Radiological, biomechanical and histopathological characteristics of rat brain in Kaolin-induced hydrocephalus

Objective: A better understanding of the pathophysiology and underlying mechanisms of brain damage in hydrocephalus is vital in developing diagnostic, observational and treatment tools that will have an impact on hydrocephalus outcomes. In this study, we aimed to demonstrate the radiological, biomechanical and histopathological characteristics of rat brain tissue in an experimental hydrocephalus model. Materials and Methods: Thirty-six male Sprague-Dawley rats (21 days old, weighing between 150 and 200 grams) were used in this study. Animals were randomly assigned to control (n = 6), 1-week hydrocephalus (n = 10), 2-week hydrocephalus (n = 10) and 3-week hydrocephalus (n = 10) groups. Hydrocephalus was induced with cisternal kaolin injection and controls received sham injection. Magnetic resonance imaging was used to measure ventricle size and cortical thickness. Vital signs, cerebral blood flow (CBF), mechanical tests and brain histology were assessed. Results: Three rats in the hydrocephalus group died during the follow-up, yielding an overall mortality of 10% among animals from hydrocephalus groups. Ventricular width, cross-sectional area of the lateral ventricles, ventricular index and ventricle / brain area ratio progressively increased and cortical thickness progressively decreased following kaolin injection. CBF was significantly lower at baseline than at 1st, 2nd and 3rd week (p < 0.05, for all). ICP was significantly elevated in all hydrocephalic groups in comparison with controls. EIT that was calculated from the first load-unload indentation test showed a significant increase at 2nd week post-injection (p=0.0001), indicating increased intracranial stiffness. However, this significant difference disappeared at 3rd week (p=0.956). Quantitative immunohistochemistry showed that hydrocephalic brains demonstrated significantly less NeuN-positive cells and significantly higher IBA-1-positive microglia and glial fibrillary acidic protein positive astrocytes cells in the cortex. Discussion and Conclusion: Cisternal kaolin injection causes varying degrees of ventricular enlargement in a rat model and hydrocephalus might contribute to neuronal and axonal damage and alter brain stiffness through axonal stretching or local hypoperfusion progressively over a period of days to months. As shown in this study, irreversible changes in viscoelastic behaviour and cellular structure develop in the late stages of hydrocephalus, suggesting the importance of early intervention in the treatment of hydrocephalus.

211 Macromolecular Clearance from the Ventricles by Choroid Plexus in Experimental Hydrocephalus

INTRODUCTION Choroid plexus is known to be the source of cerebrospinal fluid and therefore, has been the target of surgical destruction or coagulation in the treatment of hydrocephalus. The role of choroid plexus in the homeostasis of the cerebrospinal fluid is unclear in the presence of hydrocephalus. METHODS We performed experiments to study the distribution and kinetics of iron labeled dextran in rats using a 7T MRI scan for a period of two hours during and immediately following injection. Rats were randomly divided into three groups: normal (n = 9), communicating hydrocephalus induced by kaolin (n = 11) and obstructive hydrocephalus induced by kaolin (n = 4). Presence of iron tagged dextran in the choroid plexus was determined as a change in the MRI signal (decreased T2 value) and histology after sacrifice of the animals. RESULTS >MR data was measured at three different time points: preinjection, 35 minutes post and 79 minutes post injection. We found that in all groups there was uptake of iron tagged dextran into the choroid plexus. While the T2 vlaues of CP returned baseline at 79 minutes in normal, while these values were still far below the baseline in kaolin induced hydrocephalus groups and these were statistically significant (P < 0.05). Normal rat, CP T2 values 101 ± 5(n = 18) (pre), 64 ± 1(35m post), 92 ± 1 (79m post). Hy-BC rat, CP T2 values 148 ± 26(n = 76) (pre), 60 ± 4(35m post), 71 ± 8(79m post). Hy-CM rat, CP T2 values156± 32(n = 53) (pre), 39 ± 6(35m post), 35 ± 4(79m post). Histopathology confirmed the presence of dextrans in the choroid plexus. Spectrophotometric assay of serum and urine revealed that dextrans were detected in both with a peak in the serum at 30 mins and peak in the urine at 45 mins. CONCLUSION Choroid plexus plays a beneficial role in the clearance of macromolecules from the CSF in both normal and hydrocephalic states.