Exploring the Relationship of Varying Hydrocephalus Severity on CSF Dynamics in a Pediatric Hydrocephalus Rodent Model

Introduction: Hydrocephalus often culminates in deleterious neurological effects and high intracranial pressure in the pediatric condition. Studies observing the relationship between intracranial pressure and cerebrospinal fluid (CSF) production in an electrical resistance model have been performed, but less has been done to define this relationship in living organisms. This study explored how CSF flow dynamics change as a consequence of hydrocephalus severity utilizing a new model.

Methods: A novel model was employed in which rats’ hydrocephalus was induced through administration of 30-50 micrometers of 25% (w/v) kaolin to obstruct CSF outflow through the cisterna magna. After a 15-16 day acclimation, the rats were anesthetized with isoflurane. A Transonic SP200 pressure transducer was surgically inserted into the femoral artery and advanced to the thoracic aorta to measure mean arterial pressure, heart rate, contractility index, and pulse height. While maintaining the probe, a craniotomy was performed and CSF flow was measured via Sensiron SLI 0430 simultaneously to the measure of cardiac variables. Rats were then euthanized for investigation of the degree of ventriculomegaly by Evan’s Ratio of the whole brain. The hydrocephalic ventricles were compared to control rats that had CSF flow obstructed only immediately before CSF flow measurements in order to direct CSF flow towards the probe.

Results: The Evan’s Ratio as a measure of hydrocephalus severity was compared to each specific variable measured to see if there were clear linear relationships. After analysis, there were no significant relationships observed between Evan’s Ratio and CSF flow (R2=0.182; n=12).

Conclusion : The data indicates that Evan’s Ratio does not exhibit a linear relationship with CSF flow. This model was useful in the measurements of CSF flow and cardiac function, but further exploration of non-linear or multi-regression relationships that influence CSF flow in the setting of hydrocephalus is warranted. Confounding variables such as probe placement and environmental conditions, may have had impacts on outcomes, also requiring additional control in the future.