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A rodent model of experimental posthemorrhagic ventricular dilatation

Presented at the Neonatal Society 2007 Summer Meeting (programme).

Abraham RG, Yasha TC, Sampath S

National Institute of Mental Health & Neuro Sciences, Bangalore, India

Background: Hydrocephalus following intraventricular hemorrhage (IVH) is a major complication of premature birth. Ventriculoperitoneal shunt surgery is difficult in infants and shunts are associated with several serious complications. It is known that fibrosing arachnoiditis, meningeal fibrosis and subependymal gliosis follows IVH. These impair the flow and resorption of cerebrospinal fluid and causes communicating hydrocephalus.

Aim: To produce post hemorrhagic ventricular dilatation (PHVD) in a rodent model of IVH to study the molecular mechanisms involved in the causation of hydrocephalus.

Materials & Methods: 8, 1 month old Sprague Dawley rats (litter mates) weighing approximately (150 g.) were used in this study.

Anesthesia was induced with intraperitoneal injection of Ketamine (70mg/Kg ) and Xylazine (7mg/Kg).

Rats were immobilized in a David Kopf stereotactic apparatus. A single injection of 0.2 ml of heparinised rat blood was administered over 5 minutes (approximate) into the right lateral ventricle. The stereotactic co-ordinates were 1 mm behind, 2 mm lateral, 3.5 mm deep to the bregma. The injection was done using an insulin syringe, connected via a flexible tubing to a blunted metal cannula. The cannula was kept in place for a further 5 minutes to prevent reflux of blood. After this period the cannula was gently withdrawn and the entry hole sealed with bone wax.

Animals were returned to individual cages and allowed recover from anesthesia. Animals that survived for 8 weeks, post IVH were sacrificed and their brains removed and processed.

Results: The 1st rat which received the injection, developed opisthotonic posturing during the injection and died immediately, (? too rapid injection). 2 rats were found dead in their cages (day 1 and day 6, post IVH). Of the 5 rats that survived, 3 developed gait difficulty between the 2nd and 3rd weeks following surgery. They died between 4 and 6 weeks following IVH. Two rats survived 8 weeks, post IVH and were sacrificed.

Conclusion: 3 of 8 (38%) animals in this study developed difficulty with balance and gait 2 - 3 weeks post IVH. They did not have any obvious motor weakness. Post mortem brain examination of these animal revealed gross hydrocephalus (Only a thin cortical mantle was preserved). Post mortem brain examination of the two animals that survived 8 weeks post IVH, revealed moderate ventriculomegaly. We conclude that it is possible to reproduce PHVD following experimental IVH. The mortality rates were high. Controlled injection using motorized microinjectors may help reduce the mortality rates.

This study was undertaken in accordance with UK ethical guidelines.

1. Cherian S, Thoresen M, Silver IA, Whitelaw A, Love S. Transforming growth factor-betas in a rat model of neonatal posthaemorrhagic hydrocephalus. Neuropathol Appl Neurobiol. 2004 Dec;30(6):585-600.
2. Lodhia KR, Shakui P, Keep RF. Hydrocephalus in a rat model of intraventricular hemorrhage. Acta Neurochir Suppl. 2006;96:207-11.

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