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Mechanisms of Action of Mannitol in Lowering of CSF Pressure

Background and purpose: Hyperosmolar mannitol is used for treatmentof intracranial hypertension but mechanism how it lowers the cerebrospinal (CSF) pressure is still controversial. After application of mannitol the CSF pressure is usually lowered within 30 min but this effect cannot be explained either by changes in intracranial blood volume and flow or by changes in volume of both intra- and extracellular fluid in tissue of the central nervous system (CNS). We assume that after intravenous application of mannitol an osmotic gradient across the blood-brain barrier is generated with consequente osmotic "suction" of water from extracellular space is replaced by water coming from CSF. Since cranial dura is closely attached to bones, in contrast to spinal dura wich is relatively free and compliant, we suppose that water in CNS extracellular space is replaced by water originating from spinal CSF with consequent fall of CSF pressure. Materials and Methods: To explore such a possibility we planned to separate spinal and cerebral CSF. In chloralose anaesthetized cats the dorsal laminectomy of C2 vertebrae was performed and a plastic semiring was positioned extradurally separating cranial and spinal CSF. CSF pressure were recorded via cannulas positioned in both lateral ventricle and lumbar subarachnoid space at L3 vertebrae, respectively. Results: After position of plastic semiring the CSF pressures transiently increased but soon returned to normal value without development of any significant pressure gradient between ventricular and lumbar CSF over next 60 min. When CSF pressure was increased by infusion of mock CSF into lateral ventricle and than mannitol applied intravenously (1.0 g/kg over 3 min) ventricular and lumbar CSF pressure fall over next 10 min, but therafter the ventricular CSF pressure remained constant while lumbar CSF pressure continued to fall creating a gradient of CSF pressure of 7 to 9 cm H2O. However, after removal of cervical stenosis these gradients disappeared. Conclusion: The obesved changes of CSF pressure in separated spinal and intracranial spaces after application of hyperosmolar mannitol indicate that CSF absorption and decrease of spinal CSF volume are mainly responsible for overall of CSF pressure inside craniospinal space.

mannitol ; intracranial pressure ; cervical stenosis ; spinal dura compliance

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