Animal models for intracranial pressure monitoring in traumatic brain injury.

Abstract

The aim of this study was to identify appropriate animal models of raised intracranial pressure (ICP) and brain tissue oxygenation (P[subscript]btO₂) following traumatic brain injury (TBI) that would be suitable for the development of novel therapies for secondary brain injury. Monitoring of ICP and P[subscript]btO₂ are important for understanding the effects of altered cerebral perfusion pressure (CPP). Tissue oxygenation is determined by the interaction of these variables and is important in the prevention of secondary injury following TBI. Unfortunately, few animal models reproduce the ICP and P[subscript]btO₂ response that has been observed in the human condition. Previous studies at the University of Adelaide have used an ovine model of TBI in which the neuropathological response in these animals accurately mimics human TBI. However functional studies using sheep, at present are problematic. Development of an alternative small animal model with scope for functional studies would assist with development of clinical therapies. Aside from rats, which do not exhibit profound increases in ICP without the presence of a significant mass lesion, guinea pigs have been successfully used previously in studies of TBI. We therefore compared the ICP and P[subscript]btO₂ response in guinea pigs with those of sheep. Compared to sheep, the guinea pig proved unsuitable for the study of ICP. Their labile response to inhalational anaesthesia, which included significant hypotension and bradycardia, was a confounding factor. With careful review and alteration to the anaesthetic regime, this problem was reduced, albeit that reproducible increases in ICP were never shown after TBI. Although the reasons for a lack of ICP response in guinea pigs and rats are unknown, we note that sheep have a higher tentorial index than both species, and that the presence of an intact tentorium may restrict increases in pressure to a single compartment, thus increasing ICP. We propose that species with higher tentorial indexes may prove to be a more suitable than rodents for the study of ICP and functional outcome after TBI.