Background: General anesthesia has been associated with neuronal apoptosis and activation of caspases. Apoptosis is a crucial factor in early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). We conducted a double-blind, prospective, randomized pilot study to evaluate the effect of 4 anesthetic agents on cerebrospinal fluid (CSF) and serum caspase-3 levels in aSAH patients. Materials and Methods: A total of 44 good-grade aSAH patients with preoperative lumbar drain scheduled for surgical clipping or endovascular coiling were randomized to receive maintenance of anesthesia with propofol, isoflurane, sevoflurane, or desflurane. Caspase-3 levels were measured in CSF and serum samples collected at baseline, 1 hour after induction, and 1 hour after cessation of anesthesia. Results: Compared with baseline, there was a decrease in CSF caspase-3 levels and an increase in serum caspase-3 levels 1 hour after exposure to all 4 anesthetic agents; levels returned to baseline values after cessation of anesthesia. Median CSF caspase-3 levels at baseline, 1 hour after anesthesia exposure, and 1 hour after cessation of anesthesia were 0.0679, 0.0004, and 0.0689 ng/mL, respectively (P<0.05). Median serum caspase-3 levels at baseline, 1 hour after anesthesia exposure, and 1-hour after cessation of anesthesia were 0.0028, 0.0682, and 0.0044 ng/mL, respectively (P<0.05). Conclusions: Propofol, isoflurane, sevoflurane, or desflurane have similar effects on CSF and serum caspase-3. The reduction of intraoperative CSF caspase-3 levels suggests a possible role for general anesthesia in neuroresuscitation by slowing the neuronal apoptotic pathway.

Background: For maintenance of anesthesia for intracranial aneurysmal neck clipping, both intravenous and inhalational anesthetics are in vogue. We aimed to evaluate the superiority of one agent over the other for long-term neurological outcomes in these patients. Methods: This prospective assessor-blind randomized study was conducted in 106 patients of 18–65 years of age with World Federation of Neurosurgeons Grade I-II of subarachnoid hemorrhage. After written informed consent, the patients were randomized into – intravenous group (Propofol) and inhalational group (Desflurane). The primary outcome was to study neurological outcome using Glasgow outcome scale (GOS) at 3 months following discharge while secondary outcomes included intraoperative brain condition, intraoperative hemodynamics, duration of hospital stay, Modified Rankin Score (MRS) at discharge, MRS, and Barthel’s index at 3 months following discharge and estimation of perioperative biomarkers of brain injury. Results: The GOS at 3 months was 5 (5.00–5.00) in the propofol group and 5 (4.00–5.00) in the desflurane group (P = 0.24). Both the anesthetics were similar in terms of intraoperative hemodynamics, brain relaxation, duration of hospital stay, MRS at discharge and 3 months, and Barthel Index at 3 months (P > 0.05). The perioperative serum interleukin-6 and S100B were comparable among the groups (P > 0.05). Conclusion: The long-term neurological outcome of good grade aneurysm patients undergoing craniotomy and clipping remains comparable with the use of either propofol or desflurane. The effect of the two anesthetic agents on the various clinical parameters and the biomarkers of brain injury is also similar.

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The scientific basis of intracranial aneurysm (IA) formation, its rupture and further development of cerebral vasospasm remains incompletely understood. Deciphering the molecular mechanisms underlying these events will lead to identification of early detection biomarkers and in turn, improved treatment outcomes. Aberrant protein expression may drive structural alterations of vasculature found in IA. To unravel these aberrations, we performed untargeted, global, quantitative proteomic analysis of aneurysm tissue and serum from patients with IA. Samples were derived from patients of three clinical sub groups-1) unruptured aneurysm 2) ruptured aneurysm without vasospasm 3) ruptured aneurysm who developed vasospasm. A total of 937 and 294 proteins were identified in aneurysm tissue and serum samples respectively. Several proteins that are known to maintain the structural integrity of vasculature were found to be dysregulated. ORM1, a glycoprotein, was significantly upregulated in both the aneurysm tissue and serum samples of unruptured IA patients. We employed a larger cohort of patients and validated ORM1 as a potential biomarker for screening of unruptured aneurysm using ELISA. Samples from ruptured aneurysm with vasospasm showed significant upregulation of MMP9 as compared to ruptured aneurysm without vasospasm. Using a cohort of ruptured aneurysm patients with and without vasospasm, we validated MMP9 as a potential biomarker for vasospasm. This study reveals pathophysiology underlying different clinical sub groups of IA and also suggests potential biomarkers.

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