Sevoflurane and Desflurane Exposures Following Aneurysmal Subarachnoid Hemorrhage Confer Multifaceted Protection against Delayed Cerebral Ischemia

Abstract

Numerous studies have demonstrated the ability of isoflurane conditioning to provide multifaceted protection against aneurysmal subarachnoid hemorrhage (SAH)-associated delayed cerebral ischemia (DCI); however, preclinical studies have not yet examined whether other commonly used inhalational anesthetics in neurological patients such as sevoflurane or desflurane are also protective against SAH-induced neurovascular deficits. We therefore sought to identify the potential for sevoflurane and desflurane conditioning to protect against DCI in an endovascular perforation mouse model of SAH. Neurological function was assessed daily via neuroscore. Large artery vasospasm and microvessel thrombosis were assessed three days after SAH or sham surgery. Four groups were examined: Sham, SAH + room air, SAH + 2% Sevoflurane, and SAH + 6% Desflurane. For the SAH groups, one hour after surgery, mice received 2% sevoflurane, 6% desflurane, or room air for one hour. We found that conditioning with sevoflurane or desflurane attenuated large artery vasospasm, reduced microvessel thrombosis, and improved neurologic function. Given their frequent clinical use and strong safety profile in patients (including those with SAH), these data strongly support further studies to validate these findings in preclinical and clinical studies and to elucidate the mechanisms by which these agents might be acting.

Conditioning-based therapeutics for aneurysmal subarachnoid hemorrhage – A critical review

“…Numerous preclinical studies from independent laboratories have shown volatile anesthetics provide robust protection against EBI and DCI leading to improved short-term neurological deficits in rodent models of SAH. 37,38,[43][44][45][46][47][48][60][61][62][63][64][65][66] Several observational cohort studies in SAH patients corroborate these experimental results. [71][72][73][74][75][76] Regarding underlying mechanisms for the demonstrated neurovascular protection, most work has concentrated on isoflurane conditioning 37,38,[62][63][64] however, much less is known regarding the underlying mechanisms for the more commonly used volatile anesthetics such as sevoflurane and desflurane -a topic that deserves further investigation.…”

“…1 MAC) of sevoflurane (2%) and desflurane (6%) also provided significant DCI protection in an endovascular perforation mouse model of SAH. 66 Finally, we recently examined the impact of intravenous anesthetic conditioning in SAH to begin to examine whether different anesthetic classes have differing effects on DCI. In contradistinction to various volatile inhalational anesthetics, intravenous administration of an anesthetic dose of propofol (2 mg/kg/min × 1 hr) did not afford any protection against vasospasm or the neurologic deficits in an endovascular perforation mouse model of SAH.…”

Isoflurane preconditioning induced genomic changes in mouse cortex

“…Supporting this notion, numerous studies have implicated a protective role of isoflurane preconditioning in several in vivo and in vitro brain injury models, including ischaemic stroke, spinal cord injury, hypoxic ischaemic brain injury, and oxygen glucose deprivation injury models. 12 , 13 , 14 , 15 , 16 , 17 Interestingly, Gaidhani and colleagues, 20 using a common ischaemic stroke model (transient middle cerebral artery occlusion in rats) showed that isoflurane-induced neuroprotection was directly proportional to the duration of anaesthesia, suggesting that isoflurane anaesthesia for experimental procedures should be restricted to 20–30 min to avoid the confounding results during novel drug testing. Whether this duration applies to other animal/brain injury models and the molecular changes induced by isoflurane exposure (<1 h) remains to be investigated.…”

“… 6 , 7 , 8 , 9 , 10 , 11 Specifically, volatile anaesthetics (such as isoflurane, sevoflurane, and desflurane) have been shown to induce strong neuroprotection against several nervous system disorders. 12 , 13 , 14 , 15 , 16 These volatile anaesthetics are FDA approved, have an excellent safety profile in humans, and are used in millions of patients on a regular basis. Therefore, understanding the molecular foundations of volatile anaesthetic conditioning will identify new molecular targets for drug development and heighten the translational potential of anaesthetic conditioning-based therapeutics.…”

Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review

“…The choice of anesthetic agents can significantly influence (patho)physiology, with some substances even demonstrating neuroprotective properties following experimental SAH. 33 , 34 Notably, chloral hydrate was frequently used as the only substance for anesthesia induction in a significant number of studies. However, chloral hydrate does not provide sufficient analgesia in small animals; thus, its use as a sole agent should be omitted.…”