Simvastatin Administration Ameliorates Neurobehavioral Consequences of Subarachnoid Hemorrhage in the Rat

Abstract

In the present study we assessed the neuroprotective effects of simvastatin in a rodent model of experimental subarachnoid hemorrhage (SAH). Based on recent data showing the role of statins not only in lowering the level of cholesterol but also in preventing cardiac and cerebrovascular damage in risk population, and in decreasing vasospasm and delayed ischemia after aneurysmal SAH, we investigated the neuroprotective effects of intraperitoneal administration of simvastatin (40 mg/kg/day for 5 consecutive days) in Sprague-Dawley rats 30 min after SAH, as compared to vehicle-treated SAH animals. We employed a battery of well-characterized tests to assess memory, learning, motivational, balance, and behavioral performances. On days 1-4 post-SAH, simvastatin-treated rats have significantly improved beam balance scores (days 1-2, p<0.001; days 3-4, p<0.01), beam balance times (days 1-4, p<0.01), and latency to traverse the beam (days 1-3, p<0.01; day 2, p<0.005; day 4, p<0.0001) in comparison with control groups that, conversely, were not protected against SAH-related body weight changes. These results demonstrate that the administration of simvastatin may represent a beneficial therapeutic approach able to reduce post-SAH cognitive dysfunction.

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

“…[67][68][69] Beam traversing times were shown to be higher on days 1 to 4 after SAH induction in rats. [67][68][69] There were no significant differences in the beam walking test in an endovascular perforation model of SAH 3, 7, 14, and 21 days after SAH in rats; however, the parameter used (% impaired steps) was different from that used in the previous studies. 70 The beam balance test offers flexibility in measurements that can make experiments conducted in different laboratories difficult to compare.…”

Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm

“…Animal studies have demonstrated that statins may ameliorate early brain injury after experimental SAH 102 and improve neurocognitive outcomes. 103 To date, four prospective, randomized, placebo-controlled trials have been published evaluating the efficacy of statins in the prevention of DCI. These investigated a combined total of 190 patients with three of the studies trialling simvastatin 80 mg for 14-21 days 104 -106 and one study trialling pravastatin 40 mg for a maximum of 14 days.…”

Effect of statins on aneurysmal subarachnoid hemorrhage: a meta-analysis of randomized controlled trials

“…Atorvastatin can reduce the incidence and severity of CVS and suppress a biomarker of cerebral ischemia after aSAH (20). Simvastatin has a beneficial therapeutic effect on reducing cognitive dysfunction after aSAH (16). Clinical trials have demonstrated that simvastatin reduces CVS and mortality and improves functional outcomes, although these findings were not statistically significant (4).…”