Behavioral and Biochemical Features of the Course and Surgical Treatment of Experimental Obstructive Hydrocephalus in Young Rats

Abstract

Introduction: Hydrocephalus is a multifactorial disease, affecting the dynamics of cerebrospinal fluid (CSF) and leading to severe neurological impairment in children; in spite of the recent advances in hydrocephalus research, it has many physiopathological aspects that still remain poorly understood, especially after treatment. Objectives: To analyze the clinical, radiological, histopathological, and biochemical aspects of kaolin-induced hydrocephalus in an experimental model, both in the acute phase and after shunt treatment, by means of behavioral tests, magnetic resonance imaging (MRI) scans, histopathological studies, and level of inflammatory interleukins in the CSF. Methods: Seven-day-old Wistar rats were used and subdivided into three subgroups: treated hydrocephalic (n = 24), untreated hydrocephalic (n = 17), and controls (n = 5). The hydrocephalic groups underwent cisternal injection of 15% kaolin for induction of hydrocephalus at 7 days of age. The treated group was submitted to a ventricular-subcutaneous shunt (VSCS) 1 week after induction. All animals were euthanized at 21 days of age. They underwent motor function and memory testing as well as brain MRI scans. Histopathological analysis for glial fibrillary acidic protein and Ki-67 was done, and CSF was collected for measurement of IL-1β, IL-6, and TNF-α. Results: The average time to reach the water maze platform was highest in the untreated hydrocephalic group. The magnetization transfer rates were 37.21 and 33.76 before and after shunting, respectively. The mean astrocyte counts were 2.45, 1.36, and 90.5 for shunted, untreated, and control animals, respectively. The mean CSF IL-1β concentrations were 62.3 and 249.6 pg/mL, the average IL-6 levels were 104.2 and 364.7 pg/mL, and the average TNF-α values were 4.9 and 170.5 pg/mL for the treated hydrocephalic group and the untreated group, respectively. Conclusions: Pups treated with a CSF shunt showed better performance on memory tests. VSCS did not revert demyelination caused by hydrocephalus. Likewise, reactive astrocytosis and cell proliferation over the germinal matrix were not reversed after shunting. Hydrocephalic animals had raised levels of inflammatory interleukins, which returned to normal after treatment.

Memory deficits in Sprague Dawley rats with spontaneous ventriculomegaly

“…Animal models of neonatal hydrocephalus and ventriculomegaly exist (McAllister 2012; Volpon Santos, da Silva Lopes, Machado, & Santos de Oliveira, 2019). In this work we report similar anatomical findings, such as paper‐thin cerebral cortex and greatly enlarged brain ventricular system, as an incidental finding, not induced by any genetic or mechanical process.…”

Effects of Cerebrospinal Fluid Drainage on Pro-Inflammatory and Anti-Inflammatory Cytokines Expression in the Subventricular Zone of Kaolin-Induced Hydrocephalic Rats

“…The anatomical landmark in our study is located 1 cm anterior and 1 cm lateral to the bregma, with a depth of approximately 1.5 cm perpendicular to the bone. 11…”