or high blood pressure (n = 4, 158.0 ± 9.5mmHg, intravenous Angiotensin II). Four rats were implanted with sub-dural sensors for awake ICP monitoring. Animals had ICV infusion of sterile saline at a low rate (2.5 ml/hr) for the first 4 weeks followed by a high rate (10 ml/hr) for week 5. Higher ICV flow rates produce predictable increases in ICP, which result in an increased ONSp. CSF pressure was 73 ± 3% lower at the optic nerve sheath compared with the lateral ventricle (ONSp = 0.71*ICP-5.69). At normal blood pressure, average ICP was 15.5 ± 0.4mmHg and ONSp was 3.2 ± 0.6mmHg. At high blood pressure, ICP increased to 16.8 ± 4.5mmHg and ONSp was 4.2 ± 4.4mmHg. For the chronic study, mean ICP levels were stable across the 5 weeks, however peak ICP was increased particularly during nocturnal hours. Changes in rat ICP directly change ONSp in a predictable manner. Chronic low volume ICV fluid infusion does not substantially increase rat ICP.