Lidocaine attenuates cognitive impairment after isoflurane anesthesia in old rats

Abstract

Post-operative cognitive dysfunction (POCD) is a clinical phenomenon that has drawn significant attention from the public and scientific community. Age is a risk factor for POCD. However, the contribution of general anesthesia/anesthetics to POCD and the underlying neuropathology are not clear. Here, we showed that 18-month-old male Fisher 344 rats exposed to 1.2% isoflurane, a general anesthetic, for 2 h had significant learning and memory impairments assessed at 2 to 4 weeks after isoflurane exposure. These isoflurane effects were attenuated by intravenous lidocaine (1.5 mg/kg as a bolus and then 2 mg/kg/h during isoflurane exposure), a local anesthetic that has neuroprotective effect. Exposure to isoflurane or isoflurane plus lidocaine did not change the neuronal and synaptic density as well as the expression of NeuN (a neuronal protein), drebrin (a dendritic spine protein), synaptophysin (a synaptic protein), activated caspase 3 and caspase-activated DNase in the hippocampus at 29 days after isoflurane exposure when cognitive impairment was present. Isoflurane and lidocaine did not affect the amount of β-amyloid peptide, total tau and phospho-tau in the cerebral cortex as well as interleukin-1β and tumor necrosis factor-α in the hippocampus at 29 days after isoflurane exposure. Thus, isoflurane induces learning and memory impairment in old rats. Lidocaine attenuates these isoflurane effects. Isoflurane may not cause long-lasting neuropathological changes.

The Choice of General Anesthetics May Not Affect Neuroinflammation and Impairment of Learning and Memory After Surgery in Elderly Rats

“…We and others have shown that neuroinflammation may be the underlying pathology for cognitive impairment after surgery and anesthesia (Cibelli et al 2010;Terrando et al 2011;Cao et al 2012;Lin et al 2012;Vizcaychipi et al 2014;Zhang et al 2014a, b). Our current study showed that surgery induced an increase of inflammatory cytokines, such as IL-1β, and Iba-1, a marker for microglia and leukocytes.…”

“…Animal studies have shown that isoflurane alone can induce learning and memory dysfunction and mild neuroinflammation Cao et al 2012;Fidalgo et al 2012;Zuo 2012). Neuroinflammation may be the underlying neuropathology for POCD (Cibelli et al 2010;Terrando et al 2011;Cao et al 2012;Lin et al 2012). Thus, it is possible that volatile anesthetics may contribute to the development of POCD.…”

Postoperative Cognitive Effects in Newborns

“…4,5 This finding is consistent with previous studies showing that neuroinflammation is associated with cognitive impairment in humans [7][8][9] and in animals [10][11][12] and that neuroinflammation may contribute to cognitive impairment after isoflurane anesthesia or isoflurane anesthesia plus surgery in adult animals. 10,[12][13][14] it is proposed that perioperative neuroinflammation plays an important role in postoperative cognitive dysfunction and therefore, the resolution of this neuroinflammation after surgery may result in cognitive improvement in adults. 15 Xie's studies extend this detrimental role of neuroinflammation in cognitive impairment to developing brains.…”

“…However, lidocaine, a local anesthetic with antiinflammatory property, has been shown to reduce isoflurane-induced cognitive impairment and brain expression of inflammatory cytokines in adult animals. 13,14 lidocaine has been commonly used clinically during general anesthesia and may be an alternative for ketorolac to reduce cognitive impairment in the developing brain should its effectiveness be established in the future studies.…”

Neuroinflammation and Postoperative Cognitive Dysfunction: What Do We Know?

“…Therefore, immune modulatory therapy should be considered carefully and is currently still in its infancy in clinical practice. Lidocaine has been commonly used in clinical practice during general anesthesia with anti-inflammatory properties and may be an alternative for the immune modulatory therapies to reduce POCD (34). Furthermore, proper modulation of endogenous anti-inflammatory and proresolving pathways may have the therapeutic potential for preventing/reducing POCD and possibly other perioperative and neurodegenerative conditions (18,35,36).…”