Abstract
BackgroundThe central nervous system (CNS) is extremely vulnerable to ischemic injury. The details underlying this susceptibility are not completely understood. Since the CNS is surrounded by cerebrospinal fluid (CSF) that contains a low concentration of plasma protein, we examined the effect of changing the CSF in the evolution of CNS injury during ischemic insult.MethodsLumbar spinal cord ischemia was induced in rabbits by cross-clamping the descending abdominal aorta for 1 h, 2 h or 3 h followed by 7 d of reperfusion. Prior to ischemia, rabbits were subjected to the following procedures; 1) CSF depletion, 2) CSF replenishment at 0 mmHg intracranial pressure (ICP), and 3) replacement of CSF with 8% albumin- or 1% gelatin-modified artificial CSF, respectively. Motor function of the hind limbs and histopathological changes of the spinal cord were scored. Post-ischemic microcirculation of the spinal cord was visualized by fluorescein isothiocyanate (FITC) albumin.ResultsThe severity of histopathological damage paralleled the neurological deficit scores. Paraplegia and associated histopathological changes were accompanied by a clear post-ischemic deficit in blood perfusion.Spinal cord ischemia for 1 h resulted in permanent paraplegia in the control group. Depletion of the CSF significantly prevented paraplegia. CSF replenishment with the ICP reduced to 0 mmHg, did not prevent paraplegia. Replacement of CSF with albumin- or gelatin-modified artificial CSF prevented paraplegia in rabbits even when the ICP was maintained at 10–15 mmHg.ConclusionWe conclude that the presence of normal CSF may contribute to the vulnerability of the spinal cord to ischemic injury. Depletion of the CSF or replacement of the CSF with an albumin- or gelatin-modified artificial CSF can be neuroprotective.
Highlights
The central nervous system (CNS) is extremely vulnerable to ischemic injury
Control animals subjected to 1 h of spinal cord ischemia demonstrated permanent paraplegia (100% paraplegic rate, Fig. 1A, group 1-closed circles)
The cerebrospinal fluid (CSF) depletion with the intracranial pressure (ICP) maintained at 0 mmHg prevented the development of paraplegia (0% paraplegic rate, Fig. 1A, group 2-open circles)
Summary
Lumbar spinal cord ischemia was induced in rabbits by cross-clamping the descending abdominal aorta for 1 h, 2 h or 3 h followed by 7 d of reperfusion. Rabbits were subjected to the following procedures; 1) CSF depletion, 2) CSF replenishment at 0 mmHg intracranial pressure (ICP), and 3) replacement of CSF with 8% albumin- or 1% gelatin-modified artificial CSF, respectively. To facilitate removal of the CSF and to administer albumin- and gelatin-modified artificial CSF another silicon tube was placed in the lumbar subarachnoid space. A laminectomy was carried out at sacrococcygeal level to expose the lumbar subarachnoid space. The tube was twisted gently into subarachnoid space through the dura and immobilized with the same adhesive to the adjacent muscle
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