Do statins reduce the risk of aneurysm development? A case-control study.

OBJECT: Recent studies in rats have demonstrated that statins may have an inhibitory effect on intracranial aneurysm (IA) development. The purpose of this study was to assess whether long-term statin use is associated with a reduced risk of IA formation in humans. METHODS: This was a single-center case-control study that included consecutive patients admitted to the authors' institution between January 1, 2005, and December 31, 2008. A case was defined as a patient with a cerebral angiography-confirmed diagnosis of IA. Three controls were matched to each case based on age, sex, and index year of hospital admission. The primary exposure of interest was cumulative statin use. Conditional logistic regression was used to assess the relationship between statin intake and incidence of IA. RESULTS: In total, 1200 patients were included in the study. No overall association was found between statin use and incidence of IA formation (OR 1.08, 95% CI 0.69-1.69), nor when dichotomized into hydrophilic and lipophilic user, or between short (≤ 12-month) and long (≥ 36-month) duration of intake. Hypertension and smoking significantly increased the risk of IA development (OR 4.02, 95% CI 2.49-6.45, and OR 1.67, 95% CI 1.02-2.72, respectively). CONCLUSIONS: In contrast to recent experimental reports of the association between statins and a reduction of IA formation, the authors' findings suggest that in humans statins may have no significant beneficial effect on IA suppression.

Preliminary results of an ICP-controlled subarachnoid hemorrhage rabbit model for the study of delayed cerebral vasospasm.

INTRODUCTION: Intracisternal blood injection is the most common applied experimental subarachnoid bleeding technique in rabbits. The model comprises examiner-dependent variables and does not closely represent the human pathophysiological sequelae of ruptured cerebral aneurysm. The degree of achieved delayed cerebral vasospasm (DCVS) in this model is often mild. The aim of this study was to characterize and evaluate the feasibility of a clinically more relevant experimental SAH in vivo model. SAH was performed by arterial blood shunting from the subclavian artery into the great cerebral cistern. A total of five experiments were performed. Intracranial pressure (ICP), arterial blood pressure, heart rate, arterial blood gas analysis, and neurological status were monitored throughout the experiments. SAH induced vasoconstriction of the basilar artery was 52.1±3.4% on day 3 compared to baseline (P<0.05). Post-mortem gross examination of the brain showed massive blood clot accumulation around the brainstem and ventral surface of the brain. The novel technique offers an examiner independent SAH induction and triggers high degrees of delayed cerebral vasospasm. The severity of vasospasm attained offers a unique opportunity to evaluate future therapeutic treatment options.

Extra-intracranial blood shunt mimicking aneurysm rupture: intracranial-pressure-controlled rabbit subarachnoid hemorrhage model.

INTRODUCTION: The achieved degree of delayed cerebral vasospasm (DCVS) in the rabbits most frequently applied cistern magna blood injection model is often mild. The aim of this study was to characterize and evaluate the feasibility of an experimental SAH technique that mimics pathophysiological mechanisms and triggers higher degrees of DCVS. MATERIALS AND METHODS: SAH was induced by extracranial-intracranial (EC/IC) shunting of blood from the subclavian artery into the great cerebral cistern. Intracranial pressure (ICP), arterial blood pressure, heart rate, arterial blood gas analysis, and neurological status were monitored throughout the experiments. The magnitude of spasm was determined by comparison of pre-SAH (day 0) and post-SAH (day 3) angiograms and postmortem morphometric analysis of the basilar artery. RESULTS: A total of 13 experiments (SAH, n=11; controls, n=2) were performed. Two animals died after initiation of the EC/IC blood shunt in respiratory arrest. In SAH animals, ICP (baseline: 12+/-1 [mean+/-SD]; peak: 51+/-4; steady-state level: 15+/-2 mm Hg) rose to diastolic blood pressure levels (56+/-3 mm Hg) within 98+/-20s, and fell to a steady state within 186+/-41 s. SAH-induced vasoconstriction of the basilar artery was 53.1+/-2.8% on day 3 compared to baseline (P<0.05) and histology confirmed marked vasoconstriction. CONCLUSIONS: This novel technique of SAH induction closely mimics the pathophysiological sequelae of aneurysm rupture and triggers constant higher degrees of delayed cerebral vasospasm than previously described rabbit models. The severity of vasospasm attained offers a unique opportunity to evaluate future therapeutic treatment options.

Creatine treatment promotes differentiation of GABA-ergic neuronal precursors in cultured fetal rat spinal cord.

Creatine is a substrate of cytosolic and mitochondrial creatine kinases. Its supplementation augments cellular levels of creatine and phosphocreatine, the rate of ATP resynthesis, and improves the function of the creatine kinase energy shuttle. High cytoplasmatic total creatine levels have been reported to be neuroprotective by inhibiting apoptosis. In addition, creatine has direct antioxidant effects, which may be of importance in amyotrophic lateral sclerosis. In the present study, we investigated the effects of creatine [5 mM] on survival and differentiation of cultured GABA-immunoreactive (-ir) and choline acetyltransferase (ChAT)-ir rat spinal cord neurons. Furthermore, we addressed the neuroprotective potential of creatine supplementation against 3-nitropropionic acid (3-NP) induced toxicity. General cell survival and total neuronal cell density were not altered by chronic creatine treatment. We found, however, after chronic creatine and short-term creatine exposure a significantly higher density of GABA-ir neurons hinting to a differentiation-inducing mechanism of creatine. This notion is further supported by a significant higher content of GAD after creatine exposure. Creatine supplementation also exerted a partial, but significant neuroprotection for GABA-ir neurons against 3-NP induced toxicity. Interestingly, chronic creatine treatment did not alter cell density of ChAT-ir neurons but promoted their morphologic differentiation. Cell soma size and number of primary neurites per neuron were increased significantly after creatine supplementation. Taken together, creatine supplementation promoted the differentiation or the survival of GABAergic neurons and resulted in partial neuroprotection against 3-NP induced toxicity. The data suggest that creatine may play a critical role during development of spinal cord neurons.