Isoflurane on brain inflammation

Abstract

Brain inflammation may play an important role in the pathophysiology of early brain injury after subarachnoid hemorrhage (SAH). Our aim was to demonstrate brain inflammation development and to determine whether isoflurane, a clinically available volatile anesthetic agent, prevents brain inflammation after SAH. This study used 162 8-week-old male CD-1 mice. We induced SAH with endovascular perforation in mice and randomly assigned animals to sham-operated (n=21), SAH+vehicle-air (n=35) and SAH+2% isoflurane (n=31). In addition to evaluation of brain injury (neurological scores, brain edema and Evans blue dye extravasation), brain inflammation was evaluated by means of expression changes in markers of inflammatory cells (ionized calcium binding adaptor molecule-1, myeloperoxidase), cytokines (tumor necrosis factor [TNF]-α, interleukin-1β), adhesion molecules (intercellular adhesion molecule [ICAM]-1, P-selectin), inducers of inflammation (cyclooxygenase-2, phosphorylated c-Jun N-terminal kinase [p-JNK]) and endothelial cell activation (von Willebrand factor) at 24 hours post-SAH. Sphingosine kinase inhibitor (N, N-dimethylsphingosine [DMS]) and sphingosine-1-phosphate receptor-1/3 antagonist (VPC23019) were used to block isoflurane’s effects (n=22, each). SAH caused early brain injury, which was associated with inflammation so that all evaluated markers of inflammation were increased. Isoflurane significantly inhibited both brain injury (P<0.001, respectively) and inflammation (myeloperoxidase, P=0.022; interleukin-1β, P=0.002; TNF-α, P=0.015; P-selectin, P=0.010; ICAM-1, P=0.016; p-JNK, P<0.001; cyclooxygenase-2, P=0.003, respectively). This beneficial effect of isoflurane was abolished with DMS and VPC23019. Isoflurane may suppress post-SAH brain inflammation possibly via the sphingosine-related pathway.

Isoflurane prevents acquired epilepsy in rat models of temporal lobe epilepsy

“…4,39,42,43 Furthermore, it is thought that activation of the brain-derived neurotrophic factor (BDNF) receptor, tropomyosin receptor kinase B (TrkB), is required for brain insult-induced epileptogenesis. 46 Furthermore, isoflurane blocks glutamatergic excitation, potentiates gammaaminobutyric acid, and exerts anti-inflammatory, antioxidative, antiapoptotic, and neuroprotective effects, 12,47,48 all of which may be relevant for the antiepileptogenic activity reported here. 46 Furthermore, isoflurane blocks glutamatergic excitation, potentiates gammaaminobutyric acid, and exerts anti-inflammatory, antioxidative, antiapoptotic, and neuroprotective effects, 12,47,48 all of which may be relevant for the antiepileptogenic activity reported here.…”

“…44,45 Isoflurane has been reported to downregulate the BDNF-TrkB signaling pathway by an epigenetic effect. 46 Furthermore, isoflurane blocks glutamatergic excitation, potentiates gammaaminobutyric acid, and exerts anti-inflammatory, antioxidative, antiapoptotic, and neuroprotective effects, 12,47,48 all of which may be relevant for the antiepileptogenic activity reported here. With respect to endothelial cell integrity, contradicting findings 49,50 may reflect the tested preparation and dose and duration of isoflurane anesthesia.…”

“…52,53 Experiments in a TBI model in rats in which different anesthetic and sedative agents, including propofol and ketamine, were administered early after injury showed that rats treated with isoflurane had the best cognitive recovery and hippocampal neuronal survival. 48 Only few previous studies succeeded in discovering therapies that prevent epilepsy in rodent models. 56 The mechanisms underlying the BBBprotecting effect of isoflurane are not known, but could be attributed to its capacity to inhibit calcium influx into endothelial cells, 57,58 reduce adhesion of neutrophils to endothelial cells, 59,60 preserve tight junction expression, 61 and inhibit neuroinflammation.…”

“…56 The mechanisms underlying the BBBprotecting effect of isoflurane are not known, but could be attributed to its capacity to inhibit calcium influx into endothelial cells, 57,58 reduce adhesion of neutrophils to endothelial cells, 59,60 preserve tight junction expression, 61 and inhibit neuroinflammation. 48 Only few previous studies succeeded in discovering therapies that prevent epilepsy in rodent models. Liu et al 45 reported that inhibition of TrkB after SE induced by intra-amygdalar kainate injection in mice inhibits epileptogenesis.…”

New Grading System Based on Magnetic Resonance Imaging in a Mouse Model of Subarachnoid Hemorrhage

“…Neurological scores were also evaluated at 24 hours after SAH by a blinded observer as previously described. 8 Mice were given a score of 3 to 18 in 1-number steps (higher scores indicate greater function).…”