Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents

Abstract

The most important aspect of a preclinical study seeking to develop a novel therapy for neurological diseases is whether the therapy produces any clinically relevant functional recovery. For this purpose, neurobehavioral tests are commonly used to evaluate the neuroprotective efficacy of treatments in a wide array of cerebrovascular diseases and neurotrauma. Their use, however, has been limited in experimental subarachnoid hemorrhage studies. After several randomized, double-blinded, controlled clinical trials repeatedly failed to produce a benefit in functional outcome despite some improvement in angiographic vasospasm, more rigorous methods of neurobehavioral testing became critical to provide a more comprehensive evaluation of the functional efficacy of proposed treatments. While several subarachnoid hemorrhage studies have incorporated an array of neurobehavioral assays, a standardized methodology has not been agreed upon. Here, we review neurobehavioral tests for rodents and their potential application to subarachnoid hemorrhage studies. Developing a standardized neurobehavioral testing regimen in rodent studies of subarachnoid hemorrhage would allow for better comparison of results between laboratories and a better prediction of what interventions would produce functional benefits in humans.

Keywords: Animal models; behavior (rodent); cognitive impairment; experimental; subarachnoid hemorrhage.

Figure 1.

Results of SAH studies using neurological scoring within 72 h in mice. (+ sign denotes list of studies with positive results, − sign denotes list of studies with negative results).

Figure 2.

Results of SAH studies using neurological scoring within 72 h in rats. (+ sign denotes list of studies with positive results, − sign denotes list of studies with negative results).