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A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation
Published on: June 10, 2020
Cerebrospinal fluid may mediate CNS ischemic injury
Yanming F Wang1, Judith K Gwathmey, Guorong Zhang
1Neuroprotection Inc., 100 Cummings Center, Beverly, MA 01915, USA. yanming.wang@childrens.harvard.edu
Cerebrospinal Fluid Research
|September 22, 2005
Summary
Altering cerebrospinal fluid (CSF) composition can protect the spinal cord from ischemic injury. Modifying CSF with albumin or gelatin prevented paralysis in rabbits, suggesting a neuroprotective role for CSF alteration in CNS injury.
Area of Science:
- Neuroscience
- Ischemic Injury Research
- Cerebrospinal Fluid Dynamics
Background:
- The central nervous system (CNS) exhibits high susceptibility to ischemic injury, with underlying mechanisms not fully elucidated.
- Cerebrospinal fluid (CSF), characterized by low plasma protein concentration, surrounds the CNS, potentially influencing injury progression.
Purpose of the Study:
- To investigate the impact of altering cerebrospinal fluid (CSF) composition on the severity of CNS injury during ischemic events.
- To evaluate the neuroprotective potential of CSF depletion or modification with protein-containing artificial CSF.
Main Methods:
- Induction of lumbar spinal cord ischemia in rabbits via aortic cross-clamping for 1-3 hours, followed by 7 days of reperfusion.
- Experimental groups included CSF depletion, CSF replenishment at 0 mmHg intracranial pressure (ICP), and replacement with artificial CSF (8% albumin or 1% gelatin).
- Assessment of hind limb motor function, spinal cord histopathology, and post-ischemic microcirculation using FITC-albumin.
Main Results:
- Histopathological damage and neurological deficits correlated directly, with 1-hour ischemia causing permanent paraplegia in controls.
- CSF depletion significantly mitigated paraplegia.
- Replacing CSF with albumin- or gelatin-modified artificial CSF prevented paraplegia, even at elevated ICP levels (10-15 mmHg).
Conclusions:
- Normal cerebrospinal fluid (CSF) may exacerbate spinal cord vulnerability to ischemic injury.
- Depleting CSF or substituting it with albumin- or gelatin-modified artificial CSF demonstrates significant neuroprotective effects against ischemic damage.
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